Upadacitinib delivers substantial hair regrowth in severe alopecia areata

Clinical takeaway: In adults and adolescents with severe alopecia areata, once-daily upadacitinib produced substantial regrowth by 24 weeks, with responses emerging as early as 8 weeks and a safety profile consistent with previous experience with the drug.

Treatment options for severe alopecia areata remain limited, particularly for adolescents. These data suggest upadacitinib could offer a new oral option with rapid and clinically meaningful hair regrowth.

Two global phase 3 trials (UP-AA1 and UP-AA2) randomized 1,399 patients aged 12 to 64 years with severe alopecia areata (baseline Severity of Alopecia Tool [SALT] score ≥50; mean SALT score 84) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 24 weeks. Most participants had longstanding disease, and nearly half had very severe alopecia.

The primary endpoint, achieving a SALT score ≤20 (reflecting at least 80% scalp hair coverage), was met by 45% of patients receiving upadacitinib 15 mg and 54% to 55% receiving 30 mg, compared with just 2% to 3% of placebo-treated patients. Responses were evident by week 8.

More stringent measures also favored active treatment. About 35% to 36% of patients receiving 15 mg and 46% to 47% receiving 30 mg achieved SALT ≤10 (90% or greater scalp hair coverage), versus approximately 1% of placebo recipients. Complete scalp hair regrowth (SALT 0) occurred in 13% to 14% of patients receiving 15 mg and 20% to 23% receiving 30 mg, while essentially no placebo-treated patients reached this outcome.

Benefits extended beyond the scalp. Approximately 41% to 62% of treated patients achieved major eyebrow improvement and 43% to 61% achieved major eyelash improvement, compared with roughly 1% to 6% of those receiving placebo. Patients also reported meaningful gains in quality of life and disease perception.

Serious adverse events were uncommon, occurring in 1.6% of patients receiving 15 mg and 2.3% receiving 30 mg, versus 0.4% with placebo. The most common adverse events were upper respiratory tract infection, acne, elevated creatine phosphokinase, and nasopharyngitis. No new safety signals were identified.

As the authors noted, “complete scalp hair regrowth (SALT score of 0) is a meaningful and aspirational goal” for patients with alopecia areata.

Source: Mostaghimi A, et al. (2026 Aug 12) JAMA Dermatol. Upadacitinib for Severe Alopecia Areata in Adults and Adolescents: Two Phase 3 UP-AA Randomized Clinical Trials