The DOI matches its Crossref record; 269 of the 269 references it cites were found in a registry or an index; 94 of the 276 sources its claims cite were checked for support.
Atopic dermatitis: an expanding therapeutic pipeline for a complex disease
Open accessAbstract
Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a complex pathophysiology that underlies a wide spectrum of clinical phenotypes. AD remains challenging to treat owing to the limited response to available therapies. However, recent advances in understanding of disease mechanisms have led to the discovery of novel potential therapeutic targets and drug candidates. In addition to regulatory approval for the IL-4Ra inhibitor dupilumab, the anti-IL-13 inhibitor tralokinumab and the JAK1/2 inhibitor baricitinib in Europe, there are now more than 70 new compounds in development. This Review assesses the various strategies and novel agents currently being investigated for AD and highlights the potential for a precision medicine approach to enable prevention and more effective long-term control of this complex disease.
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80 No full text of the sources · 37 Partly supported · 37 Own interpretation · 31 No basis given · 21 Sources not found · 15 Supported · 12 Supported so far · 9 Own result · 3 Own method · 2 Couldn’t confirm · 2 Not checked yet · 1 Mixed support · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“S1P acts via gradients in circulatory fluids and has been reported to be increased in various conditions such as multiple sclerosis and neurodegeneration158, pneumonia159, psoriasis160, asthma161 and more recently in AD162.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Disputedcites [158] Alessenko, A. V. & Albi, E. Exploring sphingolipid implications in neurodegeneration. Front. Neurol. 11, 437 (2020). sourceExperimental — accuracy not yet measured
Citation 158 is attached to the multiple-sclerosis and neurodegeneration portion of the sentence, not to pneumonia, psoriasis, asthma, or AD. The Alzheimer's Disease section reports reduced S1P in a brain region of patients with AD, a neurodegenerative condition, rather than increased S1P. The Neurodegenerative Disorders section says sphingolipids change in these diseases but does not establish an S1P increase in multiple sclerosis (page numbers unavailable). (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
- Supportedcites [159] Hsu, S. C. et al. Circulating sphingosine-1-phosphate as a prognostic biomarker for community-acquired pneumonia. PLoS ONE 14, e0216963 (2019). source
Citation 159 is attached to the pneumonia example, not the other conditions in the sentence. The Discussion (page not provided) reports significantly increased plasma S1P in patients with community-acquired pneumonia compared with healthy controls. (LLM, conf=0.94)
- Partly supportedcites [160] Checa, A. et al. Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-alpha treatment. Sci. Rep. 5, 12017 (2015). sourceExperimental — accuracy not yet measured
Citation 160 is attached to psoriasis, not the other conditions listed. The Results report elevated circulating S1P in severe psoriasis compared with healthy controls, but no significant difference in mild psoriasis. The unqualified reference to psoriasis omits that limitation. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [161] Kim, S. H. et al. Ceramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma. Allergy 75, 1991–2004 (2020). source
- Not checked — no full text of the sourcecites [162] Sakai, T. et al. Serum sphingosine-1-phosphate is elevated in atopic dermatitis and associated with the severity and inflammation. Allergy https://doi.org/10.1111/all.14826 (2021). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Disputed
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“For practical purposes, disease severity remains the basis for the treatment algorithm in the current guidelines31–35.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Not checked — no full text of the sourcecites [31] Wollenberg, A. et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J. Eur. Acad. Dermatol. Venereol. 32, 657–682 (2018). source
- Not checked — no full text of the sourcecites [32] Wollenberg, A. et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J. Eur. Acad. Dermatol. Venereol. 32, 850–878 (2018). source
- Not checked — no full text of the sourcecites [33] Katayama, I. et al. Japanese guidelines for atopic dermatitis 2017. Allergol. Int. 66, 230–247 (2017). source
- Not checked — no full text of the sourcecites [34] Eichenfield, L. F. et al. Current guidelines for the evaluation and management of atopic dermatitis: a comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. J. Allergy Clin. Immunol. 139, S49–S57 (2017). source
- Supportedcites [35] Wollenberg, A. et al. ETFAD/EADV Eczema Task Force 2020 Position Paper on diagnosis and treatment of atopic dermatitis in adults and children. J. Eur. Acad. Dermatol. Venereol. 34, 2717–2744 (2020). sourceExperimental — accuracy not yet measured
The treatment figure (p. 6) explicitly describes its recommendations for adults and children as based on disease severity. The adult treatment algorithm (p. 6) then assigns different options to mild, moderate, and severe disease. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“whereas baricitinib exemplifies a more wide-ranging approach using small molecules17 that interact with multiple signal transduction pathways linked to several cytokine receptors and immune pathways.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Introduction
What the sources say
- Supportedcites [17] Schwartz, D. M. et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat. Rev. Drug Discov. 16, 843–862 (2017). Excellent review on the mode of action of JAK inhibitors. source
The baricitinib discussion (page unavailable) identifies it as an inhibitor of JAK1 and JAK2. The Abstract (page unavailable) explains that JAK inhibitors are small molecules acting on signaling mediators downstream of many pro-inflammatory cytokines, supporting the cited description of a wide-ranging approach. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The sequential and/or cumulative immunological events that underlie the complex clinical phenotype are key to understanding the value of targeted therapies for distinct pathways such as TH2, TH17 and/or TH22 response124,125.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Supportedcites [124] Czarnowicki, T. et al. Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. J. Allergy Clin. Immunol. 145, 215–228 (2020). source
The Discussion (page unavailable) describes progressive, age-related immune endotypes in atopic dermatitis and says profiling them is imperative for targeted therapeutic development. It links varied immune polarizations, including Th2 activation and increasing IL-22, to the need for treatments tailored to those endotypes. (LLM, conf=0.88)
- Partly supportedcites [125] Renert-Yuval, Y. et al. The molecular features of normal and atopic dermatitis skin in infants, children, adolescents and adults. J. Allergy Clin. Immunol. 148, 148–163 (2021). sourceExperimental — accuracy not yet measured
The Results describe age-related differences in TH2, TH17 and TH22 markers, and the Discussion says these differences may inform the choice of targeted treatment. The paper does not establish sequential or cumulative immunological events underlying the clinical phenotype, or the value of therapies targeting each of the three pathways; it says the treatment implications require age-specific clinical trials. (LLM, conf=0.82)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mutations or variants of genes such as SPINK5 favour the generation of allergen-independent, nonspecific inflammation, providing a pro-T helper 2 (TH2) micromilieu by virtue of keratinocyte-derived alarmins such as thymic stromal lymphopoietin (TSLP), IL-33 and IL-25 (refs52,64).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Partly supportedcites [52] Briot, A. et al. Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J. Exp. Med. 206, 1135–1147 (2009). sourceExperimental — accuracy not yet measured
The Discussion (Figure 8; page unavailable) describes SPINK5 deficiency as initiating inflammation independently of environmental factors and creating a pro-Th2 microenvironment through keratinocyte-derived TSLP. The cited paper does not identify IL-33 or IL-25 as mediators of that pathway, so it supports only part of the attributed claim. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [64] Hammad, H. & Lambrecht, B. N. Barrier epithelial cells and the control of type 2 immunity. Immunity 43, 29–40 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Etokimab inhibited direct, as well as CXCR1-dependent, neutrophil migration in vitro.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Supportedcites [68] Chen, Y. L. et al. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci. Transl Med. 11, eaax2945 (2019). source
In the section on IL-33-induced neutrophil migration (page unavailable), etokimab significantly reduced migration toward IL-33 in a transwell assay. The CXCR1 section (page unavailable) reports that etokimab inhibited CXCR1 expression, reducing neutrophil sensitivity to IL-8 and migration toward it. These laboratory assays support the cited paraphrase. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
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In the paper
“Interestingly, this improvement lasted for up to 140 days after the single dose.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Partly supportedcites [68] Chen, Y. L. et al. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci. Transl Med. 11, eaax2945 (2019). sourceExperimental — accuracy not yet measured
The Efficacy section reports that clinical improvement after a single dose was sustained through day 57, but does not report that it lasted to day 140. Day 140 appears in the Pharmacodynamics section for an IgE measurement, not a clinical improvement outcome. Page numbers were unavailable in our copy. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“As one of the first and most important mediators in antigen presentation and induction of the inflammatory cascade, IL-1α has been considered as a therapeutic target in AD69.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Supportedcites [69] Archer, N. K. et al. Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1alpha release. J. Allergy Clin. Immunol. 143, 1426–1443 (2019). source
The Results section ('IL-1α is necessary for inducing chronic skin inflammation'; page unavailable) reports that neutralizing IL-1α reduced inflammation in filaggrin-deficient mice. The Discussion connects this IL-1α-driven mechanism to atopic dermatitis, supporting its consideration as a potential therapeutic target, though the paper does not establish a treatment for patients. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The anti-TSLP antibody tezepelumab (AMG 157) has shown convincing results in patients with severe and uncontrolled allergic asthma65,66.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Partly supportedcites [65] Menzies-Gow, A. et al. DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir. Res. 21, 279 (2020). sourceExperimental — accuracy not yet measured
The Background (page unavailable) reports that tezepelumab significantly reduced exacerbations and improved other outcomes in patients with severe, uncontrolled asthma. It does not identify those patients as having allergic asthma or report results specifically for that subgroup. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [66] Mullard, A. Tezepelumab prepares to enter the asthma antibody fray. Nat. Rev. Drug Discov. 20, 91 (2021). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
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In the paper
“Interestingly, in a mouse model, colonization with S. aureus induces IL-36R- and IL-1R-dependent inflammation73.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Partly supportedcites [73] Liu, H. et al. Staphylococcus aureus epicutaneous exposure drives skin inflammation via IL-36-mediated T cell responses. Cell Host Microbe 22, 653–666 (2017). Report on the direct impact of the microbiome on inflammation via the IL-36 pathway. sourceExperimental — accuracy not yet measured
In the Results section on IL-36R signaling (page unavailable), mice lacking IL-36R had substantially less skin inflammation after epicutaneous S. aureus exposure, supporting IL-36R dependence. The IL-1R-dependent part is not supported: mice lacking either IL-1α or IL-1β had inflammation measures similar to controls, and the paper distinguishes this epicutaneous response from the IL-1β response to intradermal infection. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“encouraging results were seen in patients with severe forms (SCORAD >50) where the mean decline in SCORAD was significantly better than in the placebo group122.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [122] Guttman-Yassky, E. et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: a randomized, double-blind, phase 2a trial. J. Am. Acad. Dermatol. 78, 872–881 (2018). source
The Results (Efficacy) report a significantly greater mean SCORAD decline with fezakinumab than placebo in the severe AD subgroup at weeks 12 and 20. The paper defines that subgroup as baseline SCORAD ≥50, while the citing sentence writes >50. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“after re-randomization at week 16 followed by maintenance treatment, the clinical response further improved, with IGA 0/1 being reached in 51% (ECZTRA1) and 59% (ECZTRA2) of the patients92.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [92] Wollenberg, A. et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br. J. Dermatol. 184, 437–449 (2020). sourceExperimental — accuracy not yet measured
The Results (Maintenance outcomes at week 52) report IGA 0 or 1 in 51% of ECZTRA 1 patients and 59% of ECZTRA 2 patients who continued tralokinumab every two weeks after rerandomization. These percentages describe maintenance of response among patients who had already achieved IGA 0 or 1 at week 16, not a further improvement among patients generally. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
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In the paper
“there is increasing evidence that the IL-23–IL-17 axis as well as IL-36 (see above) may have a role, at least in some AD subtypes such as the so-called intrinsic form and in Asian patients73,103,117,123–125.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [73] Liu, H. et al. Staphylococcus aureus epicutaneous exposure drives skin inflammation via IL-36-mediated T cell responses. Cell Host Microbe 22, 653–666 (2017). Report on the direct impact of the microbiome on inflammation via the IL-36 pathway. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) links IL-36 signaling to IL-17-producing T-cell responses in a mouse model of S. aureus-induced skin inflammation and relates the findings to human atopic dermatitis. It does not establish a role for the IL-23–IL-17 axis or address intrinsic atopic dermatitis or Asian patients, so the subtype-specific claim is not supported by this paper. (LLM, conf=0.86)
- Partly supportedcites [103] Suarez-Farinas, M. et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J. Allergy Clin. Immunol. 132, 361–370 (2013). sourceExperimental — accuracy not yet measured
The Results and Discussion report stronger IL-17/Th17 and IL-23-related activity in intrinsic than extrinsic atopic dermatitis, supporting a possible role for that axis in the intrinsic subtype. The paper mentions IL-36 only in discussing a proposed mechanism drawn from psoriasis research; it does not establish a role for IL-36 in atopic dermatitis or address Asian patients. Page numbers were not available in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [117] Esaki, H. et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J. Allergy Clin. Immunol. 138, 1639–1651 (2016). source
- Not checked — no full text of the sourcecites [123] Noda, S. et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J. Allergy Clin. Immunol. 136, 1254–1264 (2015). The first report on TH17 immune polarization in Asian patients, questioning the dogma of the TH2 immune dominance in AD. source
- Partly supportedcites [124] Czarnowicki, T. et al. Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. J. Allergy Clin. Immunol. 145, 215–228 (2020). sourceExperimental — accuracy not yet measured
The Discussion reports an IL-17 signature in pediatric atopic dermatitis skin, providing limited support for a role for IL-17 in a subtype of the disease. It does not establish a role for the IL-23–IL-17 axis or IL-36, or address the intrinsic form or Asian patients; searches for those terms found no relevant passage. The cited copy provides no page numbers. (LLM, conf=0.78)
- Partly supportedcites [125] Renert-Yuval, Y. et al. The molecular features of normal and atopic dermatitis skin in infants, children, adolescents and adults. J. Allergy Clin. Immunol. 148, 148–163 (2021). sourceExperimental — accuracy not yet measured
The Results and Discussion report elevated IL-17 and other TH17-related markers in atopic dermatitis, particularly in infants, supporting a possible role for that pathway. The passages do not establish a role for IL-36 or address the specified intrinsic and Asian patient subtypes; searches for those terms did not find relevant passages. The cited paper studies age groups rather than those subtypes. (LLM, conf=0.82)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“When considering the entire study population, there was no significant difference in the change of SCORAD compared with baseline as the primary end point.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [122] Guttman-Yassky, E. et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: a randomized, double-blind, phase 2a trial. J. Am. Acad. Dermatol. 78, 872–881 (2018). source
The Methods (Efficacy evaluations) identify change in SCORAD from baseline at week 12 as the primary endpoint. The Results (Efficacy) report that, for the entire study population, the difference in SCORAD reduction between fezakinumab and placebo at week 12 was not statistically significant (p=0.134). (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Whereas IL-4 seems to be more relevant for the central part of the TH2 pathway87”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [87] Bao, K. & Reinhardt, R. L. The differential expression of IL-4 and IL-13 and its impact on type-2 immunity. Cytokine 75, 25–37 (2015). Important paper explaining the different roles and impacts of IL-4 and IL-13 within the TH2 immune response and inflammation. source
In “Two distinct arms of type-2 inflammation and their therapeutic implications” (page unavailable), the paper associates IL-4-producing follicular T cells with the humoral arm of type-2 immunity and IL-13-producing Th2 cells with peripheral inflammation. That supports the hedged description of IL-4 as more relevant to the central, rather than peripheral, aspect of the pathway. (LLM, conf=0.88)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“IL-13 has been identified as the key TH2 cytokine mediating the skin inflammation in AD88,89.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [88] Tsoi, L. C. et al. Atopic dermatitis is an IL-13-dominant disease with greater molecular heterogeneity compared to psoriasis. J. Invest. Dermatol. 139, 1480–1489 (2019). source
The Results section identifies IL13 as the most distinctive Th2 marker for AD and says the findings suggest AD is an IL-13– rather than IL-4–driven disease. The Discussion also attributes much of the IL-4 response signature in AD skin to excess IL-13. The supplied passages do not give page numbers. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [89] Bieber, T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis. Allergy 75, 54–62 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“clinical improvement was shown in a small series of patients using omalizumab and/or immunoadsorption109–112.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [109] Zink, A. et al. Targeting IgE in severe atopic dermatitis with a combination of immunoadsorption and omalizumab. Acta Derm. Venereol. 96, 72–76 (2016). source
The paper reports a pilot study of 10 patients who received immunoadsorption followed by omalizumab (Immunoadsorption and omalizumab, p. 1; IgE during omalizumab and follow-up, p. 2). It reports clinical improvement during treatment, while noting the small sample and open-label design (Discussion, p. 4). (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [110] Hotze, M. et al. Increased efficacy of omalizumab in atopic dermatitis patients with wild-type filaggrin status and higher serum levels of phosphatidylcholines. Allergy 69, 132–135 (2014). source
- Not checked — no full text of the sourcecites [111] Lane, J. E., Cheyney, J. M., Lane, T. N., Kent, D. E. & Cohen, D. J. Treatment of recalcitrant atopic dermatitis with omalizumab. J. Am. Acad. Dermatol. 54, 68–72 (2006). source
- Not checked — no full text of the sourcecites [112] Holm, J. G., Agner, T., Sand, C. & Thomsen, S. F. Omalizumab for atopic dermatitis: case series and a systematic review of the literature. Int. J. Dermatol. 56, 18–26 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a phase IIb dose-finding study, the best clinical response for the primary end point (percentage change in EASI) was obtained with 250 mg. In this group, 72% improvement was shown versus 41% in the placebo group96.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [96] Guttman-Yassky, E. et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial. JAMA Dermatol. 156, 411–420 (2020). source
The Methods (Study Design) identify this as a phase 2b dose-ranging trial. Results (Primary End Point, Table 2) show the largest EASI improvement with lebrikizumab 250 mg every 2 weeks: 72.1% from baseline, compared with 41.1% for placebo. The claim rounds these values to 72% and 41%. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“IL-22 is an important part of the transcriptomic signature in AD116,117.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [116] Nograles, K. E. et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J. Allergy Clin. Immunol. 123, 1244–1252 (2009). source
