Dataset Information

Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

ABSTRACT:

Background

Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200 mg and 100 mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch response (with abrocitinib 200 mg) than dupilumab at week 2.

Objective

This study assessed the efficacy and safety of abrocitinib and dupilumab in a subset of patients with severe and/or difficult-to-treat AD in a post hoc analysis of the JADE COMPARE trial.

Methods

Adults with moderate-to-severe AD received once-daily oral abrocitinib 200 mg or 100 mg, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo with concomitant medicated topical therapy. Severe and/or difficult-to-treat AD subgroups were classified by baseline characteristics [Investigator's Global Assessment (IGA) 4, Eczema Area and Severity Index (EASI) > 21, failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids), percentage of body surface area (%BSA) > 50, upper quartiles of EASI (EASI > 38) and %BSA (%BSA > 65), and combined subgroup of IGA 4, EASI > 21, and %BSA > 50, and failure or intolerance to prior systemic agents (excluding patients who took only corticosteroids)]. Assessments included IGA score of 0 (clear) or 1 (almost clear) and a ≥ 2-point improvement from baseline, ≥ 75% and ≥ 90% improvement from baseline in EASI (EASI-75 and EASI-90), ≥ 4-point improvement from baseline in Peak Pruritus-Numerical Rating Scale (PP-NRS4), time to PP-NRS4, least squares mean (LSM) change from baseline in 14-day PP-NRS (days 2-15), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI) up to week 16.

Results

The proportion of patients achieving IGA 0/1, EASI-75, and EASI-90 responses was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.05) across all subgroups with severe and/or difficult-to-treat AD. Across most subgroups, PP-NRS4 response was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.01); the time to achieve this response was shorter with abrocitinib 200 mg (range 4.5-6.0 days) than abrocitinib 100 mg (range 5.0-17.0 days), dupilumab (range 8.0-11.0 days), and placebo (range 3.0-11.5 days). LSM change from baseline in POEM and DLQI was significantly greater with abrocitinib 200 mg than placebo (nominal p < 0.001) across all subgroups. Clinically meaningful differences were observed between abrocitinib and dupilumab for most evaluated endpoints across several subgroups, including in patients who failed or were intolerant to prior systemic therapy.

Conclusions

Abrocitinib provided rapid and substantially greater improvements in skin clearance and quality of life compared with placebo and dupilumab in subgroups of patients with severe and/or difficult-to-treat AD. These findings support the use of abrocitinib for severe and/or difficult-to-treat AD.

Trial registration

ClinicalTrials.gov, NCT03720470.

SUBMITTER: Simpson EL

PROVIDER: S-EPMC10293387 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

Simpson Eric L EL Silverberg Jonathan I JI Thyssen Jacob P JP Viguier Manuelle M Thaçi Diamant D de Bruin-Weller Marjolein M Weidinger Stephan S Chan Gary G DiBonaventura Marco M Biswas Pinaki P Feeney Claire C Koulias Christopher C Cork Michael J MJ

American journal of clinical dermatology 20230522 4

<h4>Background</h4>Traditional systemic immunosuppressants and advanced therapies improve signs and symptoms of moderate-to-severe atopic dermatitis (AD). However, data are limited in severe and/or difficult-to-treat AD. In the phase 3 JADE COMPARE trial of patients with moderate-to-severe AD receiving background topical therapy, once-daily abrocitinib 200 mg and 100 mg showed significantly greater reductions in the symptoms of AD than placebo and significantly greater improvement in itch respon ...[more]

PMID: 37213005

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Project description:IntroductionPrimary results of the JADE DARE trial (NCT04345367) demonstrated that abrocitinib was superior to dupilumab in reducing the signs and symptoms of moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with moderate-to-severe AD who were responders or nonresponders to dupilumab using various definitions of response.MethodsData included dupilumab-treated patients from JADE DARE who switched to abrocitinib 200 mg when enrolled in the ongoing JADE EXTEND trial (NCT03422822). For this analysis, various response criteria at Week 26 of JADE DARE were defined post hoc based on Investigator's Global Assessment (IGA), Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (PP-NRS), and Dermatology Life Quality Index (DLQI) scores or responses. Efficacy was analyzed at Week 12 of JADE EXTEND based on patients' fulfillment of the various response criteria at Week 26 of JADE DARE. EASI scores and percentage changes from baseline in EASI and PP-NRS at Week 26 in JADE DARE were compared with the corresponding scores and percentage changes at Week 12 in EXTEND. Safety was assessed.ResultsOf 365 dupilumab-treated patients in JADE DARE, 316 were enrolled in JADE EXTEND and 312 received abrocitinib 200 mg. Most dupilumab responders for IGA, EASI, PP-NRS, and DLQI at DARE Week 26 maintained their responses 12 weeks after switching to abrocitinib, while a considerable proportion of IGA, EASI, PP-NRS, or DLQI dupilumab nonresponders gained response after switching to abrocitinib. Lower EASI scores and greater percentage changes from baseline in EASI and PP-NRS scores were observed with abrocitinib at EXTEND Week 12 than with dupilumab at DARE Week 26. No new safety signals were observed.ConclusionAbrocitinib 200 mg may be an effective treatment option for patients with moderate-to-severe AD who do not achieve an optimal response with dupilumab treatment.Clinical trial registrationClinicaltrials.gov: NCT04345367 (JADE DARE) and NCT03422822 (JADE EXTEND).

