Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial

Abstract

Importance: Abrocitinib, an oral, once-daily Janus kinase 1 selective inhibitor, was effective and well tolerated in a phase 3 monotherapy trial of patients with moderate-to-severe atopic dermatitis (AD).

Objective: To investigate the efficacy and safety of abrocitinib in adolescents and adults with moderate-to-severe AD in an identically designed trial.

Design, setting, and participants: This phase 3, double-blinded, placebo-controlled, parallel-group randomized clinical trial included patients 12 years or older with a clinical diagnosis of moderate-to-severe AD for at least 1 year and inadequate response to topical medications given for at least 4 weeks within 6 months. Patients were enrolled from 115 centers in Australia, Bulgaria, Canada, China, Czechia, Germany, Hungary, Japan, South Korea, Latvia, Poland, United Kingdom, and the United States from June 29, 2018, to August 13, 2019. Data were analyzed from September 13 to October 25, 2019.

Interventions: Patients were randomly assigned (2:2:1) to receive once-daily oral abrocitinib in 200- or 100-mg doses or placebo for 12 weeks.

Main outcomes and measures: The coprimary end points were the proportion of patients achieving Investigator Global Assessment (IGA) response (ie, clear [0] or almost clear [1], with improvement of ≥2 grades) and the proportion of patients achieving at least 75% improvement in Eczema Area and Severity Index score (EASI-75) at week 12. Key secondary end points included the proportion of patients achieving a Peak Pruritus Numerical Rating Scale (PP-NRS) response (ie, improvement of ≥4 points) at week 12. Other secondary end points included the proportion of patients achieving at least 90% improvement in EASI score (EASI-90). Safety was assessed via adverse events and laboratory monitoring.

Results: A total of 391 patients (229 male [58.6%]; mean [SD] age, 35.1 [15.1] years) were included in the analysis; of these, 155 received abrocitinib, 200 mg/d; 158, abrocitinib, 100 mg/d; and 78, placebo. Among patients with available data at week 12, greater proportions of patients in the 200- and 100-mg abrocitinib groups vs the placebo group achieved IGA (59 of 155 [38.1%] and 44 of 155 [28.4%] vs 7 of 77 [9.1%]; P < .001) and EASI-75 (94 of 154 [61.0%] and 69 of 155 [44.5%] vs 8 of 77 [10.4%]; P < .001), greater estimated proportions achieved PP-NRS (55.3% [95% CI, 47.2%-63.5%] and 45.2% [95% CI, 37.1%-53.3%] vs 11.5% [95% CI, 4.1%-19.0%]; P < .001), and/or greater proportions achieved EASI-90 (58 of 154 [37.7%] and 37 of 155 [23.9%] vs 3 of 77 [3.9%]) responses. Adverse events were reported for 102 patients (65.8%) in the 200-mg group, 99 (62.7%) in the 100-mg group, and 42 (53.8%) in the placebo group; serious adverse events were reported for 2 patients (1.3%) in the 200-mg group, 5 (3.2%) in the 100-mg group, and 1 (1.3%) in the placebo group. Decreases in platelet count (2 [1.3%]) and laboratory values indicating thrombocytopenia (5 [3.2%]) were reported in the 200-mg group.

Conclusions and relevance: Monotherapy with once-daily oral abrocitinib was effective and well tolerated in adolescents and adults with moderate-to-severe AD.

