The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index; 27 of the 55 sources its claims cite were checked for support.
Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial
Open accessAbstract
Background Cystic fibrosis transmembrane conductance regulator (CFTR) modulators correct the basic defect caused by CFTR mutations. Improvements in health outcomes have been achieved with the combination of a CFTR corrector and potentiator in people with cystic fibrosis homozygous for the F508del mutation. The addition of elexacaftor (VX-445), a next-generation CFTR corrector, to tezacaftor plus ivacaftor further improved F508del-CFTR function and clinical outcomes in a phase 2 study in people with cystic fibrosis homozygous for the F508del mutation. Methods This phase 3, multicentre, randomised, double-blind, active-controlled trial of elexacaftor in combination with tezacaftor plus ivacaftor was done at 44 sites in four countries. Eligible participants were those with cystic fibrosis homozygous for the F508del mutation, aged 12 years or older with stable disease, and with a percentage predicted forced expiratory volume in 1 s (ppFEV 1) of 40-90%, inclusive. After a 4-week tezacaftor plus ivacaftor run-in period, participants were randomly assigned (1:1) to 4 weeks of elexacaftor 200 mg orally once daily plus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h versus tezacaftor 100 mg orally once daily plus ivacaftor 150 mg orally every 12 h alone. The primary outcome was the absolute change from baseline (measured at the end of the tezacaftor plus ivacaftor run-in) in ppFEV 1 at week 4. Key secondary outcomes were absolute change in sweat chloride and Cystic Fibrosis Questionnaire-Revised respiratory domain (CFQ-R RD) score. This study is registered with ClinicalTrials.gov, NCT03525548. Findings Between Aug 3 and Dec 28, 2018, 113 participants were enrolled. Following the run-in, 107 participants were randomly assigned (55 in the elexacaftor plus tezacaftor plus ivacaftor group and 52 in the tezacaftor plus ivacaftor group) and completed the 4-week treatment period. The elexacaftor plus tezacaftor plus ivacaftor group had improvements in the primary outcome of ppFEV 1 (least squares mean [LSM] treatment difference of 10·0 percentage points [95% CI 7·4 to 12·6], p<0·0001) and the key secondary outcomes of sweat chloride concentration (LSM treatment difference -45·1 mmol/L [95% CI -50·1 to -40·1], p<0·0001), and CFQ-R RD score (LSM treatment difference 17·4 points [95% CI 11·8 to 23·0], p<0·0001) compared with the tezacaftor plus ivacaftor group. The triple combination regimen was well tolerated, with no discontinuations. Most adverse events were mild or moderate; serious adverse events occurred in two (4%) participants receiving elexacaftor plus tezacaftor plus ivacaftor and in one (2%) receiving tezacaftor plus ivacaftor. Interpretation Elexacaftor plus tezacaftor plus ivacaftor provided clinically robust benefit compared with tezacaftor plus ivacaftor alone, with a favourable safety profile, and shows the potential to lead to transformative improvements in the lives of people with cystic fibrosis who are homozygous for the F508del mutation. Funding Vertex Pharmaceuticals.
Overview
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Written from the paper’s full text.
TL;DR
In people with cystic fibrosis homozygous for F508del, elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) produced rapid, clinically robust improvements over TEZ/IVA alone after a 4-week TEZ/IVA run-in. The triple combination was well tolerated over 4 weeks, with no discontinuations and mostly mild or moderate adverse events.
Key findings
- ELX/TEZ/IVA improved ppFEV1 versus TEZ/IVA by a least squares mean difference of 10·0 percentage points (95% CI 7·4 to 12·6, p<0·0001) at week 4.
- Sweat chloride concentration improved by −45·1 mmol/L (95% CI −50·1 to −40·1, p<0·0001), and CFQ-R respiratory domain score improved by 17·4 points (95% CI 11·8 to 23·0, p<0·0001) versus TEZ/IVA.
- In the ELX/TEZ/IVA group, the least squares mean increase in CFQ-R RD score was 16·0 points (95% CI 12·1 to 19·9), exceeding the 4-point minimal clinically important difference.
- Adverse events occurred in 32 (58%) ELX/TEZ/IVA participants and 33 (63%) TEZ/IVA participants; serious adverse events occurred in 2 (4%) versus 1 (2%), with no discontinuations in either group.