Project description:IntroductionAtopic dermatitis (AD) can affect multiple body regions and is especially burdensome when involving exposed skin areas. Rapid, effective treatment of AD across body regions remains an unmet need, particularly for difficult-to-treat areas such as the head and neck area. We investigated the temporal and regional patterns of clinical improvement in AD with the use of abrocitinib, an orally available Janus kinase 1 selective inhibitor under development for the treatment of moderate-to-severe AD.MethodsWe performed a post hoc analysis of data from JADE COMPARE, a phase 3, multicenter, randomized, double-blind, double-dummy trial that evaluated the efficacy and safety of abrocitinib 200 mg once daily, abrocitinib 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, and placebo in adult patients with moderate-to-severe AD who were concomitantly receiving medicated topical therapy. Assessments included the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD) index.ResultsWith abrocitinib 200 mg, time to ≥ 75% improvement in EASI (EASI-75) occurred at a median of 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, EASI-75 response was achieved at a median of 30-32 days for the trunk and lower limbs, and at 56-57 days for the head and neck region and upper limbs. With dupilumab, EASI-75 response was achieved at a median of 43 days for the trunk and 57 days for other regions. EASI body region scores significantly improved with abrocitinib 200 mg and 100 mg versus placebo at week 2 (p < 0.0001 for all comparisons). Improvements with abrocitinib were maintained up to week 16.ConclusionsRapid and persistent improvement in AD across all body regions was observed with abrocitinib treatment. Abrocitinib may be useful in patients with AD that affects difficult-to-treat anatomical areas or who require a rapid response.Trial registrationClinicaltrials.gov identifier: NCT03720470.

Project description:BackgroundAbrocitinib, an oral Janus kinase 1 inhibitor, provided significant itch relief by week 2 in patients with moderate-to-severe atopic dermatitis (AD) in the phase III JADE COMPARE trial.ObjectivesThis post-hoc analysis of JADE COMPARE aimed to further characterize itch response and determined whether early itch relief could predict subsequent improvements in AD severity.MethodsJADE COMPARE was a randomized, double-blind, double-dummy, placebo-controlled trial. Adult patients (aged ≥ 18 years) with moderate-to-severe AD were randomly assigned to receive oral abrocitinib 200 mg or 100 mg once daily, subcutaneous dupilumab 300 mg every other week (after a 600-mg loading dose), or placebo, plus medicated topical therapy for 16 weeks. Assessments were ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) from days 2 to 15, Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA) response, and Dermatology Life Quality Index (DLQI) scores at week 12. Association between week 2 PP-NRS4 and efficacy at week 12 was evaluated by chi-squared tests. The predictive value of early response for later efficacy was assessed by area under the receiver operating characteristic curve.ResultsAs early as day 4 after treatment, a significantly greater proportion of patients achieved PP-NRS4 response with abrocitinib 200 mg (18.6%) versus dupilumab (5.6%; p < 0.001) and placebo (6.0%; p < 0.003). A similar trend was observed with abrocitinib at the 100-mg dose, with significantly greater PP-NRS4 response rates versus placebo as early as day 9. With both doses of abrocitinib, week 12 IGA 0/1, EASI-75, EASI-90, and DLQI 0/1 response rates were greater in week 2 PP-NRS4 responders than nonresponders; no differences were observed between week 2 PP-NRS4 responders and nonresponders in the dupilumab and placebo groups. Early improvement in PP-NRS at week 2 was associated with skin clearance at week 12 in abrocitinib-treated patients.ConclusionsAbrocitinib resulted in rapid relief from itch in patients with moderate-to-severe AD, with significant improvement in itch as early as day 4 after treatment with abrocitinib 200 mg compared with dupilumab and placebo. Abrocitinib-induced itch relief by week 2 was associated with subsequent improvements at week 12. [Video abstract available.] TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03720470. Early itch response with abrocitinib is associated with later efficacy outcomes in patients withmoderate-to-severe atopic dermatitis: subgroup analysis of the randomized phase III JADE COMPARE trial (MP4 335,375kb).

