Phase 3 Trial Backs Ivarmacitinib as Effective Oral Option for Moderate to Severe Atopic Dermatitis

"In the phase 3 randomized clinical trial, once-daily oral ivarmacitinib (4 or 8 mg) led to significant improvements in the signs and symptoms of moderate to severe atopic dermatitis in both adolescents and adults, showing a favorable balance between efficacy and safety compared to placebo," the researchers wrote in JAMA Dermatology.

Ivarmacitinib, a selective oral Janus kinase 1 inhibitor, has previously shown promise in managing moderate to severe atopic dermatitis in adults during phase 2 trials. Building on this evidence, Yan Zhao, Department of Dermatology, Peking University People’s Hospital, Beijing, China, and colleagues aimed to assess its efficacy and safety profile in a broader population, including both adolescents and adults affected by moderate to severe AD.

For this purpose, the researchers conducted a multicenter, double-blind, placebo-controlled phase 3 trial across 53 sites in Canada and China, enrolling patients aged 12 to 75 years with moderate to severe atopic dermatitis. Participants were randomly assigned to receive either 4 mg or 8 mg of oral ivarmacitinib or a placebo once daily for 16 weeks.

The main outcomes assessed were the proportion of patients achieving clear or almost clear skin (IGA score of 0 or 1 with at least a 2-grade improvement) and a 75% improvement in Eczema Area and Severity Index (EASI-75) by week 16.

The study led to the following findings:

• A total of 336 patients were randomized, with an average age of 31.1 years; 63.4% were male and 85.1% were Asian. Of these, 113 received 4 mg ivarmacitinib, 112 received 8 mg ivarmacitinib, and 111 received a placebo.
• At week 16, 36.3% of patients on 4 mg and 42.0% on 8 mg ivarmacitinib achieved clear or almost clear skin with at least a 2-grade improvement in IGA score, compared to just 9.0% in the placebo group.
• EASI-75 responses were also better with treatment: 54.0% in the 4 mg group and 66.1% in the 8 mg group, compared to 21.6% in the placebo group.
• Treatment-emergent adverse events were reported in 69.0% of the 4 mg group, 66.1% of the 8 mg group, and 64.9% of the placebo group.
• Serious adverse events were low across all groups, occurring in 2.7% of the 4 mg group, 1.8% of the 8 mg group, and 2.7% of the placebo group.

"These findings highlight ivarmacitinib as a promising and effective oral treatment with a favorable risk-benefit profile for moderate to severe atopic dermatitis, especially in patients who do not respond well to topical therapies," the authors concluded.

Reference:

Zhao Y, Gooderham M, Yang B, et al. Ivarmacitinib for Moderate to Severe Atopic Dermatitis in Adults and Adolescents: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. Published online April 30, 2025. doi:10.1001/jamadermatol.2025.0982