Upadacitinib Effective for Severe Alopecia Areata in phase 3 trial
A recent clinical trials published in the JAMA Dermatology found that upadacitinib, an oral selective Janus kinase (JAK) inhibitor, had a favorable benefit-risk profile in adults and adolescents with severe alopecia areata (AA), supporting it as a potentially effective treatment option for this population.
The findings come from two parallel phase 3 randomized clinical trials, UP-AA1 and UP-AA2, involved 1,399 participants aged 12 to 64 years. This research evaluated the efficacy and safety of once-daily 15 mg and 30 mg doses of upadacitinib against placebo over a 24-week double-blind treatment period.
The primary endpoint was achieving at least 80% scalp hair coverage by week 24, defined as a Severity of Alopecia Tool (SALT) score of 20 or less. Both doses of upadacitinib met this endpoint with statistically significant improvements over placebo. In UP-AA1, 45.2% of patients receiving 15 mg and 55.0% receiving 30 mg achieved the target, when compared to just 1.5% in the placebo group. Similar results were reported in UP-AA2, where 44.6% and 54.3% of patients in the 15 mg and 30 mg groups, respectively, met the endpoint versus 3.4% receiving placebo.
The patients experienced improvements in eyebrow and eyelash hair, greater rates of complete scalp hair regrowth, faster responses as early as weeks 4, 8 and 12, and meaningful gains in alopecia-specific health-related quality of life. Participants also reported notable improvements in their overall perception of disease severity.
The study enrolled patients with severe disease, with a mean baseline SALT score of 83.9, indicating extensive scalp hair loss. The positive treatment response was consistent across both adults and adolescents. At present, only one systemic therapy is approved for adolescents with severe AA, leaving a substantial unmet clinical need.
The most commonly reported treatment-emergent adverse events included upper respiratory tract infection, acne, elevated blood creatine phosphokinase and nasopharyngitis. Serious adverse events occurred in 1.6% of patients receiving the 15 mg dose and 2.3% receiving the 30 mg dose, when compared to 0.4% in the placebo group. Overall, these findings suggest that upadacitinib demonstrated a favorable benefit-risk profile in both adults and adolescents with severe alopecia areata.
Source:
Mostaghimi, A., Gooderham, M. J., Lynde, C., Sinclair, R., King, B., Hordinsky, M., Rudnicka, L., Guttman-Yassky, E., Serrao, R., Ohyama, M., Zhang, X., Magnolo, N., Kwon, O., Oddi, C., Meerwein, S., Soliman, A. M., Bu, X., Duan, C., Wu, T., … Passeron, T. (2026). Upadacitinib for severe alopecia areata in adults and adolescents: Two phase 3 UP-AA randomized clinical trials: Two phase 3 UP-AA randomized clinical trials. JAMA Dermatology (Chicago, Ill.). https://doi.org/10.1001/jamadermatol.2026.2853