Methods
- Phase 3, multicentre, randomised, double-blind, active-controlled trial at 44 sites in Belgium, the Netherlands, the UK, and the USA from 03 August to 28 December 2018; participants were aged ≥12 years, homozygous for F508del, with stable disease and ppFEV1 40–90 inclusive.
- After a 4-week TEZ/IVA run-in, 107 participants were randomised 1:1 to 4 weeks of ELX/TEZ/IVA (n=55) or TEZ/IVA (n=52); the primary endpoint was absolute change from baseline in ppFEV1 at week 4, with key secondary endpoints of sweat chloride and CFQ-R RD score.
- Efficacy was analysed in all randomised participants who received at least one dose, using mixed-effects models for repeated measures with treatment group, visit, treatment-by-visit interaction, baseline ppFEV1, and age as covariates; safety was summarised descriptively.
Limitations
- The paper states that a potential limitation is the 4-week treatment duration, although it was selected because short-term lung function changes with CFTR modulators have been demonstrated within 4 weeks and sustained through 24 weeks, and because safety from the concurrent 24-week heterozygous F508del trial was assumed applicable.
- The paper notes that BMI and weight analyses were not pre-defined, so their p values are nominal and not corrected for multiplicity.
- Evident from the text: the trial used an active control rather than placebo, so comparisons against placebo are inferred from prior TEZ/IVA trials; the sample was small (107 randomised) and long-term safety and durability were not assessed in this 4-week study.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
38 Own result · 11 Not checked yet · 10 Own method · 8 Own interpretation · 7 Supported · 6 Supported so far · 5 Partly supported · 1 Not supported · 1 No full text of the sources · 1 No basis given · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“a potential limitation of this trial is the 4-week duration.7,11,12”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Could not verifycites [7] Ramsey, 2011, A CFTR potentiator in patients with cystic fibrosis and the G551D mutation, N Engl J Med sourceExperimental — accuracy not yet measured
The Methods (Study Subjects; page not provided) describe a 48-week trial, and the Discussion reports outcomes through 48 weeks. Our copy does not assess whether the citing authors’ 4-week trial duration is a limitation (searched: “4-week duration,” “short-term trial,” and “study duration”). (LLM, conf=0.76)
- Disputedcites [11] Wainwright, 2015, Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR, N Engl J Med sourceExperimental — accuracy not yet measured
The Methods (Study Design and Oversight) state that the cited TRAFFIC and TRANSPORT trials administered treatment for 24 weeks, not 4 weeks. The ≤4-week interval in Methods (Study Participants) was between screening and baseline, not the trial duration. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
- Not checked yetcites [12] Taylor-Cousar, 2017, Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del, N Engl J Med source
Checked before — its earlier verdict is held back until a new check runs.
hedged- 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.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Improvements in weight and BMI were not observed in a 24-week study of TEZ/IVA in the same population.12”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Partly supportedcites [12] Taylor-Cousar, 2017, Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del, N Engl J Med sourceExperimental — accuracy not yet measured
The 24-week results (section labeled 2017; Table 2) report no significant BMI difference between the tezacaftor–ivacaftor and placebo groups. They do not report weight change as a separate outcome, and BMI increased modestly in both groups. Thus, the paper supports no treatment-related BMI improvement, but not the full claim that improvements in weight and BMI were not observed. (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
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
“Studies of lumacaftor/IVA and TEZ/IVA showed improvements in lung function (2·6–4·0 percentage points of the percentage of predicted forced expiratory volume in 1 second [ppFEV1]) and decreases in the rate of pulmonary exacerbations (a 35%–39% reduction) in pwCF homozygous for F508del.11,12”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Introduction
What the sources say
- Supportedcites [11] Wainwright, 2015, Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR, N Engl J Med source
The Results > Clinical Efficacy passage reports a 39% lower pulmonary-exacerbation rate for one lumacaftor–ivacaftor dose group versus placebo in the pooled analysis of patients homozygous for Phe508del. This source supports the lumacaftor–ivacaftor part of the jointly cited sentence; it does not need to establish the separately cited tezacaftor–ivacaftor result. (LLM, conf=0.90)
- Not checked yetcites [12] Taylor-Cousar, 2017, Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del, N Engl J Med source
Checked before — its earlier verdict is held back until a new check runs.
