Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Atopic Dermatitis

Abstract

Importance: Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown. Objective: To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis. Design, Setting, and Participants: Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2). Interventions: Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner. Main Outcomes and Measures: Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed. Results: Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals. Conclusions and Relevance: In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks. Trial Registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2).