Project description:ImportanceDupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD.ObjectiveTo investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD.Design, setting, and participantsThe phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion.InterventionsPatients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy.Main outcomes and measuresCoprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored.ResultsThis study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P < .05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P < .05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P < .01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs.Conclusions and relevanceThis randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile.Trial registrationClinicalTrials.gov identifier: NCT03796676.

Project description:IntroductionEarly prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12 efficacy based on week 4 responses in patients receiving abrocitinib 100 mg/day and assessed the effect of an abrocitinib dose increase on platelet counts.MethodsAnalysis included the phase 3 trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), and TEEN (NCT03796676). For platelet counts and simulations, a phase 2 psoriasis trial (NCT02201524) and phase 2b (NCT02780167) and phase 3 (MONO-1, MONO-2, and REGIMEN (NCT03627767)) abrocitinib trials were pooled. A training-and-validation framework assessed potential predictors of response at week 4: score and score change from baseline in the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS), and percentage change from baseline in EASI. The dependent variables at week 12 were ≥ 75% improvement in EASI (EASI-75) and IGA score of 0 (clear) or 1 (almost clear) and ≥ 2-point improvement from baseline. The probability of each variable to predict week 12 EASI-75 and IGA responses was calculated.ResultsIn the training cohort (n = 453), 72% of the ≥ 50% improvement in EASI (EASI-50) at week 4 responders and 16% of the nonresponders with abrocitinib 100 mg achieved EASI-75 at week 12; 48% and 6% of the week 4 EASI-50 responders and nonresponders, respectively, achieved week 12 IGA response. Similar results occurred with week 4 IGA = 2, ≥ 4-point improvement from baseline in PP-NRS, or EASI = 8 responders/nonresponders. Platelet counts after an abrocitinib dose increase from 100 to 200 mg were similar to those seen with continuous dosing with abrocitinib 100 mg or 200 mg.ConclusionAchieving week 4 clinical responses with abrocitinib 100 mg may be useful in predicting week 12 responses. Week 4 nonresponders may benefit from a dose increase to abrocitinib 200 mg, and those that receive this dose increase are likely to achieve treatment success at week 12, with no significant impact on platelet count recovery. Video abstract available for this article.Clinical trial registrationNCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767.

Project description:IntroductionAtopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, painful, and dry skin. Despite the great number of available therapies, economic evaluations are still needed to provide evidence on their cost efficiency. This research aimed to evaluate the cost effectiveness of the Janus kinase (JAK) inhibitor abrocitinib (200 mg) compared with dupilumab (300 mg), tralokinumab (300 mg), baricitinib (2 and 4 mg), and upadacitinib (15 and 30 mg) for the treatment of patients with severe AD from the Spanish National Health System (NHS) perspective.MethodsA hybrid model consisting of a decision tree linked to a Markov model was developed to estimate costs, quality-adjusted life-years (QALYs), total years in response and incremental cost-per-QALY gained (willingness-to-pay [WTP] threshold: €25,000/QALY). Adults with severe AD entered the decision tree and response (75% reduction in baseline Eczema Area and Severity Index score, EASI-75) was considered at 16 and 52 weeks. After this time, patients entered the Markov model (remainder of the 10-year time horizon), which consisted of three health states: maintenance with active therapy, subsequent treatment, or death. All costs were presented in 2022 euros (€). Additionally, cost per number-needed-to-treat (NNT) was calculated for abrocitinib and dupilumab based on a head-to-head post-hoc analysis.ResultsAbrocitinib 200 mg was dominant (i.e., lower incremental costs and higher incremental benefit) compared with all studied alternatives (dupilumab 300 mg, tralokinumab 300 mg, baricitinib 2 and 4 mg, upadacitinib 15 and 30 mg) with a QALYs gain of 0.49, 0.60, 0.64, 0.43, 0.45, and 0.08, respectively, and per-person costs savings of €22,097, €24,140, €14,825, €7,116, €12,805, and €45,189, respectively. Considering the WTP threshold, abrocitinib was dominant or cost effective compared with all alternatives for most simulations. Additionally, abrocitinib was dominant compared with all alternatives when evaluating the cost effectiveness over a 5-year time horizon. NNT showed that abrocitinib was dominant versus dupilumab.ConclusionsThe results of the study show that abrocitinib is a cost-effective therapy compared with other JAK inhibitors and biological therapies from the Spanish NHS perspective.

Dataset Information

Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

Background

Objective

Methods

Results

Conclusions

Trial registration

Publications

Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial.

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