Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: Results from the open-label run-in period of JADE REGIMEN

Abrocitinib, an oral once-daily Janus kinase 1 selective inhibitor, administered as monotherapy at doses of 200 mg and 100 mg, was well tolerated and more effective than placebo in patients with moderate-to-severe atopic dermatitis (AD) after 12 weeks of treatment in two phase III clinical trials [JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871)] and one phase IIb (NCT02780167) clinical trial. The efficacy and safety of abrocitinib in an induction maintenance paradigm has not been investigated. The objective of this study was to assess the short-term efficacy and safety of abrocitinib monotherapy in the open-label runin period of the JADE REGIMEN study (NCT03627767). In JADE REGIMEN, patients aged ≥ 12 years with moderate-tosevere AD received abrocitinib monotherapy 200 mg for 12 weeks as part of an open-label run-in period before being randomly assigned 1 : 1 : 1 to receive abrocitinib 200 mg, abrocitinib 100 mg or placebo in a 40-week double-blind maintenance period. The analysis of efficacy in the run-in period was evaluated by measuring the proportion of patients who achieved an Investigator\u27s Global Assessment (IGA) response of \u27clear\u27 (0) or \u27almost clear\u27 (1) with ≥ 2- grade improvement, ≥ 75% improvement in Eczema Area and Severity Index (EASI 75 response) and Peak Pruritus Numerical Rating Scale (PP-NRS) (used with permission of Regeneron Pharmaceuticals, Inc. and Sanofi) response with ≥ 4-point improvement (PP-NRS4) at week 12. Patients who achieved IGA and EASI 75 responses during the 12-week run-in period (responders) were randomly assigned 1 : 1 : 1 to receive abrocitinib 200 mg, abrocitinib 100 mg or placebo during the 40-week maintenance period of the study; patients who did not reach this response threshold were considered nonresponders and completed the study at week 12. During the maintenance period, randomly assigned patients who experienced flares of AD (loss of ≥ 50% of EASI response achieved at week 12 with an IGA score ≥ 2) entered a 12-week open-label rescue period. As part of the open-label period, 1233 patients [mean age 31.6 years; 20.0% (n = 246) aged \u3c 18 years; male 55.5%; white 75.5%; moderate AD per IGA 59.1%; severe AD per IGA 40.9%; median EASI score 27.9; median Dermatology Quality of Life Index (DLQI) score 16.0; median Children\u27s DLQI score 12.0] were treated with abrocitinib 200 mg once daily. A total of 120 patients (9.7%) discontinued before week 12, mostly because of adverse events [49 patients (4.0%)] and patient/parent/guardian withdrawal [42 patients (3.4%)]. At week 12, 65.9% [95% confidence interval (CI) 63.3-68.6], 75.6% (95% CI 73.1-78.0) and 68.3% (95% CI 65.3-71.3) achieved IGA, EASI 75 and PP-NRS responses, respectively; 65.2% (95% CI 62.5-67.9) achieved both IGA and EASI 75 responses. In adolescents and adults, the week 12 response rates were 59.8% (95% CI 53.6-65.9) and 67.5% (95% CI 64.6-70.4) for IGA, 71.5% (95% CI 65.9- 77.2) and 76.6% (95% CI 73.9-79.2) for EASI 75, and 57.5% (95% CI 50.0-65.0) and 70.6% (95% CI 67.4-73.8) for PP-NRS4. During the run-in period, 820 patients (66.5%) reported AEs; 20 (1.6%) reported serious AEs, and 38 (3.1%) reported severe AEs. Overall, 798 patients (64.7%) were randomly assigned to the maintenance period at week 12. Abrocitinib monotherapy 200 mg was effective and well tolerated in adolescents and adults with moderateto- severe AD during the 12-week run-in open-label period of JADE REGIMEN. These results support the efficacy and safety observed in the phase III JADE MONO-1 and JADE MONO-2 abrocitinib monotherapy clinical trials