Trial registration: ClinicalTrials.gov Identifier: NCT03575871.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Silverberg reported serving as an investigator for Celgene Corporation, Eli Lilly and Company, F. Hoffmann-LaRoche, Menlo Therapeutics, Realm Therapeutics PLC, Regeneron Pharmaceuticals, Inc, and Sanofi SA; as a consultant for Pfizer Inc, AbbVie, Inc, Anacor Pharmaceuticals, AnaptysBio, Inc, Arena Pharmaceuticals, Inc, Dermira, Inc, Dermavant Sciences, Eli Lilly and Company, Galderma SA, GlaxoSmithKline, Glenmark Pharmaceuticals, Incyte Corporation, Kiniksa Pharmaceuticals Ltd, LEO Pharma A/S, Menlo Therapeutics, Inc, Novartis International AG, Realm Therapeutics PLC, Regeneron Pharmaceuticals, Inc, and Sanofi SA; and as a speaker for Regeneron Pharmaceuticals, Inc, and Sanofi SA. Dr Simpson reported consulting for Pfizer Inc, AbbVie, Inc, Celgene Corporation, Eli Lilly and Company, Galderma SA, GlaxoSmithKline, LEO Pharma A/S, Menlo Therapeutics, and Regeneron Pharmaceuticals, Inc, and serving as principal investigator for AbbVie, Inc, GlaxoSmithKline, LEO Pharma A/S, Novartis International AG, Regeneron, Pharmaceuticals, Inc, Tioga Pharmaceuticals, and Vanda Pharmaceuticals, Inc. Dr Thyssen reported serving as an advisor, investigator, and/or speaker for Pfizer Inc, AbbVie, Inc, Eli Lilly and Company, LEO Pharma A/S, Regeneron Pharmaceuticals, Inc, and Sanofi Genzyme. Dr Gooderham reported receiving grants, personal fees, and/or nonfinancial support from Pfizer Inc, AbbVie, Inc, Akros Pharma, Inc, Amgen, Inc, Arcutis Biopharmaceuticals, Inc, Bristol-Myers Squibb Company, Boehringer Ingelheim, Celgene Corporation, Coherus BioSciences, Inc, Dermira, Inc, Eli Lilly and Company, Galderma SA, GlaxoSmithKline, Glenmark Pharmaceuticals, Janssen Pharmaceutica, Kyowa Kirin Co, Ltd, LEO Pharma A/S, MedImmune, LLC, Merck & Co, Novartis International AG, Regeneron Pharmaceuticals, Inc, Roche Diagnostics, Sanofi Genzyme, UCB, and Bausch Health Companies, Inc. Dr Chan reported being a shareholder of Pfizer Inc. Dr Feeney reported being a shareholder of Pfizer Inc. Dr Biswas reported being a shareholder of Pfizer Inc. Dr Valdez reported being a shareholder of Pfizer Inc. Dr DiBonaventura reported being a shareholder of Pfizer Inc. Dr Nduaka reported being a shareholder of Pfizer Inc. Dr Rojo reported being a shareholder of Pfizer Inc. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

FAS indicates full analysis set; PPAS, per protocol analysis set; and SAF, safety analysis set.

Figure 2.. Coprimary End Points at Week 12

Data are represented as the percentage of patients achieving Investigator Global Assessment (IGA) response (ie, clear [0] or almost clear [1], with improvement of ≥2 grades) and at least 75% improvement in Eczema Area and Severity Index (EASI-75) score from baseline. IGA response (A) was achieved in 38.1% of patients in the 200-mg group (59 of 155), 28.4% in the 100-mg group (44 of 155), and 9.1% in the placebo group (7 of 77). EASI-75 response (B) was achieved by 61.0% in the 200-mg group (94 of 154), 44.5% in the 100-mg group (69 of 155), and 10.4% in the placebo group (8 of 77). Error bars represent 95% CIs. Conclusion of statistical significance was controlled for multiplicity only at week 12. aP < .05 vs placebo. bP < .001 vs placebo.

Figure 3.. Peak Pruritus Numerical Rating Scale (PP-NRS) Outcomes

A, PP-NRS response is defined as improvement of at least 4 points from baseline. Response was achieved in the 200-mg group by 35.3% of patients at week 2, 52.8% at week 4, and 55.3% at week 12 and in the 100-mg group by 23.1% at week 2, 33.4% at week 4, and 45.2% at week 12 compared with 11.5% of the placebo group at week 12. Conclusion of statistical significance was not controlled for multiplicity at week 8. Error bars indicate 95% CIs. B, Change from baseline in PP-NRS was measured as least-squares mean (LSM). Conclusion of statistical significance was not controlled for multiplicity. Error bars indicate 95% CIs. C, In Kaplan-Meier plot of time to PP-NRS response, plot is based on observed data only (no imputation), and times to event were censored at treatment discontinuation or last observation if response had not been achieved. Twenty events were observed in the placebo group, 90 in the 100-mg group, and 110 in the 200-mg group. aP ≤ .001 vs placebo. bP < .05 vs placebo.