Abstract
BACKGROUND: Atopic dermatitis (AD) often coexists with other type 2 inflammatory diseases. Stapokibart, a humanized IgG4 monoclonal antibody targeting interleukin-4 receptor alpha subunit, showed high efficacy and favorable safety in a phase 3 trial. This post-hoc analysis aimed to compare the efficacy and safety of stapokibart in AD patients with and without type 2 comorbidities. METHODS: During 16-week double-blind period, participants were randomly assigned to stapokibart 600 (loading dose)-300 mg (n = 251) or placebo (n = 249) treatment every other week (Q2W). All patients received stapokibart 300 mg Q2W during subsequent 36-week maintenance period. Patients with ≥ 1 of the following conditions were classified into comorbid subgroup: allergic rhinitis, asthma, food allergies, chronic urticaria, or chronic obstructive pulmonary disease. Post-hoc outcomes included response rates of ≥ 75%/90% improvement in Eczema Area and Severity Index score (EASI-75/90), Investigator's Global Assessment score of 0 or 1 (IGA 0/1) with ≥ 2-point reduction, and ≥ 4-point reduction in weekly average of daily peak pruritus numerical rating scale score (PP-NRS4), and the percentage change from baseline in weekly average of daily PP-NRS score. Treatment-emergent adverse events (TEAEs) were also analyzed by subgroups. RESULTS: Ninety-two patients (36.7%) in stapokibart group and 102 (41.0%) in placebo group had type 2 comorbidities. The demographic characteristics and baseline disease scores were generally comparable across four groups. At week 16, stapokibart demonstrated superior efficacy over placebo in patients with and without type 2 comorbidities. In patients with comorbidities, the response rates of EASI-75, IGA 0/1, and PP-NRS4 in stapokibart and placebo groups were 77.2% versus 26.5%, 55.4% versus 17.6%, and 43.5% versus 12.7%, respectively. In patients without comorbidities, these response rates were 61.0% versus 25.3%, 37.7% versus 15.1%, and 31.4% versus 11.0%, respectively (all p values < 0.0001). All patients showed further improvements in efficacy outcomes during weeks 20-52. TEAEs occurred in 88.8% and 87.7% of comorbid and non-comorbid patients over weeks 0-52. The incidence of conjunctivitis was 5.9% and 5.0%, respectively. CONCLUSION: Stapokibart was effective and safe in adults with moderate-to-severe AD both with and without type 2 comorbidities in both short-term and long-term treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05265923.