The Results section reports that IL-22 mRNA was significantly upregulated in AD lesions compared with normal skin. The Discussion also describes an increased IL-22 signal as part of the immune profile of chronic AD. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [117] Esaki, H. et al. Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin. J. Allergy Clin. Immunol. 138, 1639–1651 (2016). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“as shown in vitro and in animal models154,155, has an important role in TH2-mediated inflammation of AD by directing their migration into the skin.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [154] Boehme, S. A. et al. A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. Int. Immunol. 21, 81–93 (2008). source
- Partly supportedcites [155] He, R. et al. The prostaglandin D(2) receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge. J. Allergy Clin. Immunol. 126, 784–790 (2010). sourceExperimental — accuracy not yet measured
The Introduction reports CRTH2-mediated chemotaxis in vitro, and the Results section on acute OVA challenge reports reduced skin infiltration by CD4+ cells and eosinophils in CRTH2-deficient mice (page numbers unavailable). But the Results on repeated sensitization find no important role for CRTH2 in chronic skin inflammation. The evidence therefore supports migration-related inflammation in an acute mouse model, not an unqualified role in AD inflammation. (LLM, conf=0.86)
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A maximal-use phase II study in Japanese children and adolescents confirmed the good safety and tolerance profile of this compound135.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [135] Saeki, H., Baba, N., Oshiden, K., Abe, Y. & Tsubouchi, H. Phase 2, randomized, double-blind, placebo-controlled, 4-week study to evaluate the safety and efficacy of OPA- 15406 (difamilast), a new topical selective phosphodiesterase type-4 inhibitor, in Japanese pediatric patients aged 2-14 years with atopic dermatitis. J. Dermatol. 47, 17–24 (2020). sourceExperimental — accuracy not yet measured
The Methods (Study design; page unavailable) describe a randomized, vehicle-controlled phase 2 study in Japan, not a maximal-use study. The Discussion (page unavailable) reports no serious treatment-emergent adverse events and suggests a favorable safety profile. The Introduction (page unavailable) attributes the maximal-use finding to a separate study conducted in the USA, so the claim conflates the two studies. (LLM, conf=0.90)
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“PDE4 inhibitors are known to have a wide spectrum of interesting therapeutic effects related to downregulation of inflammatory cytokines involved in pulmonary, neurological, rheumatoid, gastrointestinal and dermatological disorders128.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [128] Li, H., Zuo, J. & Tang, W. Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Front. Pharmacol. 9, 1048 (2018). source
The Introduction identifies PDE4 inhibition as a therapeutic strategy for airway, skin, bowel, rheumatoid and neuroinflammatory conditions. The “Mode of action” section describes its broad anti-inflammatory effects, including reduced pro-inflammatory cytokine production. The supplied passages do not give page numbers. (LLM, conf=0.90)
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- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Pilot open-label studies of this PDE4 inhibitor provided promising results129,130.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [129] Samrao, A., Berry, T. M., Goreshi, R. & Simpson, E. L. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch. Dermatol. 148, 890–897 (2012). source
The Design section identifies this as an open-label pilot study of apremilast. The Discussion reports clinically meaningful improvement and calls the results preliminary, consistent with describing them as promising. No page numbers are provided in the supplied passages. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [130] Volf, E. M., Au, S. C., Dumont, N., Scheinman, P. & Gottlieb, A. B. A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis. J. Drugs Dermatol. 11, 341–346 (2012).
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As neurons express receptors for IL-4 and IL-13, the early improvement of itch upon targeted therapy with dupilumab, tralokinumab or lebrikizumab supports the assumption of a direct effect of these drugs on nerve endings92,96,183.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Partly supportedcites [92] Wollenberg, A. et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br. J. Dermatol. 184, 437–449 (2020). sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports that itch improved as early as week 1 with tralokinumab versus placebo. The paper does not establish neuronal IL-4 or IL-13 receptor expression or infer a direct effect on nerve endings; it also does not report early itch outcomes for dupilumab or lebrikizumab. (LLM, conf=0.87)
- Supportedcites [96] Guttman-Yassky, E. et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial. JAMA Dermatol. 156, 411–420 (2020). source
The Discussion reports reduced itch by day 2 in the high-dose lebrikizumab group and says this is consistent with preclinical evidence that IL-13 directly sensitizes sensory neurons. This supports the citing sentence’s hedged inference about lebrikizumab; the other drugs are not the part this trial is cited to establish. (LLM, conf=0.85)
- Partly supportedcites [183] Simpson, E. L. et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N. Engl. J. Med. 375, 2335–2348 (2016). Reports on the pivotal studies that have led to the approval of dupilumab as the first-in-class biologic for the therapy of AD. sourceExperimental — accuracy not yet measured
The Measures of Pruritus section (p. 6) reports significantly better itching scores with dupilumab than placebo by week 2, and the Background (p. 2) says dupilumab inhibits IL-4 and IL-13 signaling. The paper does not establish that neurons express those receptors, assess tralokinumab or lebrikizumab, or propose a direct effect on nerve endings. (LLM, conf=0.89)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Neurons express receptors for IL-4 and IL-13.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Substance P is involved in the initiation and transmission of itch through the neurokinin 1 receptor (NK1R)195,196 and the Mas-related G protein-coupled receptor (MRGPRS)197,198 expressed in the central nervous system and on various other cell types.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Partly supportedcites [195] Steinhoff, M. S., von Mentzer, B., Geppetti, P., Pothoulakis, C. & Bunnett, N. W. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol. Rev. 94, 265–301 (2014). sourceExperimental — accuracy not yet measured
The review’s “Dermatitis and pruritus” section (p. 20) identifies substance P as a mediator of itch in atopic dermatitis, and “Sensory Disorders of Pain and Pruritus” (p. 26) reports that NK1R antagonism reduced scratching or itch in the studies discussed. Its “NKR activation in DRG and spinal cord” section (p. 21) describes NK1R on spinal neurons, but the passages found do not support the claim that substance P acts through MRGPRs to initiate or transmit itch. (LLM, conf=0.86)
- Partly supportedcites [196] Douglas, S. D. & Leeman, S. E. Neurokinin-1 receptor: functional significance in the immune system in reference to selected infections and inflammation. Ann. NY Acad. Sci. 1217, 83–95 (2011). sourceExperimental — accuracy not yet measured
The ‘Neurokinin 1 receptor’ section identifies NK1R as substance P’s preferred receptor and links their interaction to pain transmission. The ‘Substance P’ section reports substance P receptors on CNS cells. Neither passage establishes that the SP–NK1R pathway initiates or transmits itch; the separate MRGPRS citations are not attributed to this source. (LLM, conf=0.83)
- Partly supportedcites [197] Azimi, E. et al. Dual action of neurokinin-1 antagonists on Mas-related GPCRs. JCI Insight 1, e89362 (2016). sourceExperimental — accuracy not yet measured
The Discussion (p. 5) reports that substance P–mediated scratching in mice correlates with Mrgpr activation, and that Mrgprs are expressed on sensory neurons and mast cells. The paper does not establish the claim that these receptors transmit itch in the central nervous system; its expression evidence concerns dorsal root ganglion neurons and mast cells. (LLM, conf=0.85)
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“It signals through the heterodimerization of IL-31Rα and the oncostatin M receptor-β (OSMRβ)186,187.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Supportedcites [186] Jones, S. A. & Jenkins, B. J. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat. Rev. Immunol. 18, 773–789 (2018). source
The Figure 1 legend states that the IL-31 receptor consists of IL-31Rα and OSMRβ. The section ‘What constitutes IL-6 family membership?’ likewise describes IL-31 binding a receptor complex containing those two subunits. No page number is provided in our copy. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [187] Hermanns, H. M. Oncostatin M and interleukin-31: cytokines, receptors, signal transduction and physiology. Cytokine Growth Factor. Rev. 26, 545–558 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a phase III study with 375 patients, another novel NK1R antagonist tradipitant (VLY-686) (EPIONE study), missed the primary end point of reduction in pruritus.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Supportedcites [206] Welsh, S. E. et al. Neurokinin-1 receptor antagonist tradipitant has mixed effects on itch in atopic dermatitis: results from EPIONE, a randomized clinical trial. J. Eur. Acad. Dermatol. Venereol. 35, e338–e340 (2021). source
The EPIONE trial report states that it was a phase 3 trial with 375 patients and that it did not meet its primary endpoint of reducing pruritus. The introduction identifies tradipitant (VLY-686) as an NK-1 receptor antagonist. (LLM, conf=0.95)
plainn = 375- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“After successful phase III studies224,225, topical delgocitinib ointment was approved in 2020 for moderate to severe AD in Japan226.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [224] Nakagawa, H. et al. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J. Am. Acad. Dermatol. 82, 823–831 (2020). source
- Could not verifycites [225] Nakagawa, H. et al. Long-term safety and efficacy of delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with atopic dermatitis. J. Dermatol. 47, 114–120 (2020). sourceExperimental — accuracy not yet measured
Citation 226 is attached to the approval claim, not the preceding phase III results. The Introduction and Discussion describe Japanese delgocitinib studies and their efficacy, but our copy does not state that the ointment was approved in 2020 or specify an approved indication; searches for approval and 2020 found no such passage. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites [226] Dhillon, S. Delgocitinib: first approval. Drugs 80, 609–615 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“The other JAK1-selective JAKi abrocitinib showed similar significant results in phase III238 studies.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Supportedcites [238] Simpson, E. L. et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet 396, 255–266 (2020). Report on a pivotal study showing the good results obtained with the JAK1 inhibitor abrocitinib in AD. source
The Discussion (p. 11) identifies this as a phase 3 trial and reports significant improvement with abrocitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis. The Summary (p. 2) reports statistically significant responses on both coprimary efficacy endpoints. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Besides T cell activation, SYK is a crucial signalling molecule for the high-affinity receptor for IgE (FcεRI) expressed on epidermal Langerhans cells and inflammatory dendritic epidermal cells229–231.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Partly supportedcites [229] Bieber, T. et al. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J. Exp. Med. 175, 1285–1290 (1992). sourceExperimental — accuracy not yet measured
The Summary (p. 1285) states that epidermal Langerhans cells express FcεRI, and the results (p. 1286) identify FcεRI-positive epidermal dendritic cells as Langerhans cells. The cited paper does not establish SYK’s signalling role or address inflammatory dendritic epidermal cells. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [230] Jurgens, M., Wollenberg, A., Hanau, D., de la Salle, H. & Bieber, T. Activation of human epidermal Langerhans cells by engagement of the high affinity receptor for IgE, Fc epsilon RI. J. Immunol. 155, 5184–5189 (1995). source
- Not checked — no full text of the sourcecites [231] Klaeschen, A. S. et al. JAK1/2 inhibition impairs the development and function of inflammatory dendritic epidermal cells in atopic dermatitis. J. Allergy Clin. Immunol. 147, 2202–2212.e8 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, reduction of 50% in SCORAD from baseline was noticed in mild forms of AD206.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Partly supportedcites [206] Welsh, S. E. et al. Neurokinin-1 receptor antagonist tradipitant has mixed effects on itch in atopic dermatitis: results from EPIONE, a randomized clinical trial. J. Eur. Acad. Dermatol. Venereol. 35, e338–e340 (2021). sourceExperimental — accuracy not yet measured
The Figure 2 caption reports that a greater proportion of patients with mild atopic dermatitis achieved at least 50% improvement on SCORAD; it does not report a 50% reduction for the mild subgroup overall. The discussion also says there was no significant SCORAD index improvement in the early weeks. Our copy provides no page number for either passage. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“Depending on their dose-dependent selectivity for one or several JAKs, the JAK inhibitors (JAKi) exert a broad immunopharmacological impact because they block the signal transduction pathways of multiple type I (haematopoietic family) and type II (interferon) cytokine receptors17,214.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Supportedcites [17] Schwartz, D. M. et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat. Rev. Drug Discov. 16, 843–862 (2017). Excellent review on the mode of action of JAK inhibitors. source
The Figure 2 explanation says JAK inhibitors prevent intracellular signal transduction and, because JAKs serve multiple cytokines, block a range of cytokine actions. The discussion of first-generation and selective inhibitors says they inhibit different numbers of JAKs and cytokines, while the selectivity discussion notes that specificity depends on the doses assessed. The paper also identifies type I and II cytokine receptors as JAK-dependent. (LLM, conf=0.91)
- Partly supportedcites [214] Spangler, J. B., Moraga, I., Mendoza, J. L. & Garcia, K. C. Insights into cytokine-receptor interactions from cytokine engineering. Annu. Rev. Immunol. 33, 139–167 (2015). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says cytokine–receptor complexes activate associated JAKs, and the type I interferon section identifies JAK1 and TYK2 in interferon-receptor signaling. The paper does not establish the claimed dose-dependent selectivity of JAK inhibitors or their broad blocking effects across type I and type II cytokine receptors. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the pivotal monotherapy studies (JADE-MONO-1 and JADE-MONO-2), the primary end point IGA 0/1 was reached.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Partly supportedcites [238] Simpson, E. L. et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet 396, 255–266 (2020). Report on a pivotal study showing the good results obtained with the JAK1 inhibitor abrocitinib in AD. sourceExperimental — accuracy not yet measured
The Summary (p. 2) identifies IGA 0/1, with at least a two-grade improvement, as a coprimary endpoint of JADE MONO-1 and reports significantly higher response rates with both abrocitinib doses than with placebo. This paper reports JADE MONO-1, not JADE MONO-2, so it does not establish the claimed result for both studies. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
In the paper
“In line with this concept, even a simple product such as petrolatum has been shown to modulate the antimicrobial and epidermal barrier function47.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the epidermal barrier function
What the sources say
- Not checked — no full text of the sourcecites [47] Czarnowicki, T. et al. Petrolatum: barrier repair and antimicrobial responses underlying this “inert” moisturizer. J. Allergy Clin. Immunol. 137, 1091–1102 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The main cellular and soluble components involved in the pathophysiology of AD represent the key targets of current efforts in pharmacological intervention (Fig. 2).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“In a phase IIa randomized controlled trial (RCT) in adults, B244 given as a spray induced a significant improvement of the pruritus.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Not matchedcites AOBiome press release
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“A similar effect on itching was reported in an open-label phase Ib paediatric trial (see the press release from AOBiome in Related links).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Not matchedcites AOBiome press release
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“The latter mechanism is defective in AD250.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Not checked — no full text of the sourcecites [250] Iwamoto, K. et al. Langerhans and inflammatory dendritic epidermal cells in atopic dermatitis are tolerized toward TLR2 activation. Allergy 73, 2205–2213 (2018). The first report that epidermal DCs isolated from AD skin are tolerant to S. aureus-derived signals. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Dupilumab and tralokinumab are examples of targeted biologic therapies that specifically address a distinct immune pathway and its cytokines or receptors16,”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Introduction
What the sources say
- Not checked — no full text of the sourcecites [16] Wu, J. & Guttman-Yassky, E. Efficacy of biologics in atopic dermatitis. Expert Opin. Biol. Ther. 20, 525–538 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In the past two decades, significant progress has been made in our understanding of the complex phenotype and mechanisms that underlie AD18, offering multiple new potential targets for pharmacological intervention19.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Introduction
What the sources say
- Not checked — no full text of the sourcecites [18] Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. & Irvine, A. D. Atopic dermatitis. Nat. Rev. Dis. Prim. 4, 1 (2018). A key review paper on the current understanding of the pathophysiology of AD. source
- Not checked — no full text of the sourcecites [19] Paller, A. S., Kabashima, K. & Bieber, T. Therapeutic pipeline for atopic dermatitis: end of the drought? J. Allergy Clin. Immunol. 140, 633–643 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A low-dose regimen resulted in a mean percentage change of EASI from baseline of 80.1% versus 49.4% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites Kymab press bulletin
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“By contrast, a phase IIa study in patients with AD showed 64.7% of patients reaching the EASI50 end point versus 48.2% in the placebo group67.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not checked — no full text of the sourcecites [67] Simpson, E. L. et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: a randomized phase 2a clinical trial. J. Am. Acad. Dermatol. 80, 1013–1021 (2019). source
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In the paper
“There were no safety signals reported”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
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In the paper
“However, the interpretation of these data is difficult as all patients were allowed to use TCSs.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
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In the paper
“The mean reduction in EASI from baseline was 74% versus 33% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
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In the paper
“After only 4 weeks of therapy, IGA 0/1 was seen in up to 50% of patients receiving CBP-201 versus 13% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
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In the paper
“These data suggest that this compound represents a promising new option for topical therapy of both AD and psoriasis63, another chronic inflammatory skin disorder.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not checked — no full text of the sourcecites [63] Stein Gold, L., Bhatia, N., Tallman, A. M. & Rubenstein, D. S. A phase 2b, randomized clinical trial of tapinarof cream for the treatment of plaque psoriasis: secondary efficacy and patient-reported outcomes. J. Am. Acad. Dermatol. 84, 624–631 (2020). source
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In the paper
“However, in a larger phase IIa study (ATLAS study) with 300 adult patients, the primary end point was not reached (see the press release from AnaptysBio in Related links).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not matchedcites AnaptysBio press release
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 300- Asserted: passes — The authors put it forward as true.
