Abstract
<jats:p>Introduction Nemolizumab, the first interleukin-31 receptor alpha antagonist, is approved in multiple regions for moderate-to-severe atopic dermatitis (AD; adults and adolescents) and prurigo nodularis (PN; adults). Eczematous events (AD, eczema, nummular eczema) were common in PN pivotal trials (OLYMPIA 1: NCT04501666, OLYMPIA 2: NCT04501679), while no imbalance in AD events was observed in AD trials (ARCADIA 1: NCT03985943, ARCADIA 2: NCT03989349). Objective To characterize cutaneous adverse events (CAEs) associated with nemolizumab using pooled data from four phase 3 trials in AD and PN. Methods This exploratory post-hoc analysis combined data from the initial period of the AD phase 3 trials (the AD pool) and PN phase 3 trials (the PN pool). Frequently reported AEs (≥5% in either arm and indication), and categories/subcategories of defined safety areas of interest (SAOI) were analyzed. Incidence rates, exposure-adjusted incidence rates (EAIR; per 100 patient-years), rate ratio (RR) and 95% CI were calculated without multiplicity adjustment. Investigator-reported AEs were coded using MedDRA v25.0. Results 1135 (AD) and 370 patients (PN) received nemolizumab; 584 (AD) and 186 patients (PN) received placebo. In AD, EAIR were 219.9 (nemolizumab) vs 207.9 (placebo) for any AE (RR 1.1, 95% CI 0.9-1.2) and 5.6 vs 4.0 for SAEs (RR 1.4, 95% CI 0.6-3.3); in PN, 336.0 vs 259.6 for any AE (RR 1.3, 95% CI 1.0-1.6) and 14.8 vs 22.2 for SAEs (RR 0.7, 95% CI 0.3-1.3). The most frequent SAOI in both AD and PN pools was CAEs; EAIR 56.9 (nemolizumab) vs 43.2 (placebo; RR 1.3, 95% CI 1.0-1.7) in AD; 90.7 vs 83.0 (RR 1.1, 95% CI 0.8-1.5) in PN. The most frequent CAE subcategory in both indications was eczema-like CAEs, with AD being the most frequent preferred term in both indications (EAIR 37.5 [nemolizumab] vs 31.0 [placebo; RR 1.2, 95% CI 0.9-1.7] in AD; 38.8 vs 13.1 [RR 3.0, 95% CI 1.5-6.0] in PN). Eczema-like CAEs were mostly rated as mild 36% (nemolizumab) vs 30% (placebo; AD) and 66% vs 56% (PN); and moderate in 48% vs 57% (AD) and 34% vs 33% (PN). The median latency to the first events was 43.5 (nemolizumab) vs 42.0 days (placebo; AD) and 30.0 vs 52.0 days (PN); median duration was 22.0 vs 28.0 days (AD) and 38.0 vs 28.0 days (PN). Events generally resolved by end of the study (AD: 60% [nemolizumab] vs 68% [placebo]; PN: 58% vs 56%), were mostly treated with topical corticosteroids (AD: 31% [nemolizumab] vs 47% [placebo]; PN: 58% vs 44%), and most patients continued with study drug. Conclusion Overall AE and SAE rates were similar with nemolizumab versus placebo. Eczema-like events were generally mild/moderate, resolved with topical corticosteroids and rarely required study-drug discontinuation. These findings support clinicians in anticipating and managing eczema-like events associated with nemolizumab.</jats:p>