Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 Randomized Clinical Trial

Abstract

Importance: Atopic dermatitis is associated with substantial patient and caregiver burden. Currently available treatments for atopic dermatitis are inadequate or contraindicated for some patients. Abrocitinib (PF-04965842) is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of atopic dermatitis.

Objective: To investigate the efficacy and safety of abrocitinib for patients with moderate to severe atopic dermatitis.

Design, setting, and participants: A phase 2b, randomized, double-blinded, placebo-controlled, parallel-group trial was conducted from April 15, 2016, to April 4, 2017, at 58 centers in Australia, Canada, Germany, Hungary, and the United States among 267 patients 18 to 75 years of age with a clinical diagnosis of moderate to severe atopic dermatitis for 1 year or more and inadequate response or contraindication to topical medications for 4 weeks or more within 12 months. Efficacy was assessed in the full analysis set, which was a modified intention-to-treat population that included all patients who received 1 dose or more of the study drug except for 4 patients from 1 site.

Interventions: Participants were randomly assigned 1:1:1:1:1 to receive abrocitinib (200 mg, 100 mg, 30 mg, or 10 mg) or placebo once daily for 12 weeks.

Main outcomes and measures: The primary outcome was the proportion of patients achieving an Investigator's Global Assessment of clear (0) or almost clear (1) with an improvement from baseline of 2 grades or more at week 12. The secondary outcome was the percentage change from baseline in the Eczema Area and Severity Index at week 12.

Results: Of the 267 participants, 144 were women (mean [SD] age, 40.8 [16.1] years). At week 12, 21 of 48 patients receiving 200 mg of abrocitinib (43.8%; P < .001, 2-sided), 16 of 54 patients receiving 100 mg of abrocitinib (29.6%; P < .001), and 3 of 52 patients receiving placebo (5.8%) achieved grades of clear or almost clear on the Investigator's Global Assessment scale with improvement of 2 grades or more; these rates correspond to maximum effect model-based estimates of 44.5% (95% CI, 26.7%-62.3%) for those receiving 200 mg of abrocitinib, 27.8% (95% CI, 14.8%-40.9%) for those receiving 100 mg of abrocitinib, and 6.3% (95% CI, -0.2% to 12.9%) for those receiving placebo. Reductions in the Eczema Area and Severity Index were 82.6% (90% CI, 72.4%-92.8%; P < .001) for those receiving 200 mg of abrocitinib, 59.0% (90% CI, 48.8%-69.3%; P = .009) for those receiving 100 mg of abrocitinib, and 35.2% (90% CI, 24.4%-46.1%) for those receiving placebo. Adverse events were observed in 184 of 267 patients (68.9%); the most frequently reported adverse events (in ≥3 patients in any group) were dermatitis atopic, upper respiratory tract infection, headache, nausea, and diarrhea. Dose-dependent decreases in platelet count were observed but trended upward toward baseline levels after week 4.

Conclusions and relevance: Once-daily oral abrocitinib was effective and well tolerated for short-term use in adults with moderate to severe atopic dermatitis. Additional trials are necessary to evaluate long-term efficacy and safety.

Trial registration: ClinicalTrials.gov identifier: NCT02780167.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Gooderham reported receiving grants, personal fees, and/or nonfinancial support from AbbVie, Amgen, Akros, Arcutis, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Coherus, Dermira, Eli Lilly, Galderma, Glenmark, Janssen Pharmaceuticals, Kyowa Kirin, LEO Pharma, MedImmune, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Regeneron, UCB, and Valeant. Dr Bissonnette reported receiving grants, personal fees, and/or nonfinancial support from Aquinox Pharma, Antiobix, Asana, Astellas, Brickell Biotech, Dermavant, Dermira, Dignity Sciences, Galderma, Glenmark, GSK-Stiefel, F. Hoffman-La Roche Ltd, LEO Pharma, Neokera, Pfizer, Regeneron, and Vitae; and being a shareholder of lnnovaderm Research. Drs Beebe, Zhang, Banfield, Zhu, Papacharalambous, Vincent, and Peeva reported being employees of Pfizer Inc. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

AE indicates adverse event. aPrimary reasons for screening failure included 30 of 152 patients (19.7%) were not willing or able to comply with study procedures; 19 of 152 patients (12.5%) had evidence of active, latent, or inadequately treated tuberculosis, and 24 of 152 patients (15.8%) had laboratory test result abnormalities. bTwo randomized patients did not receive study treatment and were, therefore, not included in the safety or full analysis set.

Figure 2.. Secondary Efficacy End Points

A, Proportion of patients who achieved Investigator’s Global Assessment (IGA) of clear or almost clear with 2-grade or more improvement from baseline over time. A logistic regression model was used, including treatment as a main effect, baseline IGA as a covariate. B, Percentage change from baseline in Eczema Area and Severity Index (EASI) over time. C, Proportion of patients with baseline pruritus numeric rating scale (NRS) score of 4 or higher, achieving 4-point or more improvement from baseline over time. Mixed-effects model repeated measure was used and contained fixed factors of treatment, week, treatment by week interaction, baseline value, and unstructured covariance matrix. Error bars denote 90% confidence interval. Missing data were not imputed. Baseline was defined as the last measurement before first dosing. Shaded areas represent the follow-up period when patients were no longer receiving the drug.