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
“Studies of lumacaftor/IVA and TEZ/IVA showed improvements in lung function (2·6–4·0 percentage points of the percentage of predicted forced expiratory volume in 1 second [ppFEV1]) and decreases in the rate of pulmonary exacerbations (a 35%–39% reduction) in pwCF homozygous for F508del.11,12”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Introduction
What the sources say
- Supportedcites [11] Wainwright, 2015, Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR, N Engl J Med source
The Results (Clinical Efficacy) report that lumacaftor–ivacaftor improved the percentage of predicted FEV1 by 2.6–4.0 percentage points versus placebo at week 24. The Methods identify the participants as people with cystic fibrosis homozygous for Phe508del. This paper supports the lumacaftor–ivacaftor portion of the jointly cited claim; it is not offered as the TEZ/IVA study. (LLM, conf=0.94)
- Not checked yetcites [12] Taylor-Cousar, 2017, Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del, N Engl J Med source
Checked before — its earlier verdict is held back until a new check runs.
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
Every source the paper cites for this claim was checked and supports it.
In the paper
“Elexacaftor (ELX; VX-445) is a next-generation CFTR corrector that was shown, in vitro, to significantly increase the amount of mature CFTR protein and CFTR activity when added to the combination of TEZ/IVA.15”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Introduction
What the sources say
- Supportedcites [15] Keating, 2018, VX-445-tezacaftor-ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles, N Engl J Med source
The Abstract Results report that adding VX-445 to tezacaftor–ivacaftor significantly improved CFTR protein processing and chloride transport in vitro compared with any two-agent combination. The Results section (“VX-445–Tezacaftor–Ivacaftor In Vitro”) also reports increased mature CFTR protein and chloride transport with the combination. (LLM, conf=0.93)
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.
- 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
“the resulting mean value is below the diagnostic threshold for CF (figure 3B).18,19”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Efficacy
What the sources say
- Supportedcites [18] Farrell, 2017, Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis Foundation, J Pediatr source
The guideline’s sweat chloride results section states that CF can be diagnosed in individuals with a positive newborn screen, consistent clinical features, or a positive family history when sweat chloride is ≥60 mmol/L. This supports the cited diagnostic threshold; the ELX/TEZ/IVA group mean is attributed to the citing paper’s Figure 3B, not to this guideline. (LLM, conf=0.90)
- Not checked yetcites [19] Castellani, 2018, ECFS best practice guidelines: the 2018 revision, J Cyst Fibros source
Checked before — its earlier verdict is held back until a new check runs.
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
“which is below the diagnostic threshold for CF (60 mmol/L).18”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Supportedcites [18] Farrell, 2017, Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis Foundation, J Pediatr source
The paper’s 'Sweat Chloride Test Results ≥60 mmol/L' section states that a CF diagnosis can be made at ≥60 mmol/L in individuals with a positive newborn screen, consistent clinical features, or a positive family history. The cited claim uses the guideline for that threshold; it does not attribute the week-4 mean of 48.0 mmol/L to the guideline. (LLM, conf=0.92)
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
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Given the multiple defects in F508del-CFTR affecting processing and trafficking, the magnitude of clinical improvements was consistent with the degree of correction of F508del-CFTR by a single CFTR corrector.13,14”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Introduction
What the sources say
- Partly supportedcites [13] Rabeh, 2012, Correction of both NBD1 energetics and domain interface is required to restore ΔF508 CFTR folding and function, Cell sourceExperimental — accuracy not yet measured
The Introduction and Discussion describe modest correction of ΔF508-CFTR by individual corrector molecules and link that limitation to multiple folding defects. They do not compare the degree of molecular correction with the magnitude of clinical improvements, so the clinical-consistency part of the claim is unsupported by this paper. (LLM, conf=0.84)
- Partly supportedcites [14] Mendoza, 2012, Requirements for efficient correction of ΔF508 CFTR revealed by analyses of evolved sequences, Cell sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) reports that single ΔF508 correctors reached only about 15% of wild-type efficacy, and the Discussion (page unavailable) links limited correction of individual folding defects to limited CFTR maturation and function. The paper does not report the magnitude of clinical improvements with a single corrector or compare clinical outcomes with its degree of correction; it expresses concern about whether that degree of correction would provide therapeutic benefit. (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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The 10·0-percentage point improvement in lung function with ELX/TEZ/IVA compared with TEZ/IVA in pwCF homozygous for F508del observed in the current trial is similar to that seen with IVA in pwCF and the G551D mutation.7”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Supportedcites [7] Ramsey, 2011, A CFTR potentiator in patients with cystic fibrosis and the G551D mutation, N Engl J Med source
