JAK/STAT inhibitors for the treatment of atopic dermatitis
Abstract
Introduction: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Lesional skin of AD contains elevated levels of Th2, Th17, Th22 and Th1-citokines. With a growing movement toward use of targeted therapies, parallel to psoriasis, JAK inhibitors are an important focus of therapeutic research for AD. Methods: We review current evidence on the efficacy and safety of oral and topical JAK inhibitors for the treatment of AD. Results: Several JAK inhibitors are in phase II and III clinical trials as oral therapies for moderate-to-severe AD or as topical treatments for mild-to-moderate AD. Results thus far are encouraging, with the majority of the patients achieving the primary outcome of their trial as well as a favorable safety profile. Discussion: JAK inhibitors will most certainly be the first oral targeted option when topical therapy fails. With good oral bioavailability and lack of immunogenicity, they address some of the limitations of biologics. Yet to be defined is whether selective JAK 1 inhibitors or nonselective JAK inhibitors will provide the best equilibrium of efficacy versus side effects. Less clear is the position in the therapeutic ladder for topical JAK inhibitors; although, an unmeet need exists in the topical treatment of AD.
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The current model does not yet capture inter-patient variability in pharmacological responses or the full chronicity of clinical AD.
“These pharmacological responses are mechanistically consistent with the known mechanisms of these therapeutics, whereas the current model does not yet capture inter-patient variability in pharmacological responses or the full chronicity of clinical AD [46][47][48] .”
From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [47]
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“Additionally, numerous JAK inhibitors are in various phases of clinical testing for both psoriasis (55) and AD (59).”
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“These mechanisms contribute significantly to rapid itch reduction seen in AD using both topical and oral JAK inhibitors [44].”
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“Dupilumab, the first biologic approved as a first-line treatment for moderate-to-severe AD, is an interleukin (IL)-4 receptor antagonist that inhibits IL-4 and IL-13 signalling and showed promising efficacy.7 Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway (JAK–STAT pathway) are…”
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“JAK inhibitors are positioned to become the first oral targeted options when topical therapy fails (Table 2) [20], although are unlikely to be first-line for most children eligible for dupilumab.”
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“Based in preliminary phase II data, upadacitinib (a selective JAK1 inhibitor) seems to achieve even better outcomes than dupilumab (21).”
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BackgroundJAK inhibitors in the treatment of atopic dermatitis
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“2 TSLP and IL‐31 induce JAK1 and JAK2 expression, which activate STAT5.”
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“In recent years, based on a deeper understanding of the molecular pathways in AD pathogenesis, targeted biologics (e.g., the anti-IL-4/IL-13 receptor monoclonal antibody Dupilumab) and small-molecule JAK-STAT inhibitors have shown great promise and have been approved for clinical use (19, 20).”
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“Organization Global Burden of Diseases at least 230 million people worldwide suffer from AD.((4)) The prevalence of AD in children is about 10% to 20% whereas in adults it is about 5-10%.”
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“Furthermore, inhibiting the JAK/STAT pathway may help with chronic dermatitis, and p38 MAPK may regulate inflammatory diseases by enhancing the NF-κB signaling (33-35).”
BackgroundMaterial engineering for atopic dermatitis treatment
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HPV‐6 Positive Eruptive Verruca Vulgaris After Upadacitinib Initiation for Severe Atopic Dermatitis
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Baricitinib in Dermatology: Expanding Therapeutic Horizons Beyond Alopecia Areata
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- Authors
- Rodrigues, M. A., & Torres, T.
- Affiliations
- Department of Dermatology, Centro Hospitalar e Universitário do Porto, Porto, Portugal;
- Universidade do Porto (PT)
- Corresponding author
- Torres, Tiago
- Venue
- Journal of Dermatological Treatment
- Publisher
- Informa UK Limited
- Published
- 2019-02-18
- Volume
- 31
- Issue
- 1
- Pages
- 33-40
- ISSN
- 0954-6634 (ISSN-L)
- 1471-1753
- OpenAlex
- W2913292104
- Cited by
- 97
- References
- 0
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 17 · 2023: 18 · 2022: 19 · 2021: 20 · 2020: 5 · 2019: 5
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Dermatological Treatment (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- atopic dermatitis, JAK inhibitors, JAK/STAT signaling, topical JAK inhibitor, oral JAK inhibitor, targeted therapy, Th2 cytokines, Th17 cytokines, JAK1 inhibitor, treatment efficacy and safety
- MeSH terms
- Janus Kinase Inhibitors, Administration, Oral, Administration, Topical, Clinical Trials as Topic, Dermatitis, Atopic, Humans, Severity of Illness Index, Treatment Outcome, STAT Transcription Factors, Janus Kinase 1
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