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In the paper
“IL-36 is another player in the innate immune system that is upregulated in the skin of psoriasis as well as AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
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In the paper
“Dupilumab binds to IL-4Rα, the chain common to the type I (IL-4Rα/IL-2Rγ) and type II (IL-4Rα/IL-13Rα1) receptors for IL-4 and IL-13”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites refs81,82
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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In the paper
“Although the mode of action is theoretically similar to that of dupilumab, it seems to have a faster onset of action.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The antibody also improved the gene signatures in the skin78.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [78] Guttman-Yassky, E. et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J. Allergy Clin. Immunol. 144, 482–493 (2019). First report on the therapeutic potential of a targeted therapy aiming to impact antigen presentation. source
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In the paper
“It exerts pro- and anti-inflammatory activities, depending on the cell type, the micromilieu and the ligand, that is, exogenous and endogenous metabolites and agents58.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not checked — no full text of the sourcecites [58] Trikha, P. & Lee, D. A. The role of AhR in transcriptional regulation of immune cell development and function. Biochim. Biophys. Acta Rev. Cancer 1873, 188335 (2020). source
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In the paper
“The underlying ‘march of the adaptive immune system’ starts from antigen presentation and affects varrious pathways, ultimately offering distinct therapeutic options18,19,75–77.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [18] Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. & Irvine, A. D. Atopic dermatitis. Nat. Rev. Dis. Prim. 4, 1 (2018). A key review paper on the current understanding of the pathophysiology of AD. source
- Not checked — no full text of the sourcecites [19] Paller, A. S., Kabashima, K. & Bieber, T. Therapeutic pipeline for atopic dermatitis: end of the drought? J. Allergy Clin. Immunol. 140, 633–643 (2017). source
- Not checked — no full text of the sourcecites [75] Brunner, P. M. Early immunologic changes during the onset of atopic dermatitis. Ann. Allergy Asthma Immunol. 123, 152–157 (2019). source
- Not checked — no full text of the sourcecites [76] Brunner, P. M. et al. The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult, longstanding disease. J. Am. Acad. Dermatol. 81, 510–519 (2019). source
- Not checked — no full text of the sourcecites [77] Zhou, L. et al. Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis. J. Allergy Clin. Immunol. 144, 144–156 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The heterogeneity of the clinical phenotype of AD most probably reflects the highly complex pathophysiology.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“As it is expressed in keratinocytes and resident epidermal dendritic cells (DCs), AhR represents an ideal target for a topical pharmacological approach.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
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In the paper
“IGA 0/1 was reached in 44% of those who received KY1005 versus 8% in the placebo group”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites Kymab press bulletin
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The aryl-hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor with a Janus-faced role in physiology and the pathophysiology of several skin disorders including AD56,57.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not checked — no full text of the sourcecites [56] Haarmann-Stemmann, T., Esser, C. & Krutmann, J. The Janus-faced role of aryl hydrocarbon receptor signaling in the skin: consequences for prevention and treatment of skin disorders. J. Invest. Dermatol. 135, 2572–2576 (2015). source
- Not checked — no full text of the sourcecites [57] Hidaka, T. et al. The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin. Nat. Immunol. 18, 64–73 (2017). Important paper reporting on the role of the xenobiotic receptor AhR in sensing environmental factors to induce AD lesions in an animal model. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As, for regulatory reasons, proof-of-concept studies are primarily performed in adults, the limited efficacy observed in some studies such as those targeting TSLP or IL-33 may not predict their efficacy in an early phase of the disease, that is, in the paediatric population.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Given their key role in initiation of the skin-derived immune response, alarmins are interesting therapeutic targets.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, EASI75 was reached in 25% and 33% of patients receiving treatment in the two trials versus 13% and 11% receiving placebo, respectively.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
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In the paper
“using weight-adapted doses of omalizumab in children with high total serum IgE, there was a significant difference in the change from baseline for the objective SCORAD as primary end point compared with the placebo group114.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [114] Chan, S., Cornelius, V., Cro, S., Harper, J. I. & Lack, G. Treatment effect of omalizumab on severe pediatric atopic dermatitis: the ADAPT randomized clinical trial. JAMA Pediatr. 174, 29–37 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“strategies aimed at depleting IgE with the anti-IgE biologic omalizumab failed to show convincing results in proof-of-concept studies and single cases107,108.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [107] Heil, P. M., Maurer, D., Klein, B., Hultsch, T. & Stingl, G. Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course - a randomized, placebo-controlled and double blind pilot study. J. Dtsch. Dermatol. Ges. 8, 990–998 (2010). source
- Not checked — no full text of the sourcecites [108] Krathen, R. A. & Hsu, S. Failure of omalizumab for treatment of severe adult atopic dermatitis. J. Am. Acad. Dermatol. 53, 338–340 (2005). source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This suggests that tralokinumab develops its full potential at a later time point.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The mean rate of eye disorders for both ECZTRA1 and ECZTRA2 studies with tralokinumab at week 16 was 7.6% versus 3% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Similar results were obtained for the EASI score.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Lebrikizumab is another fully humanized anti-IL-13 antibody that does not block the binding of the cytokine to the receptor but instead impairs the heterodimerization of IL-4Rα and IL-13Rα1, thereby inhibiting signal transduction91,95.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [91] May, R. D. & Fung, M. Strategies targeting the IL-4/IL-13 axes in disease. Cytokine 75, 89–116 (2015). source
- Not checked — no full text of the sourcecites [95] Ultsch, M. et al. Structural basis of signaling blockade by anti-IL-13 antibody lebrikizumab. J. Mol. Biol. 425, 1330–1339 (2013). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These observations imply a role for IgE-bearing antigen-presenting epidermal DCs such as Langerhans cells in the capture and presentation of allergens to T cells106.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [106] Novak, N. et al. FcεRI engagement of Langerhans cell-like dendritic cells and inflammatory dendritic epidermal cell-like dendritic cells induces chemotactic signals and different T-cell phenotypes in vitro. J. Allergy Clin. Immunol. 113, 949–957 (2004). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“This cytokine is induced by staphylococcal exotoxins118 in numerous inflammatory cells, including TH1 and TH17 cells.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [118] Niebuhr, M., Scharonow, H., Gathmann, M., Mamerow, D. & Werfel, T. Staphylococcal exotoxins are strong inducers of IL-22: a potential role in atopic dermatitis. J. Allergy Clin. Immunol. 126, 1176–1183 (2010). source
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The efficacy was mirrored by a rapid improvement in the pruritus NRS.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This approach would lead to long-term reduction in IgE-mediated reactions in allergic individuals, including patients with AD115.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [115] Liour, S. S., Tom, A., Chan, Y. H. & Chang, T. W. Treating IgE-mediated diseases via targeting IgE-expressing B cells using an anti-CεmX antibody. Pediatr. Allergy Immunol. 27, 446–451 (2016). Explains the strategy of depleting IgE-committed B cells by targeting membrane IgE. source
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“provocation tests with food allergens as well as with aeroallergens induce exacerbation in a subgroup of AD patients104,105.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [104] Werfel, T. et al. Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber. J. Allergy Clin. Immunol. 136, 96–103 (2015). Further evidence for a role of IgE-mediated allergy to aeroallergens in AD. source
- Not checked — no full text of the sourcecites [105] Roerdink, E. M. et al. Association of food allergy and atopic dermatitis exacerbations. Ann. Allergy Asthma Immunol. 116, 334–338 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Antigen-specific TH2 cells represent a numerically important component of the dermal and epidermal infiltrates in AD18.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [18] Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. & Irvine, A. D. Atopic dermatitis. Nat. Rev. Dis. Prim. 4, 1 (2018). A key review paper on the current understanding of the pathophysiology of AD. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Difamilast (OPA-15406/MM36) administered as a cream has been shown to be effective in adolescents and adults in a phase IIa study134.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [134] Hanifin, J. M. et al. OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): a phase-II randomized, double-blind, placebo-controlled study. J. Am. Acad. Dermatol. 75, 297–305 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“By the production of a large variety of mediators, T cells contribute to the generation of a dynamic and disease-specific inflammatory micromilieu with a strong impact on epidermal barrier function.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These promising results were confirmed in two phase III pivotal trials completed in Japan (see the press release in Related links).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites press release
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Not matched
In the paper
“In these animal models, the activity was similar to that of an anti-IL-13 antibody”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites Rapt Therapeutics Form 8-K
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“CRTH2 is preferentially expressed on TH2 cells152,153”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [152] Cosmi, L. et al. CRTH2 is the most reliable marker for the detection of circulating human type 2Th and type 2 T cytotoxic cells in health and disease. Eur. J. Immunol. 30, 2972–2979 (2000). source
- Not checked — no full text of the sourcecites [153] Iwasaki, M. et al. Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis. J. Invest. Dermatol. 119, 609–616 (2002). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Promising results have been obtained initially with lotamilast (RVT-501/E6005) in a cream in Japanese adults and children132,133.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [132] Furue, M. et al. Safety and efficacy of topical E6005, a phosphodiesterase 4 inhibitor, in Japanese adult patients with atopic dermatitis: results of a randomized, vehicle-controlled, multicenter clinical trial. J. Dermatol. 41, 577–585 (2014). source
- Not checked — no full text of the sourcecites [133] Nemoto, O. et al. Effect of topical phosphodiesterase 4 inhibitor E6005 on Japanese children with atopic dermatitis: results from a randomized, vehicle-controlled exploratory trial. J. Dermatol. 43, 881–887 (2016). source
plainconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“both CRTH2 antagonists fevipiprant (QAW039) and temapiprant (OC000459) failed to significantly improve AD in phase II studies.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In preclinical experiments, RPT193, a small-molecule CCR4 antagonist, selectively blocks the recruitment of TH2 cells in allergic diseases.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites Rapt Therapeutics Form 8-K
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An alternative approach is the topical administration of PDE4 inhibitors, thereby avoiding the typical gastrointestinal adverse events observed with systemic application.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“First reports from a phase I study showed no serious adverse events in 64 healthy subjects after single and multiple dosing”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites RAPT Therapeutics press release
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 64- Asserted: passes — The authors put it forward as true.
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- Not matched
In the paper
“Prostaglandin D2 and its receptor (PGDR2/CRTH2) play an important role in the generation of inflammation151.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [151] Marone, G. et al. Prostaglandin D2 receptor antagonists in allergic disorders: safety, efficacy, and future perspectives. Expert Opin. Investig. Drugs 28, 73–84 (2019). Interesting review on the pharmacology of PGD2 receptor antagonists. source
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Etrasimod was overall well tolerated”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In a phase IIa study, the anti-IL-31Rα antibody nemolizumab led to a significant decrease in the pruritus sensation”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [189] Ruzicka, T. et al. Anti-interleukin-31 receptor a antibody for atopic dermatitis. N. Engl. J. Med. 376, 826–835 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the phase IIb ADVISE trial, etrasimod achieved the primary end point validated IGA (vIGA) 0/1 in 36.8% versus 13% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites press statement
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the concomitant use of TCSs and the lack of placebo arm in this extension study makes the interpretation challenging.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the drug did not induce adverse events such as cardiovascular toxicity commonly seen with this class of compound.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Of note, nemolizumab generated promising results in prurigo nodularis, a highly pruritic skin disorder assumed to be related to AD193.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [193] Stander, S. et al. Trial of nemolizumab in moderate-to-severe prurigo nodularis. N. Engl. J. Med. 382, 706–716 (2020). Report on the efficacy of the anti-IL-31 biologic nemolizumab in prurigo nodularis. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- The authors state this as an assumption: Prurigo nodularis is related to atopic dermatitis.