The Results (Clinical Efficacy; page not provided) report a 10.6-percentage-point improvement in percent predicted FEV1 with ivacaftor versus placebo through week 24 in patients with cystic fibrosis and a G551D mutation. That is similar in magnitude to the citing sentence’s 10.0-percentage-point result; the cited paper is not being used as evidence for the ELX/TEZ/IVA trial itself. (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
“Based on the known impact of the benchmark therapy IVA in a small subset of pwCF, the introduction of ELX/TEZ/IVA is likely to lead to meaningful improvements in the lives of pwCF homozygous for F508del.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Supportedcites [7] Ramsey, 2011, A CFTR potentiator in patients with cystic fibrosis and the G551D mutation, N Engl J Med source
The Results (Clinical Efficacy; page not provided) report improved lung function, fewer pulmonary exacerbations, and better respiratory-symptom scores with ivacaftor in people with cystic fibrosis and a G551D mutation. This supports the cited premise about ivacaftor’s impact in a mutation-defined subset. The prediction about ELX/TEZ/IVA in people homozygous for F508del is the citing authors’ inference, not a finding attributed to this trial. (LLM, conf=0.91)
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.
- Supported
- Probably not a substantial claim. 18
- It may state two separate claims as one. 16
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
“IVA therapy has also been shown to be associated with a decreased need for lung transplant and improved survival with long-term use.22,23”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Supportedcites [22] Bessonova, 2018, Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor, Thorax source
The Results (Death and organ transplantation; page not available) report significantly lower risks of death and transplantation among ivacaftor-treated patients than comparators in the USA in 2014, with similar but non-significant trends in the UK. This supports the claimed association with improved survival and reduced need for transplantation during longer-term use, without establishing causation. (LLM, conf=0.90)
- Not checked yetcites [23] Volkova, 2019, Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries, J Cyst Fibros source
Checked before — its earlier verdict is held back until a new check runs.
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. 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
“Following 24 weeks of IVA therapy, the 10.6 percentage point increase in ppFEV1 and a substantial reduction in pulmonary exacerbations compared with placebo7 were sustained in a 96-week trial.21”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Supportedcites [7] Ramsey, 2011, A CFTR potentiator in patients with cystic fibrosis and the G551D mutation, N Engl J Med source
The Results (Clinical Efficacy) report a 10.6-percentage-point treatment effect in percent-predicted FEV1 through week 24. The Discussion reports a 60% reduction in pulmonary-exacerbation risk versus placebo at 24 weeks. The separate citation after the 96-week statement indicates that statement is not attributed to this source. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [21] McKone, 2014, Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST), Lancet Respir Med source
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The addition of elexacaftor (ELX; VX-445), a next-generation CFTR corrector, to tezacaftor/ivacaftor (TEZ/IVA) further improved F508del-CFTR function and clinical outcomes in a phase 2 study in pwCF homozygous for F508del.”
- Also stated in: § Introduction · hedged
“ELX/TEZ/IVA showed encouraging results in a phase 2 study of this triple combination in a small sample of pwCF homozygous for F508del.15”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Abstract > Background
What the sources say
- Supportedcites [15] Keating, 2018, VX-445-tezacaftor-ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles, N Engl J Med source
The Methods describe a phase 2 trial that included patients homozygous for Phe508del after a tezacaftor–ivacaftor run-in. The Results report that adding VX-445 increased predicted FEV1 by 11.0 percentage points in that group, while the Discussion reports reduced sweat chloride as evidence of improved CFTR function. The supplied passages do not give page numbers. (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.
- Also stated in: § Introduction · hedged
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
“serious adverse events occurred in 4% (n=2) of participants receiving ELX/TEZ/IVA and 2% (n=1) receiving TEZ/IVA.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Abstract > Findings
plainn = 2- 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
“Both rash events in participants receiving ELX/TEZ/IVA resolved during the trial.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Safety
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.
