Ivarmacitinib ointment for the treatment of adults with mild-to-moderate atopic dermatitis: phase 3 part of a randomized, double-blind, placebo-controlled, phase 2/3 clinical trial

Abstract Background Effective topical therapies for mild-to-moderate atopic dermatitis (AD) should provide rapid itch relief, sustained anti-inflammatory efficacy, and minimal local toxicity. Existing options, including corticosteroids and calcineurin inhibitors, are limited by long-term adverse effects, highlighting the need for safer, steroid-sparing alternatives. Objectives To evaluate the efficacy and safety of ivarmacitinib ointment, a highly selective topical Janus kinase 1 inhibitor, applied twice daily in adults with mild-to-moderate AD. Methods This phase 3 evaluation was part of a multicentre, randomized, double-blind, vehicle-controlled, seamless adaptive phase 2/3 trial conducted at 27 sites in China. Adults aged 18–75 years with Hanifin–Rajka–defined mild-to-moderate AD were randomised (1:1:1) to ivarmacitinib ointment 0.5%, ivarmacitinib ointment 1%, or vehicle for 8 weeks. Patients initially receiving vehicle were re-randomized to active treatment for a blinded extension through Week 52. Co-primary endpoints were Investigator’s Global Assessment (IGA) response (score 0/1 with ≥2-grade improvement) and ≥75% improvement in Eczema Area and Severity Index (EASI-75) at Week 8. Results At week 8, significantly more patients achieved an IGA response with ivarmacitinib than with vehicle (0.5%: 21.3% vs 10.6%, P = 0.0198; 1%: 26.2% vs 10.6%, P = 0.0013); EASI-75 responses were likewise higher (0.5%: 42.6% vs 17.9%; 1%: 45.1% vs 17.9%; both P < 0.0001). Pruritus relief was observed within 48 hours and maintained through week 52, with sustained improvements in SCORAD, affected body surface area, and Dermatology Life Quality Index. During the vehicle-controlled period, treatment-emergent adverse events occurred in 42.6%, 56.6%, and 52.0% of patients in the 0.5%, 1%, and vehicle groups, respectively; most were mild, and infection-related events were infrequent. No treatment-related adverse event occurred in ≥2% of patients in the 1% or vehicle groups, while in the 0.5% group, only folliculitis (4.1%) and increased blood uric acid (3.3%) were reported in ≥2%. No skin atrophy, telangiectasia, or application-site irritation was observed. Long-term safety through week 52 remained consistent, with no new safety signals. Conclusions Twice-daily ivarmacitinib ointment (0.5% or 1%) produced rapid, durable, and well-tolerated improvement in signs, symptoms, and itch in adults with mild-to-moderate AD, supporting its potential as a safe, steroid-sparing topical therapy.