In the paper
“while achieving clinical improvement in a dose-independent fashion190.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [190] Kabashima, K. et al. Nemolizumab in patients with moderate-to-severe atopic dermatitis: randomized, phase II, long-term extension study. J. Allergy Clin. Immunol. 142, 1121–1130 (2018). source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In the 52-week long-term extension of this study, the efficacy towards itching was confirmed”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [190] Kabashima, K. et al. Nemolizumab in patients with moderate-to-severe atopic dermatitis: randomized, phase II, long-term extension study. J. Allergy Clin. Immunol. 142, 1121–1130 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In another phase II study, the expected early improvement in itching was captured by the decrease in PP-NRS (69% versus 34%).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [191] Silverberg, J. I. et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J. Allergy Clin. Immunol. 145, 173–182 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“but the overall clinical inflammation as evaluated by the body surface area (BSA), EASI and IGA scorings did not improve significantly at this time point189.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [189] Ruzicka, T. et al. Anti-interleukin-31 receptor a antibody for atopic dermatitis. N. Engl. J. Med. 376, 826–835 (2017). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Targeting IL-31 and its receptor is a focus of strategies to better control itching188.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [188] Nakashima, C., Otsuka, A. & Kabashima, K. Interleukin-31 and interleukin-31 receptor: new therapeutic targets for atopic dermatitis. Exp. Dermatol. 27, 327–331 (2018). source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The overall efficacy in pruritus in combination with TCSs was further confirmed in a phase III study over 16 weeks with a decrease of 43% versus 21% in the placebo group as measured by the visual analogue scale score.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [192] Kabashima, K., Matsumura, T., Komazaki, H. & Kawashima, M., Nemolizumab-JP01 Study Group. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N. Engl. J. Med. 383, 141–150 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The topical application of the prototypical S1PR agonist fingolimod (mol. wt 343) has been reported to reduce allergic inflammation in animal models of skin disorders169–171.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [169] Tsuji, T. et al. Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice. Allergol. Int. 65, 172–179 (2016). source
- Not checked — no full text of the sourcecites [170] Schaper, K. et al. Sphingosine-1-phosphate exhibits anti-proliferative and anti-inflammatory effects in mouse models of psoriasis. J. Dermatol. Sci. 71, 29–36 (2013). source
- Not checked — no full text of the sourcecites [171] Park, S. J. & Im, D. S. Blockage of sphingosine-1-phosphate receptor 2 attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice. Acta Pharmacol. Sin. 41, 1487–1496 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The EASI score showed a moderate improvement of 46% with nemolizumab versus 33% in the placebo group192.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [192] Kabashima, K., Matsumura, T., Komazaki, H. & Kawashima, M., Nemolizumab-JP01 Study Group. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N. Engl. J. Med. 383, 141–150 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“IGA 0/1 was reached in 33% of the patients versus 12% in the placebo group at week 16”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [191] Silverberg, J. I. et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J. Allergy Clin. Immunol. 145, 173–182 (2020). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, there was no significant effect on EASI and SCORAD194.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [194] Mihak, Z. et al. KPL-716, anti-Oncostatin M receptor beta antibody, reduced pruritus in atopic dermatitis [abstract 560]. J. Invest. Dermatol. 139 (Suppl.), S96 (2019). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Currently available data suggest that in AD, itching is a result of inflammation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In this population, the primary end point IGA 0/1 was reached in 17% versus 5% for placebo (BREEZE-AD1 study)”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [235] Simpson, E. L. et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomised monotherapy phase 3 trials. Br. J. Dermatol. 183, 242–255 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“However, in another large phase II study (ATOMIK study; 484 participants) and in patients with AD, the drug missed the primary end point of change in worst itch NRS from baseline (NCT02975206).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not matchedcites NCT02975206
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 484- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“However, this conclusion may not be generalized for a number of itchy skin disorders such as prurigo nodularis in which targeting itch remains promising193,205,210–212.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [193] Stander, S. et al. Trial of nemolizumab in moderate-to-severe prurigo nodularis. N. Engl. J. Med. 382, 706–716 (2020). Report on the efficacy of the anti-IL-31 biologic nemolizumab in prurigo nodularis. source
- Not checked — no full text of the sourcecites [205] Stander, S. et al. Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial. J. Am. Acad. Dermatol. 80, 1395–1402 (2019). source
- Not checked — no full text of the sourcecites [210] Stander, S., Spellman, M. C., Kwon, P. & Yosipovitch, G. The NK1 receptor antagonist serlopitant for treatment of chronic pruritus. Expert Opin. Investig. Drugs 28, 659–666 (2019). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“In a pooled safety analysis of the cumulative data from eight studies with 2,531 patients (2,247 patient-years with median duration of 310 days) there were no signals for serious or opportunistic infections236.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [236] Bieber, T. et al. Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J. Eur. Acad. Dermatol. Venereol. 35, 476–485 (2020). source
plainn = 2,531- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Serlopitant is a NK1R antagonist that has shown efficacy in reducing pruritus in a phase II study in patients with treatment-refractory prurigo nodularis205.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [205] Stander, S. et al. Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial. J. Am. Acad. Dermatol. 80, 1395–1402 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As a common feature of all JAKi, there was a rapid (within 36 h) and sustained reduction in the itch sensation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As the receptors for TH2 and TH22 cytokines involve downstream JAK–STAT signalling, JAKi represent interesting compounds for the therapy of AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“suggesting that this signalling pathway could be pharmacologically targeted to control itching sensation and neurogenic inflammation203,204.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [203] Stander, S. & Luger, T. A. NK-1 antagonists and itch. Handb. Exp. Pharmacol. 226, 237–255 (2015). source
- Not checked — no full text of the sourcecites [204] Zeidler, C. & Stander, S. The pathogenesis of prurigo nodularis–‘super-itch’ in exploration. Eur. J. Pain. 20, 37–40 (2016). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, simultaneous targeting of JAKs and SYK by cerdulatinib appears to be an appealing strategy for topical pharmacological intervention in AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Overexpression of substance P and NK1R induces itching skin disorders including AD199–202”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [199] Pincelli, C. et al. Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study. Br. J. Dermatol. 122, 745–750 (1990). source
- Not checked — no full text of the sourcecites [200] Tobin, D. et al. Increased number of immunoreactive nerve fibers in atopic dermatitis. J. Allergy Clin. Immunol. 90, 613–622 (1992). source
- Not checked — no full text of the sourcecites [201] Jarvikallio, A., Harvima, I. T. & Naukkarinen, A. Mast cells, nerves and neuropeptides in atopic dermatitis and nummular eczema. Arch. Dermatol. Res. 295, 2–7 (2003). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Interestingly, unlike selective JAKi (see below), there was no increase in acne under baricitinib.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [236] Bieber, T. et al. Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J. Eur. Acad. Dermatol. Venereol. 35, 476–485 (2020). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and 14% versus 5% in the placebo group (BREEZE-AD2 study)235.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [235] Simpson, E. L. et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomised monotherapy phase 3 trials. Br. J. Dermatol. 183, 242–255 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Translational efforts to convert this knowledge into drug discovery have paved the way for an impressive number of preclinical and clinical development programmes.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“There are multiple factors that contribute to the high heterogeneity of the age of disease onset in patients with AD, the variations in the clinical phenotype (particularly in different ethnic backgrounds) and the different risks for early development of an ‘atopic march’ with atopic comorbidities (that is, allergic rhinitis and asthma), neuropsychiatric comorbidities (anxiety, depression) or”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These factors, which include diverse environmental influences, a complex genotype, microbiome-derived signals and a dynamic immune response, also underlie the highly variable therapeutic response and adverse events to established and new compounds for AD therapy243.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
What the sources say
- Not checked — no full text of the sourcecites [243] Agnihotri, G. & Lio, P. A. Revisiting therapies for atopic dermatitis that failed clinical trials. Clin. Drug Investig. 40, 421–431 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clearly, as for rheumatoid arthritis, JAKi are not the ‘one-size-fits-all’ approach for AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, although patients expect that such new compounds provide full clinical response in a monotherapy regimen, the phase III trials with these compounds have highlighted the variability of the clinical response.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is certainly the case for the JAK1/JAK2 inhibitor baricitinib, for which the identification of the good-responder population is an unmet need.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“In an animal model of AD, HY209 reduced TH2 inflammation via inhibition of nuclear factor κB (NF-κB) and p38 kinase.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not checked — no full text of the sourcecites [240] Ghaderpour, A., Kim, Y.-H., Lee, H.-C. & Seong, S.-Y. HY209 ameliorates atopic dermatitis through NF-KB and P38 inhibition. J. Immunol. 204 (Suppl. 1), 147.37 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the phase III data of the dual JAK1/JAK2 inhibitor baricitinib suggest a lower efficacy than the more JAK1-specific inhibitors abrocitinib and upadacitinib.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“An early precise determination of the genetic and/or environmental risk factors leading to the emergence of AD in infancy as well as the risk of developing an atopic march (that is, atopic comorbidities such as allergic asthma) bears the tremendous potential of a disease-modifying prevention strategy early in life244.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
What the sources say
- Not checked — no full text of the sourcecites [244] Bieber, T., Cork, M. & Reitamo, S. Atopic dermatitis: a candidate for disease-modifying strategy. Allergy 67, 969–975 (2012). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“However, the compound did not significantly downregulate markers of inflammation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not matchedcites NCT02655679
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consequently, there is now an expanding pipeline for the therapy of this complex disorder.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Another approach to affect inflammation is to inhibit the tropomyosin receptor kinases (TRKs), which bind neurotrophins known to aggravate skin inflammation239.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not checked — no full text of the sourcecites [239] Peters, E. M. et al. Nerve growth factor partially recovers inflamed skin from stress-induced worsening in allergic inflammation. J. Invest. Dermatol. 131, 735–743 (2011). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Moreover, the effects observed were not dose-dependent (NCT02655679).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not matchedcites NCT02655679
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The steadily increasing number of new drugs in development for AD has indicated the potential for precision medicine to generate an optimized benefit–risk ratio, particularly in age ranges where safety issues are of crucial interest such as in paediatric patients, as well as in the elderly, where drug–drug interactions represent another potential threat.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 98
- Probably not a substantial claim. 39
- The quote only partly states this claim. 2
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The skin microbiome is regulated on one hand by the quorum-sensing mechanisms between bacterial strains26 and on the other hand by the crosstalk between the bacteria and the skin innate immune system and epidermal Langerhans cells continuously educating the adaptive immune system.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Supportedcites [26] Williams, M. R. et al. Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis. Sci. Transl Med. 11, eaat8329 (2019). source
Citation 26 is attached to the quorum-sensing clause, not the subsequent claim about immune-system crosstalk. The Introduction and Discussion report that autoinducing peptides from some skin commensal staphylococcal strains repress S. aureus quorum-sensing activity, demonstrating regulation between bacterial strains on the skin. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [250] Iwamoto, K. et al. Langerhans and inflammatory dendritic epidermal cells in atopic dermatitis are tolerized toward TLR2 activation. Allergy 73, 2205–2213 (2018). The first report that epidermal DCs isolated from AD skin are tolerant to S. aureus-derived signals. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Skin from patients with AD presents significant differences in the microbiome compared with healthy individuals, in whom Roseomonas mucosa was found to be the most representative Gram-negative bacteria41.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Partly supportedcites [41] Paller, A. S. et al. The microbiome in patients with atopic dermatitis. J. Allergy Clin. Immunol. 143, 26–35 (2019). sourceExperimental — accuracy not yet measured
The “AD AND S AUREUS: EPIDEMIOLOGY” section reports reduced microbial diversity during AD flares and greater S aureus carriage than in healthy controls, supporting a difference in skin microbiomes. The “CAN COMMENSAL ORGANISMS BE USED AS THERAPY FOR AD?” section identifies Roseomonas mucosa as Gram-negative, but does not say it is the most representative Gram-negative bacterium in healthy individuals. Page numbers were not available in our copy. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“T helper 2 (TH2) immune polarization is accompanied by IgE sensitization to environmental allergens and self proteins and has a key role in atopic disorders101,257.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Partly supportedcites [101] Tang, T. S., Bieber, T. & Williams, H. C. Does “autoreactivity” play a role in atopic dermatitis? J. Allergy Clin. Immunol. 129, 1209–1215 (2012). Review paper analysing the evidence for autoimmunity in AD. sourceExperimental — accuracy not yet measured
The Figure 3 caption (Clinical and research implications; page unavailable) describes a proposed mechanism in atopic dermatitis in which a TH2 response accompanies IgE directed against self-proteins. The paper also discusses IgE responses to environmental allergens, but its Abstract says the role of autoreactivity is unclear and reports no IgE autoreactivity in subjects with allergic rhinoconjunctivitis. It therefore does not establish the claimed key role of this combined sensitization across atopic disorders. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [257] Valenta, R. et al. Immunoglobulin E response to human proteins in atopic patients. J. Invest. Dermatol. 107, 203–208 (1996). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“After initial promising results using such emollients and moisturizers in the prevention of AD in newborns at high risk48,49, a more recent report has questioned this strategy50,51.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the epidermal barrier function
What the sources say
- Supportedcites [48] Simpson, E. L. et al. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J. Allergy Clin. Immunol. 134, 818–823 (2014). source
The Methods describe a trial of emollient use from birth in neonates at high risk of atopic dermatitis. The Results report a lower incidence at six months in the emollient group (22% versus 43% in controls), supporting the cited description of initial promising results. The later report questioning the strategy is attributed to citations 50 and 51, not this source. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [49] Horimukai, K. et al. Application of moisturizer to neonates prevents development of atopic dermatitis. J. Allergy Clin. Immunol. 134, 824–830 (2014). Together with Simpson et al. (2014), first reported on the putative preventive value of simple skin care in newborns at risk of developing AD. source
- Supportedcites [50] Perrett, K. P. & Peters, R. L. Emollients for prevention of atopic dermatitis in infancy. Lancet 395, 923–924 (2020). source
The paper describes promising signals from small pilot studies (p. 1), then reports that a larger trial in high-risk newborns found no preventive effect (p. 1). It concludes that emollients should not currently be recommended for primary prevention of atopic dermatitis in infants (p. 2), directly supporting the claim that a more recent report questioned the strategy. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [51] Skjerven, H. O. et al. Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial. Lancet 395, 951–961 (2020). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The role of the innate immune system in the early phase of AD was demonstrated using animal models52–54 and is likely of clinical relevance in infancy55.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Supportedcites [52] Briot, A. et al. Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J. Exp. Med. 206, 1135–1147 (2009). source
Citation 55 is attached to the claim of likely clinical relevance in infancy. The Discussion says the epithelial mechanism identified in this study could explain why eczematous lesions in infants often begin before specific IgE antibodies appear. That supports the citing sentence’s hedged claim; the animal-model clause is attributed to citations 52–54. (LLM, conf=0.88)
- Partly supportedcites [53] Saunders, S. P. et al. Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity. J. Allergy Clin. Immunol. 137, 482–491 (2016). sourceExperimental — accuracy not yet measured
