Efficacy and safety of upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: A subgroup analysis of the Measure Up 1, Measure Up 2 and AD Up phase III clinical trials

Atopic dermatitis (AD) is a chronic, recurrent, highly pruritic immune-mediated inflammatory disease, with an unmet need for additional effective therapies. Results from phase IIb and phase III clinical trials demonstrated that upadacitinib (UPA) was efficacious with a favourable benefit-risk profile vs. placebo (PBO) in the treatment of moderate-to-severe AD. Here, we analyse the efficacy and safety of UPA in adolescent and adult subgroups using data from three phase III studies. Data from three randomized, double-blind, placebo-controlled, multicentre phase III studies [Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422) and AD Up (NCT03568318)] were used to assess the efficacy and safety of UPA in adolescents and adults. Across the three studies, adolescents (aged 12 to 55%), and numerically greater proportions of patients achieved EASI-75 for UPA30 (> 72%), with response rates for both UPA doses demonstrating significantly better efficacy than PBO (≥ 30%). vIGA-AD 0/1 was achieved by > 38% and > 50% of patients receiving UPA15 and UPA30, respectively, in both subgroups, with response rates for both UPA doses demonstrating significantly better efficacy than PBO ( 33% of adolescents and > 42% of adults receiving UPA15 vs. > 50% of adolescents and > 60% of adults receiving UPA30, with response rates for both UPA doses demonstrating significantly better efficacy than PBO ( 13% (UPA15) and ≥ 19% (UPA30) of adolescents aged 12 to 24% and > 37% receiving UPA15 and UPA30, respectively, both significantly greater than PBO. Achievement of HADS-A 41% for UPA30 in both subgroups. Rates of serious AEs and AEs leading to discontinuation were generally similar across treatment groups for both adolescents and adults. Rates of acne-the most common AE-were higher with UPA than PBO, and similar for adolescents and adults. Serious infections were reported infrequently (< 1%) with UPA in both adolescents and adults. Opportunistic infections were reported in < 1% of adults, with n ne in adolescents. Rates of herpes zoster virus infection were higher with UPA than PBO in both adolescents and adults. No adjudicated gastrointestinal perforation, major adverse cardiovascular events or venous thromboembolic events were reported in the UPA groups. No malignancies were reported in adolescents. Adolescent and adult responses to UPA15 and UPA30 treatment were consistent across clinical, quality-of-life and patient-reported outcome assessments, with similar and acceptable safety in both populations.