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
“Rash was seen in two (4%) participants in the ELX/TEZ/IVA group and two (4%) participants in the TEZ/IVA group.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Safety
plainn = 4- 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
“Adverse events occurred in 32 (58%) participants in the ELX/TEZ/IVA group and in 33 (63%) participants in the TEZ/IVA group (table 3).”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Safety
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
“No participants in the ELX/TEZ/IVA group and one (2%) in the TEZ/IVA group had an adverse event reported as severe.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Safety
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
“All four participants with rash were female, and all events were mild in severity; none required interruption or discontinuation of trial drugs.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Safety
plainn = 4- 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
“Serious adverse events occurred in two (4%) participants in the ELX/TEZ/IVA group (rash in one participant and pulmonary exacerbation in another) and one (2%) participant in the TEZ/IVA group (pulmonary exacerbation).”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Safety
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
“CFTR dysfunction caused by F508del is multifactorial, with defective protein processing and trafficking to the cell surface, reduced channel gating, and high turnover once at the cell surface.2,9,10”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Introduction
What the sources say
- Not checked — no full text of the sourcecites [2] Dalemans, 1991, Altered chloride ion channel kinetics associated with the delta F508 cystic fibrosis mutation, Nature source
- Not checked — no full text of the sourcecites [9] Welsh, 1993, Dysfunction of CFTR bearing the delta F508 mutation, J Cell Sci Suppl source
- Not checked — no full text of the sourcecites [10] Lukacs, 1993, The delta F508 mutation decreases the stability of cystic fibrosis transmembrane conductance regulator in the plasma membrane. Determination of functional half-lives on transfected cells, J Biol Chem 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
“ELX/TEZ/IVA was generally safe and well tolerated in this 4-week trial.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Safety
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.
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
“Randomisation was stratified by ppFEV1 (<70 vs ≥70, as determined during the run-in period) and age (<18 vs ≥18 years at the screening visit).”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Methods > Randomisation and masking
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.
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 this phase 3 trial in pwCF homozygous for F508del, in which all participants had a 4 week pre-treatment period with TEZ/IVA, treatment with ELX/TEZ/IVA resulted in substantial improvements in lung function, sweat chloride concentration, respiratory-related quality of life, and nutritional parameters compared with TEZ/IVA alone.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
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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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
“Safety was monitored by an independent data monitoring committee.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Methods > Statistical analysis
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.
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
“A hierarchical testing procedure was used to control the overall type I error at an alpha of 0·05 for the primary endpoint and the key secondary endpoints tested.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Methods > Statistical analysis
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.
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
“Following the run-in, 107 participants were randomised and completed the 4-week treatment period.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Abstract > Findings
plainn = 107- 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.
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
“a sample size of 50 participants per treatment group was expected to achieve >90% power to detect a difference of 5 percentage points for the mean absolute change in the ppFEV1 from baseline at week 4 between the two treatment groups.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Methods > Statistical analysis
plainn = 50- 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.
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
“Participants were randomised in a 1:1 ratio by an interactive web response system to either ELX/TEZ/IVA or TEZ/IVA”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Methods > Randomisation and masking
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.
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
“Placebo tablets were used to maintain the blind.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Methods > Randomisation and masking
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.
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
“A phase 3, multi-centre, randomised, double-blind, active-controlled trial of ELX in triple combination with TEZ/IVA (ELX/TEZ/IVA) in pwCF homozygous for F508del was conducted.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Abstract > Methods
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. 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
“ELX/TEZ/IVA was well tolerated, with a safety profile comparable to that in the control group using TEZ/IVA alone.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
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
“To date, clinical results following treatment with IVA in pwCF with the G551D mutation are considered to be the benchmark for treatment with CFTR modulators.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
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.
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
“Because these analyses were not pre-defined, they were not corrected for multiplicity and p values are considered nominal.”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Results > Efficacy
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Pulmonary exacerbations are important life events for pwCF and are associated with a greater rate of lung function decline and decreased survival.24,26”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Not checked yetcites [24] Liou, 2001, Predictive 5-year survivorship model of cystic fibrosis, Am J Epidemiol source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked yetcites [26] Waters, 2012, Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis, Eur Respir J source
Checked before — its earlier verdict is held back until a new check runs.