The Results section on cutaneous inflammation shows that filaggrin-deficient mice develop dermatitis without adaptive immunity, and the Discussion reports increased skin ILC2s in patients with atopic dermatitis and filaggrin mutations. The paper also describes atopic dermatitis as an early-life condition, but it does not establish that the innate-immune finding applies specifically to infants; clinical relevance in infancy remains an extrapolation. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [54] Chieosilapatham, P. et al. Keratinocytes: innate immune cells in atopic dermatitis. Clin. Exp. Immunol. 204, 296–309 (2021). source
- Partly supportedcites [55] Han, H., Roan, F. & Ziegler, S. F. The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines. Immunol. Rev. 278, 116–130 (2017). sourceExperimental — accuracy not yet measured
The Introduction says atopic dermatitis often begins in infancy, and section 6.1 reports an epithelial-derived cytokine in human atopic-dermatitis lesions and its role in mouse models of skin inflammation. These passages make clinical relevance in infancy plausible, but the copy does not establish the role of innate immunity specifically in the early phase of infant atopic dermatitis. The animal-model demonstration is attached to other citations in the citing sentence. (LLM, conf=0.79)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The itch-scratching reflex contributes to further disruption of the epidermal barrier function, keratinocyte damage and activation of local dendritic cells, which in turn will further activate the adaptive immune response and subsequent inflammatory reaction29,181,182.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Not checked — no full text of the sourcecites [29] Mack, M. R. & Kim, B. S. The itch-scratch cycle: a neuroimmune perspective. Trends Immunol. 39, 980–991 (2018). source
- Not checked — no full text of the sourcecites [181] Erickson, S., Heul, A. V. & Kim, B. S. New and emerging treatments for inflammatory itch. Ann. Allergy Asthma Immunol. 126, 13–20 (2021). source
- Partly supportedcites [182] Yang, T. B. & Kim, B. S. Pruritus in allergy and immunology. J. Allergy Clin. Immunol. 144, 353–360 (2019). sourceExperimental — accuracy not yet measured
The Prurigo Nodularis section (page not available) says itch is believed to drive rash development and describes chronic scratching, supporting a general link between itch and skin lesions. The Atopic Dermatitis section discusses barrier-derived cytokines and immune inflammation, but the copy does not establish that scratching damages keratinocytes or activates dendritic cells, which then amplify the adaptive immune response. (LLM, conf=0.74)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“So far, however, AD has primarily been considered as merely a skin disorder in which local anti-inflammatory therapy of the disease flares should be the first-line approach14,15.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Introduction
What the sources say
- Could not verifycites [14] Vestergaard, C., Wollenberg, A. & Thyssen, J. P. European Task Force on Atopic Dermatitis (ETFAD) Position Paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period. J. Eur. Acad. Dermatol. Venereol. 34, 426–427 (2020). sourceExperimental — accuracy not yet measured
The available passage, under “Crisaborole ointment is not recommended for treatment of AD in pregnant women” (page unavailable), discusses medication safety during pregnancy and lactation. Searches for local anti-inflammatory treatment of flares and first-line topical therapy found no passage addressing whether AD has primarily been regarded as a skin disorder or whether such therapy should be first-line. (LLM, conf=0.73)
- Not checked — no full text of the sourcecites [15] Thyssen, J. P. et al. European Task Force on Atopic Dermatitis (ETFAD): treatment targets and treatable traits in atopic dermatitis. J. Eur. Acad. Dermatol. Venereol. 34, e839–e842 (2020). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The Harmonising Outcome Measures for Eczema (HOME) initiative has established a core outcome set of tools and end points to be used in clinical trials258–261 and are discussed in detail elsewhere37.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Partly supportedcites [258] Schmitt, J. et al. The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials. J. Allergy Clin. Immunol. 134, 800–807 (2014). sourceExperimental — accuracy not yet measured
Step 2 identifies four core outcome domains for atopic eczema trials, and Step 3 reports that HOME selected EASI to measure clinical signs. But Step 3 says instruments for the other domains had not yet been agreed on, so the paper does not support the claim that a full set of tools had been established. Page numbers are unavailable in our copy. (LLM, conf=0.90)
- Partly supportedcites [259] Chalmers, J. R. et al. Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative). Br. J. Dermatol. 175, 69–79 (2016). sourceExperimental — accuracy not yet measured
The paper identifies four core outcome domains for atopic eczema trials and reports recommended instruments for clinician-reported signs and patient-reported symptoms (DOI section). But it says preferred instruments for quality of life and long-term control still require further work, so it does not support the implication that a complete set of tools had been established. (LLM, conf=0.88)
- Partly supportedcites [260] Langan, S. M. et al. Measuring long-term disease control in patients with atopic dermatitis: a validation study of well-controlled weeks. J. Allergy Clin. Immunol. 140, 1580–1586 (2017). sourceExperimental — accuracy not yet measured
The References section cites HOME consensus work on core outcome measures for atopic dermatitis trials, supporting HOME’s role in harmonising trial outcomes. But the Clinical and research implications section says that how to measure long-term control remained a HOME research priority, and the paper does not say that a complete core set of tools and end points had been established. Page numbers are not available in our copy. (LLM, conf=0.83)
- Supportedcites [261] Thomas, K. S. et al. Recommended core outcome instruments for health-related quality of life, long-term control and itch intensity in atopic eczema trials: results of the HOME VII consensus meeting. Br. J. Dermatol. https://doi.org/10.1111/bjd.19673 (2021). source
The paper’s clinical implications section identifies four HOME core domains for atopic eczema trials and names recommended instruments for signs and symptoms. Its conclusion states that the core outcome set is complete and that the specified domains and instruments should be used in new clinical trials. Page numbers are unavailable in our copy. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Therefore, individually and empirically adapted skin care using emollients or moisturizers to complement the control of inflammation still remains the only approach to improve barrier function, dryness and water loss and is qualified as basis therapy35.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the epidermal barrier function
What the sources say
- Partly supportedcites [35] Wollenberg, A. et al. ETFAD/EADV Eczema Task Force 2020 Position Paper on diagnosis and treatment of atopic dermatitis in adults and children. J. Eur. Acad. Dermatol. Venereol. 34, 2717–2744 (2020). sourceExperimental — accuracy not yet measured
The Emollient therapy section (p. 7) recommends daily emollients and explains that their ingredients hydrate the skin and reduce evaporation; it also advises treating acute inflammation with anti-inflammatory topicals first. The paper places skincare under basic therapy (p. 5), but does not say that individually adapted emollient care is the only approach to improving barrier function, dryness, and water loss. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Tapinarof (also known as benvitimod) is a natural AhR agonist60 that significantly reduces inflammatory responses both in animal models and in human skin when used topically.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Supportedcites [60] Smith, S. H. et al. Tapinarof Is a natural AhR agonist that resolves skin inflammation in mice and humans. J. Invest. Dermatol. 137, 2110–2119 (2017). source
The opening summary (p. 1) identifies tapinarof as a naturally derived topical treatment and AhR agonist. It reports reduced inflammatory measures after topical treatment in mice and moderated proinflammatory cytokine expression in ex vivo human skin; the Th17 cytokine section (p. 5) reports approximately 50% inhibition of IL17A expression in a human-skin model. (LLM, conf=0.91)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“IL-1α is a proinflammatory cytokine released by keratinocytes after injury and by skin dysbiosis69.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Supportedcites [69] Archer, N. K. et al. Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1alpha release. J. Allergy Clin. Immunol. 143, 1426–1443 (2019). source
The Discussion states that keratinocytes release intracellular IL-1α following skin injury and dysbiosis, and that the released IL-1α drives skin inflammation. The Results also report increased IL-1α release from mechanically injured keratinocytes. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“It is approved for AD in many countries and real-world data support the efficacy reported in the phase III programme in adults83–86.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [83] Faiz, S. et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. J. Am. Acad. Dermatol. 81, 143–151 (2019). sourceExperimental — accuracy not yet measured
The Discussion reports that this real-life adult AD study found effectiveness similar to that observed in clinical trials, supporting the efficacy comparison. The Introduction calls dupilumab available for adult AD, but the cited passages do not establish approval in many countries. (LLM, conf=0.85)
- Partly supportedcites [84] Abraham, S. et al. Implementation of dupilumab in routine care of atopic eczema. Results from the German national registry TREATgermany. Br. J. Dermatol. 183, 382–384 (2020). sourceExperimental — accuracy not yet measured
The Abstract reports real-world results in adults with atopic eczema and concludes that they show no major efficacy–effectiveness gap, largely confirming trial data. It says dupilumab was launched in Germany, but does not establish approval for AD in many countries. (LLM, conf=0.87)
- Partly supportedcites [85] Deleuran, M. et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. J. Am. Acad. Dermatol. 82, 377–388 (2020). sourceExperimental — accuracy not yet measured
The introductory passage (page unavailable) reports dupilumab approvals for AD in the United States, Japan, and Europe and describes efficacy in phase 1–3 trials. The Methods and Discussion (pages unavailable) identify this paper as a clinical-trial open-label extension, not real-world data; it therefore does not support the real-world-data part of the claim. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [86] Wang, C., Kraus, C. N., Patel, K. G., Ganesan, A. K. & Grando, S. A. Real-world experience of dupilumab treatment for atopic dermatitis in adults: a retrospective analysis of patients’ records. Int. J. Dermatol. 59, 253–256 (2020). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Therefore, the anti-IL-36R antibody spesolimab, which has been successfully tested in a rare form of pustular psoriasis74, has been explored for AD in a phase IIa study with 51 patients, the results of which are expected by the end of 2021.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Supportedcites [74] Bachelez, H. et al. Inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. N. Engl. J. Med. 380, 981–983 (2019). source
The citation is attached to the claim that the anti-IL-36-receptor antibody was tested in a rare form of pustular psoriasis, not to the later statement about the atopic-dermatitis study. The opening passage (p. 1) describes a seven-patient proof-of-concept study in generalized pustular psoriasis, and the results (p. 1) report clear or almost clear skin in all seven by week 4. The authors caution that further investigation is needed to establish clinical efficacy (p. 3). (LLM, conf=0.91)
plainn = 51- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In a proof-of-concept study with a single application of the anti-IL-33 antibody etokimab (ANB020) in 12 patients with moderate or severe AD, 33% of patients reached the primary end point EASI75 and 83% reached EASI50 (ref.68).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Partly supportedcites [68] Chen, Y. L. et al. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci. Transl Med. 11, eaax2945 (2019). sourceExperimental — accuracy not yet measured
The Study design section describes a single dose of etokimab in 12 adults with moderate-to-severe atopic dermatitis, and Efficacy reports 33% reaching EASI75 and 83.3% reaching EASI50 at day 29. The citing sentence also calls EASI75 the primary endpoint, but Study design lists EASI scores among the main clinical endpoints and does not identify EASI75 as the primary endpoint. Page numbers were not available in our copy. (LLM, conf=0.86)
plaindirectn = 12- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the pivotal studies with dupilumab, 11% of the patients developed eye disorders (for example, conjunctivitis, keratoconjunctivitis and keratitis); this adverse event of special interest (AESI) has been attributed to its IL-13 blocking activity93.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [93] Akinlade, B. et al. Conjunctivitis in dupilumab clinical trials. Br. J. Dermatol. 181, 459–473 (2019). sourceExperimental — accuracy not yet measured
The Incidence of conjunctivitis section reports increased conjunctivitis in dupilumab-treated patients with atopic dermatitis, but rates varied by trial (8.6%, 17.9%, and 22.1%); it does not report 11% of dupilumab patients developing eye disorders. The Discussion (page unavailable in our copy) lists reduced IL-13-related mucus production among several proposed mechanisms and says the exact pathogenesis is unknown, so it does not establish IL-13 blockade as the cause. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Higher rates were described in long-term studies and in real-world reports83–86 but interestingly not in asthma94.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [83] Faiz, S. et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. J. Am. Acad. Dermatol. 81, 143–151 (2019). source
This source is a real-world report: the Discussion says its adult atopic-dermatitis cohort had a particularly high rate of conjunctivitis with dupilumab (38.2% versus 8% in a trial meta-analysis). It also notes that conjunctivitis was not observed in the asthma trials it discusses. The citing sentence assigns long-term studies and asthma to other citations; this source supports the real-world portion. (LLM, conf=0.93)
- Supportedcites [84] Abraham, S. et al. Implementation of dupilumab in routine care of atopic eczema. Results from the German national registry TREATgermany. Br. J. Dermatol. 183, 382–384 (2020). source
The Abstract reports conjunctivitis in 13.3% of dupilumab-treated registry patients at three months and 23% at six months, and notes higher rates in other routine-care cohorts. This supports the real-world-report portion attributed to this paper. The asthma comparison is attached to citation 94, not to this source. (LLM, conf=0.87)
- Supportedcites [85] Deleuran, M. et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. J. Am. Acad. Dermatol. 82, 377–388 (2020). source
The Safety section reports conjunctivitis in 10.7% of patients during the long-term dupilumab extension study. The Discussion says these rates were comparable to earlier atopic dermatitis trials, in which conjunctivitis occurred more frequently with dupilumab than placebo. This source supports the long-term-study portion of the citing sentence; separate citations are attached to the real-world and asthma portions. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [86] Wang, C., Kraus, C. N., Patel, K. G., Ganesan, A. K. & Grando, S. A. Real-world experience of dupilumab treatment for atopic dermatitis in adults: a retrospective analysis of patients’ records. Int. J. Dermatol. 59, 253–256 (2020). source
- Supportedcites [94] Bansal, A. et al. Conjunctivitis in dupilumab clinical trials for adolescents with atopic dermatitis or asthma. Am. J. Clin. Dermatol. 22, 101–115 (2021). source
The citation is attached to the asthma comparison, not the preceding claim about long-term and real-world reports. The Discussion says conjunctivitis rates in the adolescent asthma trial were similar for dupilumab- and placebo-treated patients; the Results report no difference between groups in adolescents or adults. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In keratinocytes, IL-22 exerts multiple biological activities, including their proliferation and downregulation of filaggrin expression120,121.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [120] Gutowska-Owsiak, D., Schaupp, A. L., Salimi, M., Taylor, S. & Ogg, G. S. Interleukin-22 downregulates filaggrin expression and affects expression of profilaggrin processing enzymes. Br. J. Dermatol. 165, 492–498 (2011). source
- Partly supportedcites [121] Eyerich, S. et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J. Clin. Invest. 119, 3573–3585 (2009). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) states that IL-22 promotes keratinocyte proliferation and inhibits differentiation. It does not specifically state that IL-22 downregulates filaggrin expression; searches for filaggrin and FLG found no such passage in our copy. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Circulating IL-22 correlates with the severity of AD and appears as a key driver in the inflammatory reaction116,119.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [116] Nograles, K. E. et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J. Allergy Clin. Immunol. 123, 1244–1252 (2009). sourceExperimental — accuracy not yet measured
The Results (page unavailable) correlate the frequency of IL-22-producing CD8+ T cells in AD lesions—not circulating IL-22—with disease severity. The Discussion (page unavailable) suggests an IL-22 contribution to skin changes, but does not establish it as a key driver of the inflammatory reaction. (LLM, conf=0.88)
- Partly supportedcites [119] Gittler, J. K. et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J. Allergy Clin. Immunol. 130, 1344–1354 (2012). sourceExperimental — accuracy not yet measured
The Results section on acute AD reports a positive correlation between lesional IL-22 mRNA and severity (SCORAD), but it was not statistically significant (r=0.55, P=0.132); it does not measure circulating IL-22. The Discussion proposes that IL-22 may contribute to epidermal changes, rather than establishing it as a key driver of inflammation. Page numbers are unavailable in our copy. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A significant part of the sensitization process leading to the generation of IgE responses against environmental allergens (including food allergens)100 as well as against self proteins101 correlates with cutaneous inflammation and overall severity102,103.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [100] Lack, G. Update on risk factors for food allergy. J. Allergy Clin. Immunol. 129, 1187–1197 (2012). source
Citation 100 is attached to environmental allergens, including food allergens, rather than to self proteins or overall AD severity, which have separate citations. In “Data suggesting cutaneous sensitization” (page not supplied), the paper describes food proteins crossing a disrupted skin barrier and leading to IgE production, and links early severe eczema with subsequent food allergy. (LLM, conf=0.90)
- Partly supportedcites [101] Tang, T. S., Bieber, T. & Williams, H. C. Does “autoreactivity” play a role in atopic dermatitis? J. Allergy Clin. Immunol. 129, 1209–1215 (2012). Review paper analysing the evidence for autoimmunity in AD. sourceExperimental — accuracy not yet measured
The ‘How common is autoreactivity in patients with AD?’ section reports correlations between autoreactivity and AD severity, although only two of five analyses found statistically significant correlations. The paper’s discussion of self-protein sensitization also links it to skin inflammation. It does not establish the same severity correlation for IgE responses to environmental allergens; the Abstract says their role in AD persistence is unclear. Page numbers are unavailable in our copy. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [102] Laske, N. & Niggemann, B. Does the severity of atopic dermatitis correlate with serum IgE levels? Pediatr. Allergy Immunol. 15, 86–88 (2004). source
- Partly supportedcites [103] Suarez-Farinas, M. et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J. Allergy Clin. Immunol. 132, 361–370 (2013). sourceExperimental — accuracy not yet measured
The Results (page unavailable) report that total IgE levels correlated with AD severity measured by SCORAD in extrinsic AD, but not intrinsic AD. The Discussion (page unavailable) considers a possible effect of IgE on skin inflammation; it does not establish that effect or show that IgE responses to environmental allergens or self proteins correlate with inflammation or severity. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“T cells are recruited by locally produced chemotactic mediators, and inhibition of their migration represents an appealing strategy18,54,149,150.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [18] Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. & Irvine, A. D. Atopic dermatitis. Nat. Rev. Dis. Prim. 4, 1 (2018). A key review paper on the current understanding of the pathophysiology of AD. source
- Not checked — no full text of the sourcecites [54] Chieosilapatham, P. et al. Keratinocytes: innate immune cells in atopic dermatitis. Clin. Exp. Immunol. 204, 296–309 (2021). source
- Supportedcites [149] Castan, L., Magnan, A. & Bouchaud, G. Chemokine receptors in allergic diseases. Allergy 72, 682–690 (2017). source
The paper reports that chemokines produced by bronchial cells precede the recruitment of Th2 cells (Abstract; page not supplied). Its therapeutic-strategies section describes chemokine receptor antagonists as a treatment approach, while noting that few have become effective treatments. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [150] Abboud, D. & Hanson, J. Chemokine neutralization as an innovative therapeutic strategy for atopic dermatitis. Drug Discov. Today 22, 702–711 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“These mediators are produced in high amounts in AD and correlate with the severity of AD156,157.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [156] Kataoka, Y. Thymus and activation-regulated chemokine as a clinical biomarker in atopic dermatitis. J. Dermatol. 41, 221–229 (2014). source
- Supportedcites [157] Renert-Yuval, Y. et al. Biomarkers in atopic dermatitis-a review on behalf of the International Eczema Council. J. Allergy Clin. Immunol. 147, 1174–1190 (2021). State of the art review paper in the field of biomarker discovery in AD. source
The ‘Biomarkers correlating with clinical severity’ section identifies several TH2-related chemokines whose levels correlate with AD severity, and Table II describes CCL27 as upregulated in AD. The review qualifies that circulating biomarkers are found in moderate-to-severe AD but may not be consistently elevated in mild AD. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“a phase II RCT in AD showed a significant improvement only for the high dose compared with placebo (32% reduction in EASI score versus 11% in the placebo group), but the study was discontinued owing to adverse events131.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [131] Simpson, E. L. et al. A phase 2 randomized trial of apremilast in patients with atopic dermatitis. J. Invest. Dermatol. 139, 1063–1072 (2019). sourceExperimental — accuracy not yet measured
The Clinical efficacy passage reports a 31.6% EASI reduction with apremilast 40 mg twice daily versus 11.0% with placebo at week 12; the 30 mg dose did not reach statistical significance. The Safety section says adverse events, including cellulitis, led to discontinuation of the 40 mg treatment arm—not the study as a whole. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“up to 40% of patients reached the stringent clinical efficacy end point IGA 0/1, in contrast to only 8% in the placebo group, along with a greater decrease in the other secondary end points (EASI, visual analogue scale pruritus and Patient-Oriented Eczema Measure (POEM)) compared with placebo.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Supportedcites [135] Saeki, H., Baba, N., Oshiden, K., Abe, Y. & Tsubouchi, H. Phase 2, randomized, double-blind, placebo-controlled, 4-week study to evaluate the safety and efficacy of OPA- 15406 (difamilast), a new topical selective phosphodiesterase type-4 inhibitor, in Japanese pediatric patients aged 2-14 years with atopic dermatitis. J. Dermatol. 47, 17–24 (2020). source
The Results (Efficacy) report week-4 IGA success of 40.00% in the 1% difamilast group and 8.33% in the vehicle group. The Discussion reports greater improvements in EASI, VAS pruritus and POEM with both difamilast concentrations than with vehicle. The Methods define IGA success as a score of 0 or 1 with at least a two-grade reduction from baseline. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“IL-31 is a prominent pruritogenic cytokine produced by infiltrating TH2 cells in AD and correlates with disease severity97,184,185.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [97] Byeon, J. H. et al. Correlation of serum interleukin-31 with pruritus and blood eosinophil markers in children with atopic dermatitis. Allergy Asthma Proc. 41, 59–65 (2020). source
- Supportedcites [184] Furue, M., Yamamura, K., Kido-Nakahara, M., Nakahara, T. & Fukui, Y. Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis. Allergy 73, 29–36 (2018). source
Section 2 identifies activated TH2 cells and skin-homing T cells as sources of IL-31. Section 5 reports elevated IL-31 expression in atopic dermatitis lesions and states that serum IL-31 levels correlate with disease severity in children and adults. The Conclusion describes IL-31 as important in atopic itch; page numbers were not available in our copy. (LLM, conf=0.90)
- Partly supportedcites [185] Raap, U. et al. Correlation of IL-31 serum levels with severity of atopic dermatitis. J. Allergy Clin. Immunol. 122, 421–423 (2008). sourceExperimental — accuracy not yet measured
In “Correlation of IL-31 serum levels with severity of atopic dermatitis” (page not provided), the authors report that serum IL-31 correlates with AD severity and describe evidence for a role in pruritus. They identify skin-infiltrating T cells as possible sources and report that IL31 mRNA correlates with TH2 cytokines, but do not establish that infiltrating TH2 cells produce IL-31 in AD skin. (LLM, conf=0.85)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Whereas DCs express S1PR1, S1PR3 and S1PR4, T cells display S1PR1 and S1PR4 (refs164–166)”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [164] Bock, S., Pfalzgraff, A. & Weindl, G. Sphingosine 1-phospate differentially modulates maturation and function of human Langerhans-like cells. J. Dermatol. Sci. 82, 9–17 (2016). source
- Partly supportedcites [165] Japtok, L. et al. Sphingosine 1-phosphate modulates antigen capture by murine Langerhans cells via the S1P2 receptor subtype. PLoS ONE 7, e49427 (2012). sourceExperimental — accuracy not yet measured
The Results section says the murine Langerhans-cell line XS52 expresses S1P1–S1P4, supporting S1PR1, S1PR3 and S1PR4 in that DC model, but not establishing this as a general DC expression profile. The Introduction discusses S1P signaling in T-cell movement, but does not say T cells express both S1PR1 and S1PR4. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [166] Blaho, V. A. & Hla, T. An update on the biology of sphingosine 1-phosphate receptors. J. Lipid Res. 55, 1596–1608 (2014). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The mechanisms that underlie itching sensation are complex, involving multiple mediators that initiate the activation of peripheral sensory neurons. They offer a number of potential targets for pharmacological intervention29,180–182.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [29] Mack, M. R. & Kim, B. S. The itch-scratch cycle: a neuroimmune perspective. Trends Immunol. 39, 980–991 (2018). source
- Supportedcites [180] Oetjen, L. K. et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic Itch. Cell 171, 217–228 (2017). Key paper on how immune mediators interact with sensory neurons to induce itching sensation. source
The Introduction identifies several itch-related mediators, including histamine, IL-31, IL-4, and IL-13, and reports that IL-4 and IL-13 directly activate sensory neurons. The Introduction and Discussion also identify neuronal IL-4Rα and JAK1 signaling as potential treatment targets for chronic itch. The supplied passages have section labels but no page numbers. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [181] Erickson, S., Heul, A. V. & Kim, B. S. New and emerging treatments for inflammatory itch. Ann. Allergy Asthma Immunol. 126, 13–20 (2021). source
- Supportedcites [182] Yang, T. B. & Kim, B. S. Pruritus in allergy and immunology. J. Allergy Clin. Immunol. 144, 353–360 (2019). source
“Classical Histaminergic Itch and Beyond” describes multiple itch-inducing molecules binding receptors on sensory nerve endings and triggering neuronal activation. The Conclusions describe a complex interplay of molecular signals and identify several targeted therapies under development. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This strategy has been successfully developed with the S1PR1,3–5 agonist fingolimod167 and the S1PR1,5 agonist siponimod168, which are both approved for the therapy of multiple sclerosis.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Partly supportedcites [167] Chun, J., Kihara, Y., Jonnalagadda, D. & Blaho, V. A. Fingolimod: lessons learned and new opportunities for treating multiple sclerosis and other disorders. Annu. Rev. Pharmacol. Toxicol. 59, 149–170 (2019). sourceExperimental — accuracy not yet measured
The “Fingolimod (Gilenya) for Multiple Sclerosis” section states that fingolimod received FDA approval for relapsing MS. The “Next-Generation Lysophospholipid Receptor Modulators and Diseases” section describes siponimod as having entered clinical trials and reports positive phase III results, but does not say it was approved. Page numbers are unavailable in our copy. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [168] Gajofatto, A. & Turatti, M. Siponimod to treat secondary progressive multiple sclerosis. Drugs Today 56, 37–46 (2020). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, the quest for JAK1-selective compounds resulted in the development of second-generation inhibitors such as upadacitinib and abrocitinib17, for which the regulatory approvals are expected before the end of 2021.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Partly supportedcites [17] Schwartz, D. M. et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat. Rev. Drug Discov. 16, 843–862 (2017). Excellent review on the mode of action of JAK inhibitors. sourceExperimental — accuracy not yet measured
The Figure 3 caption identifies upadacitinib as a newer JAK1-targeting inhibitor, and Table 3 lists it in Phase III trials (page numbers unavailable). Our copy does not name abrocitinib or predict regulatory approvals before the end of 2021, so those parts of the attributed claim are unsupported. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Currently, there are more than 90 patented JAKi, many of which are in clinical development for various indications such as rheumatoid arthritis and inflammatory bowel diseases17,215,216.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Partly supportedcites [17] Schwartz, D. M. et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat. Rev. Drug Discov. 16, 843–862 (2017). Excellent review on the mode of action of JAK inhibitors. sourceExperimental — accuracy not yet measured
Table 3 lists JAK inhibitors in clinical trials for rheumatoid arthritis, ulcerative colitis and Crohn’s disease, supporting the clinical-development portion of the claim. The passages from our copy do not establish that more than 90 JAK inhibitors have been patented. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [215] Schwartz, D. M., Bonelli, M., Gadina, M. & O’Shea, J. J. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat. Rev. Rheumatol. 12, 25–36 (2016). Key review on the link between cytokine receptors and the JAK pathways in autoimmune disorders. source
- Not checked — no full text of the sourcecites [216] Villarino, A. V., Gadina, M., O’Shea, J. J. & Kanno, Y. SnapShot: Jak-STAT signaling II. Cell 181, 1696–1696 (2020). source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recently, JAKi were used successfully in treating the cytokine storm generated by the SARS-CoV-2 virus217.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Partly supportedcites [217] Walz, L. et al. JAK-inhibitor and type I interferon ability to produce favorable clinical outcomes in COVID-19 patients: a systematic review and meta-analysis. BMC Infect. Dis. 21, 47 (2021). sourceExperimental — accuracy not yet measured
The Background (page unavailable) says small studies reinforced the hypothesis that JAK inhibitors could combat high cytokine expression in SARS-CoV-2 infection. The clinical-outcomes section reports lower mortality and ICU admission among treated COVID-19 patients, but the paper does not establish that JAK inhibitors successfully treated cytokine storm itself. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Owing to its particular activity against all JAKs and the spleen tyrosine kinase (SYK), cerdulatinib was initially developed as a systemic therapy for haematological malignancies228.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Partly supportedcites [228] Guo, A. et al. Dual SYK/JAK inhibition overcomes ibrutinib resistance in chronic lymphocytic leukemia: cerdulatinib, but not ibrutinib, induces apoptosis of tumor cells protected by the microenvironment. Oncotarget 8, 12953–12967 (2017). sourceExperimental — accuracy not yet measured
The Research Paper section describes cerdulatinib as an orally available inhibitor of SYK and JAK kinases, and the Discussion reports a clinical trial in patients with CLL and non-Hodgkin lymphoma (page numbers unavailable). The copy supports its activity and investigation as a systemic treatment for haematological malignancies, but does not establish that it inhibits every JAK family member or that this was its initial development purpose. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Delgocitinib (JTE-052/LEO 242549) is a first-generation, non-selective JAK inhibitor that, upon topical and oral application, was shown to improve allergic contact sensitization and AD-like inflammation in animal models221–223.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [221] Amano, W. et al. The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling. J. Allergy Clin. Immunol. 136, 667–677 (2015). source
- Partly supportedcites [222] Tanimoto, A. et al. Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo. Inflamm. Res. 64, 41–51 (2015). sourceExperimental — accuracy not yet measured
The Results section reports that JTE-052 inhibits all four JAK subtypes, supporting its description as a non-selective JAK inhibitor. The paper reports oral effects in mouse cytokine and rat arthritis models, but does not report topical treatment or improvement of allergic contact sensitization or AD-like inflammation; it also does not classify JTE-052 as first-generation. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [223] Yamamoto, Y. et al. Janus kinase inhibitor delgocitinib suppresses pruritus and nerve elongation in an atopic dermatitis murine model. J. Dermatol. Sci. 97, 161–164 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In a phase Ib study with cerdulatinib gel in mild to moderate AD, the compound significantly reduced epidermal thickness, decreased inflammatory DCs and strongly impacted on the inflammatory signature in the transcriptomic analysis232.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Supportedcites [232] Piscitelli, S. C. et al. A Phase 1b, randomized, single-center trial of topical cerdulatinib (DMVT-502) in patients with mild-to-moderate atopic dermatitis. J. Invest. Dermatol. 141, 1847–1851 (2021). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The P2X purinoreceptors 3 (P2XR3) are cation channels expressed in sensory neurons that are activated by extracellular ATP and exert an important role in peripheral irritation, pain sensation, coughing but potentially also in itch207–209.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [207] Dicpinigaitis, P. V., McGarvey, L. P. & Canning, B. J. P2X3-receptor antagonists as potential antitussives: summary of current clinical trials in chronic cough. Lung 198, 609–616 (2020). source
- Not checked — no full text of the sourcecites [208] Inoue, K. & Tsuda, M. Nociceptive signaling mediated by P2X3, P2X4 and P2X7 receptors. Biochem. Pharmacol. 187, 114309 (2020). source
- Partly supportedcites [209] Ford, A. P. & Undem, B. J. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Front. Cell Neurosci. 7, 267v (2013). sourceExperimental — accuracy not yet measured
The Introduction and Abstract describe ATP activation of P2X3-containing receptors on sensory neurons and their role in peripheral irritation and pain. The sensitizing-property section calls them cation channels, and the clinical section reports reduced cough frequency with a P2X3 antagonist. Our copy does not link P2X3 receptors to itch; the only itch mention found is in a reference title. Page numbers are not supplied. (LLM, conf=0.88)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Atopic dermatitis (AD) is the most common chronic inflammatory skin disease1,2.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Introduction
What the sources say
- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The heterogeneous clinical phenotype varies by age, severity and ethnic background5.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Introduction
What the sources say
- Not checked — no full text of the sourcecites [5] Yew, Y. W., Thyssen, J. P. & Silverberg, J. I. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J. Am. Acad. Dermatol. 80, 390–401 (2019). State of the art review on the heterogeneity of the phenotype depending on the ethnic and regional background. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“AD belongs to the spectrum of the atopic disorders, including food allergy, allergic asthma and allergic rhino-conjunctivitis, which are relevant comorbidities10.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Introduction
What the sources say