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.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“Weight and BMI in pwCF are closely correlated with improvements in lung function and are independent predictors of survival.24,25”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Not checked yetcites [24] Liou, 2001, Predictive 5-year survivorship model of cystic fibrosis, Am J Epidemiol source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites [25] Yen, 2013, Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis, J Pediatr 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.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“Weight and BMI in pwCF are closely correlated with improvements in lung function and are independent predictors of survival.24,25”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Not checked yetcites [24] Liou, 2001, Predictive 5-year survivorship model of cystic fibrosis, Am J Epidemiol source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites [25] Yen, 2013, Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis, J Pediatr 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.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“Weight and BMI in pwCF are closely correlated with improvements in lung function and are independent predictors of survival.24,25”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Not checked yetcites [24] Liou, 2001, Predictive 5-year survivorship model of cystic fibrosis, Am J Epidemiol source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked — no full text of the sourcecites [25] Yen, 2013, Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis, J Pediatr 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.
- Not checked yet
None of the sources cited for this claim have been checked yet.
In the paper
“Pulmonary exacerbations are important life events for pwCF and are associated with a greater rate of lung function decline and decreased survival.24,26”
§ Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial > Discussion
What the sources say
- Not checked yetcites [24] Liou, 2001, Predictive 5-year survivorship model of cystic fibrosis, Am J Epidemiol source
Checked before — its earlier verdict is held back until a new check runs.
- Not checked yetcites [26] Waters, 2012, Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis, Eur Respir J source
Checked before — its earlier verdict is held back until a new check runs.
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.
- Not checked yet
The paper relies on this without support.
Treatment with lumacaftor/IVA or TEZ/IVA is standard of care for people with cystic fibrosis homozygous for F508del.
“Because treatment with lumacaftor/IVA or TEZ/IVA is standard of care for pwCF homozygous for F508del, and to ensure a reliable on-treatment baseline before the triple combination treatment period, participants completed a 4-week TEZ/IVA run-in period following a 4-week screening period as described in Taylor-Cousar et al.16”
The paper relies on this without support.
The trial participants are representative of the broader population of people with cystic fibrosis homozygous for F508del.
“ELX/TEZ/IVA provided clinically robust benefit vs TEZ/IVA alone with a favourable safety profile and demonstrates the potential to lead to transformative improvements in the lives of pwCF homozygous for F508del.”
The paper relies on this without support.
Short-term improvements in ppFEV1, sweat chloride, and CFQ-R RD are likely to translate into transformative improvements in the lives of people with cystic fibrosis homozygous for F508del.
“demonstrates the potential to lead to transformative improvements in the lives of pwCF homozygous for F508del.”
The authors state this as an assumption.
The safety profile observed in the concurrent 24-week trial of ELX/TEZ/IVA in pwCF heterozygous for F508del is applicable to pwCF homozygous for F508del.
“the premise that the safety profile observed in the concurrent 24-week trial of ELX/TEZ/IVA in pwCF heterozygous for F508del27 would be applicable to pwCF homozygous for F508del.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The clinical trials with Trikafta showed only partial normalization of the 60%–65% mean baseline ppFEV1 after 24 weeks of treatment in compound heterozygous F508del (16) or at 4 weeks in homozygous F508del patients (15).”
From Allosteric folding correction of F508del and rare CFTR mutants by elexacaftor-tezacaftor-ivacaftor (Trikafta) combination (2020) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In both trials, ELX/TEZ/IVA treatment led to significant improvements in FEV1 % pred, CFQ-R respiratory domain score and sweat chloride concentration.”
From Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one F508del allele: 144-week interim results from a 192-week open-label extension study (2023) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Participants taking ELX/TEZ/IVA in the parent studies had steady and sustained increases in BMI [17, 18].”
From Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one F508del allele: 144-week interim results from a 192-week open-label extension study (2023) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, clinical studies of ELX/TEZ/IVA completed before the start of the pandemic reported similar robust decreases in the frequency of PEx [ 8-10 , 12 ].”
From Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study (2023) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Phase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele.”
From Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study (2023) · cites this paper as [9]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“The restoration of Phe508del CFTR by elexacaftor–tezacaftor–ivacaftor was further confirmed by a concurrent phase 3 trial involving patients with two Phe508del alleles, which showed substantially improved outcomes, including increased lung function and decreased patient-reported respiratory symptoms, as compared with the dual combination of tezacaftor–ivacaftor.32”
From Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele (2019) · cites this paper as [32]
The cited source says what the claim attributes to it.