- Not checked — no full text of the sourcecites [10] Silverberg, J. I. Comorbidities and the impact of atopic dermatitis. Ann. Allergy Asthma Immunol. 123, 144–151 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the complexity of the immune pathways that operate in AD offers the opportunity to explore the potential of bispecific or trispecific antibodies.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Thus, besides efficacy, the long-term safety profile is a key aspect of any new compound in a clinical development programme.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Rests on an assumption: The long-term safety profile is a key aspect of any new compound in a clinical development programme for atopic dermatitis.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A dynamic immune response is the hallmark in AD,”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In a phase I/IIa study in 30 patients (10 adults and 20 children), 60% of the adult patients showed 50% reduction in the Scoring of Atopic Dermatitis (SCORAD), while 90% of the paediatric patients achieved Eczema Area Severity Index (EASI) 50 and 30% achieved EASI90 (see the press release from Forte Bioscience in Related links).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Not matchedcites Forte Bioscience press release
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plainn = 30- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“In a phase II trial, a 2% cream formulation showed significant histological and transcriptional modifications, suggesting a dual impact on the barrier function and the inflammatory reaction44.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Not checked — no full text of the sourcecites [44] Guttman-Yassky, E. et al. ATx201 modulates biomarkers of skin barrier function and cutaneous inflammation in patients with moderate atopic dermatitis. J. Invest. Dermatol. 140, S77 (2020). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Depending on the individual patient’s natural and unpredictable course of the disorder, its management has two main goals: the rapid and efficacious treatment of acute flares and the far more challenging control of the disease in the long term.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“One of the clinical hallmarks of AD is dry, sensitive and highly permeable skin. This phenotypic characteristic is due to disturbance of epidermal barrier function (Box 1) owing to a dual mechanism1,2,18: first, a genetic origin with mutations in genes encoding functionally important structures such as filaggrin (FLG); and second, an inflammatory origin with key mediators such as IL-13 negatively”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the epidermal barrier function
What the sources say
- Not checked — no full text of the sourcecites [1] Weidinger, S. & Novak, N. Atopic dermatitis. Lancet 387, 1109–1122 (2016). source
- Not checked — no full text of the sourcecites [2] Bieber, T. Atopic dermatitis. N. Engl. J. Med. 358, 1483–1494 (2008). source
- Not checked — no full text of the sourcecites [18] Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. & Irvine, A. D. Atopic dermatitis. Nat. Rev. Dis. Prim. 4, 1 (2018). A key review paper on the current understanding of the pathophysiology of AD. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Following the same strategy of bacteriotherapy, topical application of a lyophilized strain of Staphylococcus hominis A9 (ShA9) with the dual activity of killing Staphylococcus aureus and inhibiting the production of S. aureus-derived toxins, allowed the microbiome to recover.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Not checked — no full text of the sourcecites [43] Nakatsuji, T. et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat. Med. 27, 700–709 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A product combining three strains of R. mucosa (FB-401) has been developed and explored, with its therapeutic activity likely consisting of activation of tissue repair and anti-inflammatory activity via Toll-like receptor 5 (TLR5) and tumour necrosis factor receptor (TNFR)42.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Not checked — no full text of the sourcecites [42] Myles, I. A. et al. Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. Sci. Transl Med. 12, eaaz8631 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“The epidermal barrier function is subjected to dual regulation57,252: first, an intrinsic genetic mechanism whereby genes encoding structural elements such as filaggrin (FLG) are subjected to mutations or variants252 and, second, an underlying inflammation that modulates the expression of epidermal structural components253–256 and thereby further aggravates the barrier dysfunction.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets
What the sources say
- Not checked — no full text of the sourcecites [57] Hidaka, T. et al. The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via induction of the neurotrophic factor artemin. Nat. Immunol. 18, 64–73 (2017). Important paper reporting on the role of the xenobiotic receptor AhR in sensing environmental factors to induce AD lesions in an animal model. source
- Not checked — no full text of the sourcecites [252] Irvine, A. D., McLean, W. H. & Leung, D. Y. Filaggrin mutations associated with skin and allergic diseases. N. Engl. J. Med. 365, 1315–1327 (2011). source
- Not checked — no full text of the sourcecites [253] Howell, M. D. et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J. Allergy Clin. Immunol. 120, 150–155 (2007). Shows how the inflammatory reaction impacts on the function of the epidermal barrier in AD. source
- Not checked — no full text of the sourcecites [254] Kim, B. E., Leung, D. Y., Boguniewicz, M. & Howell, M. D. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin. Immunol. 126, 332–337 (2008). source
- Not checked — no full text of the sourcecites [255] Howell, M. D. et al. Th2 cytokines act on S100/A11 to downregulate keratinocyte differentiation. J. Invest. Dermatol. 128, 2248–2258 (2008). source
- Not checked — no full text of the sourcecites [256] Berdyshev, E. et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight 3, e98006 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“While well tolerated, ShA9 also induced a modest improvement of skin lesions as measured by EASI and SCORAD43.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Modulating the skin microbiome
What the sources say
- Not checked — no full text of the sourcecites [43] Nakatsuji, T. et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat. Med. 27, 700–709 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Antigen presentation has a crucial role in the generation and maintenance of the various pathways of the adaptive immune response, ultimately leading to inflammation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“dupilumab is now approved for children aged 6 years and older”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In a phase IIb trial, the best results were obtained with a 1% cream61,62, with 53% of the patients reaching the primary end point of Investigator Global Assessment (IGA) 0/1 versus 28% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not checked — no full text of the sourcecites [61] Paller, A. S. et al. Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis. J. Am. Acad. Dermatol. 84, 632–638 (2020). source
- Not checked — no full text of the sourcecites [62] Peppers, J. et al. A phase 2, randomized dose-finding study of tapinarof (GSK2894512 cream) for the treatment of atopic dermatitis. J. Am. Acad. Dermatol. 80, 89–98 (2019). First report on the improvement of AD upon topical AhR antagonist treatment. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“An interim data analysis from a phase Ib study showed that the compound is well tolerated and provided promising efficacy data, with 67% of the patients achieving EASI75 versus 0% in the placebo group”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites ASLAN press release
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Interestingly, coal tar has been shown to bind to AhR and to restore the expression of filaggrin, as shown by immunohistochemistry and transcriptomic analysis59.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not checked — no full text of the sourcecites [59] van den Bogaard, E. H. et al. Coal tar induces AHR-dependent skin barrier repair in atopic dermatitis. J. Clin. Invest. 123, 917–927 (2013). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In an open-label phase IIa study in eight patients, the safety profile of bermekimab was acceptable, and results for the highest dose indicated promising efficacy, with 39% of patients reaching the status of clear or almost clear (IGA 0/1) as well as a strong reduction in itching, with 68% improvement in the pruritus numerical rating scale (NRS) (see results under NCT03496974).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the innate immune response
What the sources say
- Not matchedcites NCT03496974
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirectn = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“OX40 is a costimulatory molecule and member of the TNF receptor family (TNFRS4).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“It is transiently expressed on T cells upon activation and contributes to clonal expansion, survival and memory formation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
In the paper
“Similarly, in a phase Ib trial, KHK4083 resulted in a 74% reduction in the EASI score, and the IGA 0/1 was reached in 35% of the patients79.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [79] Nakagawa, H. et al. Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis. J. Dermatol. Sci. 99, 82–89 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a phase IIa trial, intravenous GBR 830 was well tolerated and significantly improved the lesions with an EASI50 in 78% of patients who received the antibody, compared with 38% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [78] Guttman-Yassky, E. et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J. Allergy Clin. Immunol. 144, 482–493 (2019). First report on the therapeutic potential of a targeted therapy aiming to impact antigen presentation. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The limitations of this study were small sample size (n = 60) and a time point likely too early to capture the clinical effects.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
hedgedn = 60- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Lebrikizumab does not affect the binding of IL-13 to the IL-13Rα2 receptor chain, the biological role of which remains unclear81.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [81] Gandhi, N. A. et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat. Rev. Drug Discov. 15, 35–50 (2016). Key review paper on the targeted therapy aiming to alter the dominant TH2 pathways in allergic disorders. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Tralokinumab, which was recently backed by a positive opinion from the EMA (EMA/CHMP/202204/2021), is a fully humanized antibody targeting IL-13 that blocks its binding to both IL-13Rα1 and IL-13α2 receptor chains90,91.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [90] Popovic, B. et al. Structural characterisation reveals mechanism of IL-13-neutralising monoclonal antibody tralokinumab as inhibition of binding to IL-13ralpha1 and IL-13Ralpha2. J. Mol. Biol. 429, 208–219 (2017). source
- Not checked — no full text of the sourcecites [91] May, R. D. & Fung, M. Strategies targeting the IL-4/IL-13 axes in disease. Cytokine 75, 89–116 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These encouraging efficacy data were confirmed by reduced use of TCSs as well as improved quality of life in the omalizumab-treated group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“in a first proof-of-concept study of the anti-IL-5 antibody mepolizumab, although eosinophilia was significantly reduced99, the drug failed to demonstrate a significant decrease in the SCORAD, the pruritus scoring or the severity biomarker TARC when compared with baseline.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [99] Oldhoff, J. M. et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy 60, 693–696 (2005). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Eosinophils and their degradation products eosinophil-derived neurotoxin and eosinophil cationic protein are detectable in the inflammatory infiltrate of AD and correlate with disease severity97,98.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [97] Byeon, J. H. et al. Correlation of serum interleukin-31 with pruritus and blood eosinophil markers in children with atopic dermatitis. Allergy Asthma Proc. 41, 59–65 (2020). source
- Not checked — no full text of the sourcecites [98] Kim, H. S. et al. Eosinophil-derived neurotoxin as a biomarker for disease severity and relapse in recalcitrant atopic dermatitis. Ann. Allergy Asthma Immunol. 119, 441–445 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Dupilumab is also approved for atopic comorbidities such as allergic asthma and nasal polyposis”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rate of conjunctivitis was low and the drug was otherwise well tolerated.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although increased IgE serum level is a hallmark of a TH2 immune response and specific IgE to at least one allergen can be found in the vast majority of AD patients”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the phase III pivotal monotherapy studies, at week 16, tralokinumab showed superiority to placebo, with IGA 0/1 being reached in 16% (ECZTRA1) and 22% (ECZTRA2) of the patients receiving the antibody versus 7% and 11% in the respective placebo groups.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Anti-CεmX (FB825) is directed against mIgE and has been reported to deplete IgE-committed B cells and lymphoblasts by apoptosis.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [115] Liour, S. S., Tom, A., Chan, Y. H. & Chang, T. W. Treating IgE-mediated diseases via targeting IgE-expressing B cells using an anti-CεmX antibody. Pediatr. Allergy Immunol. 27, 446–451 (2016). Explains the strategy of depleting IgE-committed B cells by targeting membrane IgE. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The drug is already approved for severe forms of eosinophilic asthma and a phase IIa study in AD exploring its efficacy in a maintenance regimen (HILLIER study) is ongoing.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“benralizumab binds to the IL-5Rα chain expressed on eosinophils and basophils and initiates antibody-dependent cell-mediated cytotoxicity, ultimately leading to their depletion.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In the early 1980s, increased PDE4 activity was described as one of the first candidate targets for the therapy of allergic disorders including AD126,127.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [126] Ungar, B. et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis. J. Allergy Clin. Immunol. 147, 394–397 (2021). source
- Not checked — no full text of the sourcecites [127] Grewe, S. R., Chan, S. C. & Hanifin, J. M. Elevated leukocyte cyclic AMP-phosphodiesterase in atopic disease: a possible mechanism for cyclic AMP-agonist hyporesponsiveness. J. Allergy Clin. Immunol. 70, 452–457 (1982). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Although the highest dose showed an interesting effect on the pruritus score, the absolute change in EASI from baseline was not significant when compared with placebo and thereby not superior to pimecrolimus (NCT01037881).”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites NCT01037881
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“While H4R antagonism alone seems promising in reducing the scratching reaction in animal models of skin inflammation, it only improves inflammation in combination with H1R antagonism147.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [147] Kochling, H. et al. Combined treatment with H1 and H4 receptor antagonists reduces inflammation in a mouse model of atopic dermatitis. J. Dermatol. Sci. 87, 130–137 (2017). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“this compound did not show clinical efficacy or induce any significant changes in several mechanistic investigations such as epidermal thickness, changes in the composition of the cellular infiltrate or analysis of the transcriptomic signatures126.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [126] Ungar, B. et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis. J. Allergy Clin. Immunol. 147, 394–397 (2021). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“administration of the PDE4 inhibitor roflumilast (AQR-151) as a cream failed to reach the primary end point (change in EASI from baseline) and there were no safety signals.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“H3R is localized in the central nervous system, where it regulates the synthesis of histamine.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Four types of histamine receptor (H1R–H4R) have been described, all of which are G protein-coupled receptors137.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [137] Cataldi, M., Borriello, F., Granata, F., Annunziato, L. & Marone, G. Histamine receptors and antihistamines: from discovery to clinical applications. Chem. Immunol. Allergy 100, 214–226 (2014). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“H4R exerts immunoregulatory activities on leukocytes and represents an interesting target for immunomodulation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A phase IIb dose-ranging study with adriforant was terminated and the programme was suspended.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a modest but significant improvement in the SCORAD was shown, but the reduction in pruritus was not significant148.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [148] Werfel, T., Asher, A., Tsianakas, A., Gupta, B. & Sarmiento, R. A phase 2a proof of concept clinical trial to evaluate ZPL-3893787 (ZPL-389), a potent, oral histamine H-4 receptor antagonist for the treatment of moderate to severe atopic dermatitis (AD) in adults. Allergy 71, 95–95 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“H2R is mainly localized in the gastrointestinal tract and other organs, where it regulates smooth muscle relaxation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“H1R in the brain is involved in internal clock modulation, while in the skin, it induces pruritus but also has immunomodulatory activities.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A strategy aimed at enforcing the Treg cell limb of the immune system would restore tolerance and repress chronic inflammation.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
- The authors state this as an assumption: In allergic diseases such as AD, Treg cells do not properly exert their dampening activity, allowing immune polarization.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The pegylated recombinant human IL-2 (rhIL-2; LY3471851) has been designed to target the IL-2 receptor complex on T cells leading to activation and proliferation of Treg cells.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the oral PDE4 inhibitor apremilast is already approved to treat moderate to severe forms of psoriasis while its development in AD fails to progress.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the C-C chemokine receptor 4 (CCR4/CD194) is a hallmark of memory TH2 cells and binds to the chemokines RANTES, MCP1, CCL22/MDC and CCL17/TARC.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The multiple biological activities of S1P are mediated by five distinct G protein-coupled receptors (S1PR1–5), which are differently expressed in various tissues163.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not checked — no full text of the sourcecites [163] Rivera, J., Proia, R. L. & Olivera, A. The alliance of sphingosine-1-phosphate and its receptors in immunity. Nat. Rev. Immunol. 8, 753–763 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Of note, the study included a high proportion of patients with a moderate form of AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“As soon as at week 4, significant changes in peak pruritus NRS (PP-NRS) and the secondary end point EASI75 were observed”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
What the sources say
- Not matchedcites press statement