In the citing paper
“The efficacy and safety of the triple combination of ELX, TEZ and IVA (ELX/TEZ/IVA) were established in two phase 3 pivotal trials in people with CF ≥12 years of age who were heterozygous for F508del and a minimal function mutation (F/MF) or had the F/F genotype [17–19].”
The cited source says what the claim attributes to it.
In the citing paper
“In patients with the F/F genotype, these improvements were superior to those seen with TEZ/IVA.”
The cited source says what the claim attributes to it.
In the citing paper
“In the pivotal Studies 445-102 and 445-103, participants who received ELX/TEZ/IVA had rapid and statistically significant increases in FEV1 % pred and CFQ-R respiratory domain score along with significant decreases in sweat chloride concentration [17, 18].”
The cited source says what the claim attributes to it.
In the citing paper
“A triple combination regimen of elexacaftor (ELX)/TEZ/IVA was shown to be safe and efficacious in patients aged ≥12 years with CF and heterozygous for F508del-CFTR and a minimal function mutation ( F /MF genotypes; Study 445-102) or homozygous for F508del-CFTR ( F/F genotype; Study 445-103) [ 7 , 8 ].”
From EFFECT OF ELEXACAFTOR/TEZACAFTOR/IVACAFTOR ON ANNUAL RATE OF LUNG FUNCTION DECLINE IN PEOPLE WITH CYSTIC FIBROSIS (2023) · cites this paper as [8]
In the citing paper
“the improvements in ppFEV 1 by genotype observed in this study were broadly consistent with what has been reported in ELX/TEZ/IVA Phase 3 clinical trials (14.3, 10.0, and 3.7 percentage points in people with an F /MF genotype, F/F genotype, and F /G and F /RF genotypes, respectively) [ 8 , 9 , 17 ].”
Citations
Cites
Quanjer, P. H., Stanojevic, S., Cole, T. J., Baur, X., Hall, G. L., Culver, B. H., Enright, P., Hankinson, J., Ip, M., Zheng, J., et al. (2012) · European Respiratory Journal · doi:10.1183/09031936.00080312 · Cited by 5,944
Webb, A. K. (2006) · Cited by 4,369
Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele
Middleton, P. G., Mall, M. A., Dřevínek, P., Lands, L. C., McKone, E. F., Polineni, D., Ramsey, B. W., Taylor-Cousar, J. L., Tullis, E., Vermeulen, F., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1908639 · Cited by 2,198
Self-citationA CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation
Ramsey, B. W., Davies, J., McElvaney, N. G., Tullis, E., Bell, S. C., Dřevínek, P., Griese, M., McKone, E. F., Wainwright, C. E., Konstan, M. W., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1105185 · Cited by 2,195
Self-citationElborn, J. S. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00576-6 · Cited by 1,805
Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR
Wainwright, C. E., Elborn, J. S., Ramsey, B. W., Marigowda, G., Huang, X., Cipolli, M., Colombo, C., Davies, J. C., De Boeck, K., Flume, P. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1409547 · Cited by 1,622
Self-citationDiagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation
Farrell, P. M., White, T. B., Ren, C. L., Hempstead, S. E., Accurso, F., Derichs, N., Howenstine, M., McColley, S. A., Rock, M., Rosenfeld, M., et al. (2017) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2016.09.064 · Cited by 953
Self-citationTezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del
Taylor-Cousar, J. L., Munck, A., McKone, E. F., van der Ent, C. K., Moeller, A., Simard, C., Wang, L. T., Ingenito, E. P., McKee, C., Lu, Y., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1709846 · Cited by 794
Self-citationECFS best practice guidelines: the 2018 revision
Castellani, C., Duff, A. J. A., Bell, S. C., Heijerman, H. G. M., Munck, A., Ratjen, F., Sermet-Gaudelus, I., Southern, K. W., Barben, J., Flume, P. A., et al. (2018) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2018.02.006 · Cited by 765
Self-citationPredictive 5-year survivorship model of cystic fibrosis
Liou, T. G., Adler, F. R., FitzSimmons, S. C., Cahill, B. C., Hibbs, J. R., & Marshall, B. C. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.4.345 · Cited by 749
VX-445–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles
Keating, D., Marigowda, G., Burr, L., Daines, C., Mall, M. A., McKone, E. F., Ramsey, B. W., Rowe, S. M., Sass, L. A., Tullis, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1807120 · Cited by 726
Self-citationAltered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation
Dalemans, W., Barbry, P., Champigny, G., Jallat, S., Jallat, S., Dott, K., Dreyer, D., Crystal, R. G., Pavirani, A., Lecocq, J.-P., et al. (1991) · Nature · doi:10.1038/354526a0 · Cited by 707
Quittner, A. L., Modi, A. C., Wainwright, C., Otto, K., Kirihara, J., & Montgomery, A. B. (2009) · Chest · doi:10.1378/chest.08-1190 · Cited by 400
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Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation
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Self-citation
Metadata
- Authors
- Heijerman, H. G. M., McKone, E. F., Downey, D. G., Van Braeckel, E., Rowe, S. M., Tullis, E., Mall, M. A., Welter, J. J., Ramsey, B. W., McKee, C. M., Marigowda, G., Moskowitz, S. M., Waltz, D., Sosnay, P. R., Simard, C., Ahluwalia, N., Xuan, F., Zhang, Y., Taylor-Cousar, J. L., McCoy, K. S., McCoy, K., Donaldson, S., Walker, S., Chmiel, J., Rubenstein, R., Froh, D. K., Neuringer, I., Jain, M., Moffett, K., Taylor-Cousar, J. L., Barnett, B., Mueller, G., Flume, P., Livingston, F., Mehdi, N., Teneback, C., Welter, J., Jain, R., Kissner, D., Patel, K., Calimano, F. J., Johannes, J., Daines, C., Keens, T., Scher, H., Chittivelu, S., Reddivalam, S., Klingsberg, R. C., Johnson, L. G., Verhulst, S., Macedo, P., Downey, D., Connett, G., Nash, E., Withers, N., Lee, T., Bakker, M., Heijerman, H., Vermeulen, F., Van Braeckel, E., Knoop, C., De Wachter, E., van der Meer, R., Merkus, P., & Majoor, C.
- Affiliations
- University College Dublin (IE)
- University of Alabama at Birmingham (US)
- St. Michael's Hospital (CA)
- German Center for Lung Research (DE)
- Seattle Children's Hospital (US)
- Vertex Pharmaceuticals (United States) (US)
- ORCID
- McKone, Edward F
- Rowe, Steven M
- Tullis, Elizabeth
- Mall, Marcus A
- Ramsey, Bonnie W
- Moskowitz, Samuel M
- Waltz, David
- Sosnay, Patrick R
- Ahluwalia, Neil
- Xuan, Fengjuan
- Zhang, Yaohua
- Donaldson, Scott
- Chmiel, James
- Rubenstein, Ronald
- Froh, Deborah K.
- Jain, Manu
- Moffett, Kathryn
- Flume, Patrick
- Jain, Raksha
- Patel, Kapilkumar
- Daines, Cori
- Verhulst, Stijn
- Macedo, Patricia
- Connett, Gary
- Nash, Edward
- Withers, Nicholas
- Lee, Timothy
- Bakker, Marleen
- Knoop, Christiane
- Majoor, Christof
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2019-11
- Volume
- 394
- Issue
- 10212
- Pages
- 1940-1948
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC7571408
- OpenAlex
- W2982296199
- Cited by
- 1,414
- References
- 27
- Citations by year
- 2026: 157 · 2025: 215 · 2024: 210 · 2023: 245 · 2022: 226 · 2021: 204 · 2020: 143 · 2019: 13
- FWCI
- 107.62
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-05-30)
- Open access
- bronze
- doi.org
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- PubMed Central (acceptedVersion)
- Touro Scholar (Touro College) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Research Portal (Queen's University Belfast) (submittedVersion, cc-by-nc-nd)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- National Institutes of Health (P30DK072482, R35HL135816, U54TR001368)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- cystic fibrosis, F508del mutation, elexacaftor, tezacaftor, ivacaftor, CFTR modulators, FEV1, sweat chloride, lung function, treatment safety, adverse events
- MeSH terms
- Adolescent, Aminophenols, Child, Cystic Fibrosis, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Indoles, Male, Pyrazoles, Pyridines, Pyrrolidines, Sweat, Quinolones, Cystic Fibrosis Transmembrane Conductance Regulator, Benzodioxoles, Chloride Channel Agonists
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 2026-11-04, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-04 (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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