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although they act initially as S1PR agonists, they promote receptor internalization and so are functional antagonists in the longer term.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although the phase I trial generated promising results for psoriasis, no reports are currently available with regard to its use in AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a repeated-single-dose phase Ib study over 12 weeks in AD, vixarelimab induced a rapid and sustained reduction in pruritus with 53% of the patients having a >4-point reduction in the pruritus score versus 26% in the placebo group.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [194] Mihak, Z. et al. KPL-716, anti-Oncostatin M receptor beta antibody, reduced pruritus in atopic dermatitis [abstract 560]. J. Invest. Dermatol. 139 (Suppl.), S96 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“represent ideal targets for compounds able to modulate their expression on immune cells and thereby prevent lymphocyte migration from lymphatic tissue and reduce the pool of peripheral lymphocytes able to migrate into inflammatory tissues without broad immunosuppression.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“but not at later time points, presumably owing to large background consumption of TCSs191.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the key symptom: itch–scratch cycle
What the sources say
- Not checked — no full text of the sourcecites [191] Silverberg, J. I. et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J. Allergy Clin. Immunol. 145, 173–182 (2020). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Etrasimod (APD334) is a next-generation S1PR agonist that induces sustained internalization of the S1PR1 receptor.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Targeting the adaptive immune response
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a phase II study, this compound provided a significant therapeutic benefit with 72% change (16% for placebo) from baseline of EASI and an IGA 0/1 of 38% versus 8% in the placebo group233.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [233] Kim, B. S. et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J. Allergy Clin. Immunol. 145, 572–582 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The safety profile was comparable to that seen in patients with rheumatoid arthritis with this compound. Acne, upper respiratory tract infections and nasopharyngitis were the most common treatment-emergent adverse events.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [237] Reich, K. et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 397, 2169–2181 (2021). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In terms of efficacy, JAKi have the potential to become game changers in the standard of care for some patients with AD, and their benefit–risk ratio in the AD population seems acceptable.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The JAK family of tyrosine kinases includes four members: JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2)213.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [213] Villarino, A. V., Kanno, Y. & O’Shea, J. J. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat. Immunol. 18, 374–384 (2017). Detailed review on the significance of the JAK–STAT pathway and how to interact with it. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In the monotherapy pivotal trials (Measure Up 1 and 2), upadacitinib showed significant results at week 16 for the primary end point IGA 0/1 (ref.237), along with an early reduction in pruritus and improvement of 4 or more points in the PP-NRS score at week 16.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [237] Reich, K. et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 397, 2169–2181 (2021). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean change in EASI score as well as significantly decreased itch show that cerdulatinib could be a promising alternative to TCSs and topical calcineurin inhibitors.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Viral infections such as herpes simplex and eczema herpeticum as well as headache were more frequent than in the placebo group, and there were only two venous thrombosis events reported.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
What the sources say
- Not checked — no full text of the sourcecites [236] Bieber, T. et al. Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. J. Eur. Acad. Dermatol. Venereol. 35, 476–485 (2020). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Besides considering solely the severity of disease, these alternative approaches could rely on stratification of the AD population according to other dimensions such as phenotypic information, for example, age, age of onset, duration of disease, ethnic background as well as endotypic hallmarks provided by validated biomarkers.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thereby, undertreatment of some individuals at high risk of developing atopic and non-atopic comorbidities as well as the missed opportunity to prevent them by an adequate pharmacological intervention may be substantial.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For systemic therapy, biologics with a slow but pathway-specific mode of action are now competing with small molecules such as JAKi with fast but broader activity.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Interestingly, liver X receptors (LXRα and LXRβ) are ligand-activated nuclear transcription factors that are involved in the regulation of epidermal barrier function and exhibit suppressive effects on skin inflammation241,242, and are therefore potential targets for pharmacological intervention in AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not checked — no full text of the sourcecites [241] Schmuth, M., Moosbrugger-Martinz, V., Blunder, S. & Dubrac, S. Role of PPAR, LXR, and PXR in epidermal homeostasis and inflammation. Biochim. Biophys. Acta 1841, 463–473 (2014). source
- Not checked — no full text of the sourcecites [242] Hashimoto, S., Takanari, H., Compe, E. & Egly, J. M. Dysregulation of LXR responsive genes contribute to ichthyosis in trichothiodystrophy. J. Dermatol. Sci. 97, 201–207 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Atopic dermatitis is characterized by a disturbed epidermal barrier and chronic inflammation.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Identification of the window of opportunity according to the age of the patients for intervention in the skin and gut microbiomes would allow a differential approach using the numerous compounds aimed at correcting the dysbiotic constellation in AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
In the paper
“This is probably relevant for AD243, in which phenotype and/or endotype-based stratification for selection of potential treatment responders with an optimal risk–benefit ratio represents an attractive strategy.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
What the sources say
- Not checked — no full text of the sourcecites [243] Agnihotri, G. & Lio, P. A. Revisiting therapies for atopic dermatitis that failed clinical trials. Clin. Drug Investig. 40, 421–431 (2020). source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sticking to arbitrary cut-off points in the severity scales to define whether a patient deserves systemic therapy may lead to underestimation of the overall systemic impact of inflammation in the skin and a driving force for comorbidities.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The same holds true for the early identification of patients at risk of developing non-atopic comorbidities such as cardiovascular or neuropsychiatric disorders, offering unique opportunities for prevention and risk mitigation strategies.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Another possible explanation for this discrepancy could be related to the inhibition of the biological activity of the JAK2-associated receptor for IL-10, a well-recognized cytokine with anti-inflammatory properties and a key mediator in tolerance induction.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > The broad approach with JAK inhibitors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Although the drug was well tolerated (primary end point reached: number of patients with treatment-related adverse events), the results in terms of clinical improvement (secondary end points) assessed by percentage change in body surface area, percentage change in SCORAD and EASI, were not promising.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not matchedcites NCT02655679
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A better understanding of the biochemical and functional consequences of the genetically driven epidermal barrier dysfunction would enable the design of new skin care products that are better adapted to address the individual needs of a patient, to correct and improve the sensitive and permeable skin in AD.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although biologics may be more adapted for long-term control and potentially disease modification in AD, JAKi provide rapid relief in pruritus and inflammation but, while well tolerated, their benefit–risk ratio remains a significant issue for pharmacovigilance.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, a better understanding of the mechanisms underlying AD has illuminated both the complexity and the systemic impact of this disorder and supported the development of a comprehensive pipeline of new compounds for disease management.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A comparative transcriptomic analysis of skin biopsy samples from a phase I/II study using a topical cream formulation including the penetration enhancer TranscutolP and the LXRβ agonist VTP-38543 (in patients with mild to moderate AD), revealed increased mRNA expression of important epidermal structural proteins (loricrin and filaggrin) as well as improvement of epidermal hyperplasia.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not matchedcites NCT02655679
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Typical biomarkers of AD such as TSLP and CCL17/TARC were also significantly decreased, as was serum IgE240.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Therapeutic strategies and targets > Other inhibitors
What the sources say
- Not checked — no full text of the sourcecites [240] Ghaderpour, A., Kim, Y.-H., Lee, H.-C. & Seong, S.-Y. HY209 ameliorates atopic dermatitis through NF-KB and P38 inhibition. J. Immunol. 204 (Suppl. 1), 147.37 (2020). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the current drug discovery and development strategies still follow the above-mentioned dogma, which may neglect potential preventive and therapeutic approaches.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one. The quote only partly states this claim.
- Rests on an assumption: Treatment guidelines historically prioritized topical anti-inflammatory therapy for mild to moderate atopic dermatitis and reserved systemic approaches for moderate to severe cases.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“If applied early in the natural course of the disorder, some of these products even have the potential to be disease modifiers in that they could impact on the atopic march and other comorbidities.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hence, cost-effectiveness and market access issues tend to become a new hurdle and threat for drug discovery by disincentivizing innovation and hampering patient access.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Progress in our understanding of the manifold epithelial and immunological pathways leading to AD has contributed to the discovery of a remarkable number of therapeutically interesting pathways and targets.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Outlook
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“New and broadly effective compounds such as JAKi have exhibited unprecedented efficacy.”
§ Atopic dermatitis: an expanding therapeutic pipeline for a complex disease > Towards precision medicine for AD > Scientific rationale
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
The paper relies on this without support.
Atopic dermatitis remains challenging to treat because available therapies have limited response.
“AD remains challenging to treat owing to the limited response to available therapies.”
The paper relies on this without support.
More than 70 new compounds are in development for atopic dermatitis.
“there are now more than 70 new compounds in development.”
“More than 70 new compounds are in development and this Review will assess those that are being investigated in clinical trials.”
The paper relies on this without support.
The current therapeutic armamentarium for atopic dermatitis remains very limited and disease management still follows a one-size-fits-all paradigm.
“Despite these recent developments, the current therapeutic armamentarium remains very limited and disease management still follows a ‘one-size-fits-all’ paradigm.”
The paper relies on this without support.
High incidence of atopic dermatitis in the paediatric population, a fluctuating and unpredictable disease course, and a limited armamentarium of approved drugs with an adequate benefit-risk ratio are major challenges in the field.
“In particular, the high incidence of AD in the paediatric population, the highly fluctuating and unpredictable course of disease and the limited armamentarium of approved drugs with an adequate benefit–risk ratio represent major challenges in the field.”
The paper relies on this without support.
The long-term safety profile is a key aspect of any new compound in a clinical development programme for atopic dermatitis.
“Thus, besides efficacy, the long-term safety profile is a key aspect of any new compound in a clinical development programme.”
The authors state this as an assumption.
Affecting the OX40–OX40L interaction influences not only the core TH2 response but also other T cell subsets.
“As it is assumed that affecting the OX40–OX40L interaction affects not only the core TH2 response but also other T cell subsets”
The authors state this as an assumption.
In allergic diseases such as AD, Treg cells do not properly exert their dampening activity, allowing immune polarization.
“Similar to autoimmune disorders, it is assumed that in allergic diseases such as AD, Treg cells do not properly exert their dampening activity, allowing immune polarization.”
The paper relies on this without support.
A TH2 immune response is the core pathway leading to cutaneous inflammation in AD.
“A TH2 immune response is considered the core pathway leading to cutaneous inflammation in AD.”
The paper relies on this without support.
IL-22 binds IL-22R1, which heterodimerizes with IL-10R2; IL-22R1 also associates with IL-20R2 to bind IL-20 and IL-24.
“IL-22 binds to IL-22R1, which subsequently heterodimerizes with IL-10R2. IL-22R1 also associates with IL-20R2 to bind to IL-20 and IL-24”
The paper relies on this without support.
Neurons express receptors for IL-4 and IL-13.
“As neurons express receptors for IL-4 and IL-13”
The paper relies on this without support.
Atopic dermatitis is characterized by a disturbed epidermal barrier and chronic inflammation.
“AD is characterized by a disturbed epidermal barrier and chronic inflammation.”
The authors state this as an assumption.
Prurigo nodularis is related to atopic dermatitis.
“a highly pruritic skin disorder assumed to be related to AD193”
The authors state this as an assumption.
IL-13, IL-22, IL-5 and IL-31 are instrumental in atopic dermatitis.
“cytokines assumed to be instrumental in AD such as IL-13, IL-22, IL-5 and IL-31”
The paper relies on this without support.
Treatment guidelines historically prioritized topical anti-inflammatory therapy for mild to moderate atopic dermatitis and reserved systemic approaches for moderate to severe cases.
“treatment guidelines historically evolved following the established dogma that topical anti-inflammatory therapy is prioritized for mild to moderate forms of AD, while systemic approaches, potentially associated with a higher risk of adverse reactions, are reserved for moderate to severe cases.”
Citations
Cites
Williams, H. C., Leung, D. Y. M., Thestrup‐Pedersen, K., & David, T. J. (2000) · Cited by 4,597
Byrd, A. L., Belkaid, Y., & Segre, J. A. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.157 · Cited by 2,806
Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis
Simpson, E. L., Bieber, T., Guttman-Yassky, E., Beck, L. A., Blauvelt, A., Cork, M. J., Silverberg, J. I., Deleuran, M., Kataoka, Y., Lacour, J.-P., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1610020 · Cited by 2,110
Self-citationWeidinger, S., & Novak, N. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00149-x · Cited by 1,908
Kong, H. H., Oh, J., Deming, C., Conlan, S., Grice, E. A., Beatson, M. A., Nomicos, E., Polley, E. C., Komarow, H. D., Program, N. C. S., et al. (2012) · Genome Research · doi:10.1101/gr.131029.111 · Cited by 1,808
Bieber, T. (2008) · New England Journal of Medicine · doi:10.1056/nejmra074081 · Cited by 1,780
Self-citationWeidinger, S., Beck, L. A., Bieber, T., Kabashima, K., & Irvine, A. D. (2018) · Nature Reviews Disease Primers · doi:10.1038/s41572-018-0001-z · Cited by 1,549
Self-citationJAK inhibition as a therapeutic strategy for immune and inflammatory diseases
Schwartz, D. M., Kanno, Y., Villarino, A., Ward, M., Gadina, M., & O'Shea, J. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.201 · Cited by 1,266
Mechanisms and consequences of Jak–STAT signaling in the immune system
Villarino, A. V., Kanno, Y., & O'Shea, J. J. (2017) · Nature Immunology · doi:10.1038/ni.3691 · Cited by 1,221
Filaggrin Mutations Associated with Skin and Allergic Diseases
Irvine, A. D., McLean, W. H. I., & Leung, D. Y. M. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1011040 · Cited by 1,217
Cited by
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Wang, J., Zhou, Y., Zhang, H., Hu, L., Liu, J., Wang, L., Wang, T., Zhang, H., Cong, L., & Wang, Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01344-4 · Cited by 431
Guttman‐Yassky, E., Renert‐Yuval, Y., & Brunner, P. M. (2025) · The Lancet · doi:10.1016/s0140-6736(24)02519-4 · Cited by 357
Reich, K., Thyssen, J. P., Blauvelt, A., Eyerich, K., Soong, W., Rice, Z. P., Hong, H., Katoh, N., Valenzuela, F., DiBonaventura, M., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01199-0 · Cited by 260
Hu, Y., He, Z., Li, Z., Wang, Y., Wu, N., Sun, H., Zhou, Z., Hu, Q., & Cong, X. (2024) · Clinical Epigenetics · doi:10.1186/s13148-024-01682-2 · Cited by 206
Neuroimmune communication regulating pruritus in atopic dermatitis
Steinhoff, M. S., Ahmad, F., Pandey, A. K., Datsi, A., AlHammadi, A., Al‐Khawaga, S., Al-Malki, A., Meng, J., Alam, M. A., & Buddenkotte, J. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.03.010 · Cited by 201
Metadata
- Authors
- Bieber, T.
- Affiliations
- University Hospital Bonn (DE)
- Corresponding author
- Bieber, Thomas
- ORCID
- Bieber, Thomas
- Venue
- Nature Reviews Drug Discovery
- Published
- 2021-08-20
- Volume
- 21
- Issue
- 1
- Pages
- 21-40
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- PMC
- PMC8377708
- OpenAlex
- W3195786665
- Cited by
- 623
- References
- 269
- Citations by year
- 2026: 106 · 2025: 131 · 2024: 153 · 2023: 128 · 2022: 97 · 2021: 8
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Christine Kühne – Center for Allergy Research and Education
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Keywords
- atopic dermatitis, drug development, dupilumab, tralokinumab, IL-13, JAK1/2 inhibitor, baricitinib, precision medicine, disease mechanisms, clinical phenotype, chronic inflammatory skin disease
- MeSH terms
- Animals, Dermatitis, Atopic, Pharmaceutical Preparations, Humans, Precision Medicine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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