UP-AA: Upadacitinib Attains Primary Endpoint in New Alopecia Areata Data

Two phase 3 replicate randomized clinical trials, UP-AA1 and UP-AA2, found upadacitinib (Rinvoq) significantly outperformed placebo in achieving a Severity of Alopecia Tool (SALT) score of 20 or less at Week 24 in adults and adolescents with severe alopecia areata, meeting the primary efficacy end point at both the 15-mg and 30-mg doses.¹

Currently only baricitinib, ritlecitinib, and deuruxolitinib are approved oral JAK inhibitors for severe alopecia areata, and only ritlecitinib carries an adolescent indication, leaving a gap for additional systemic options.¹ Prior trials of these agents left many patients short of the SALT ≤20 threshold, with response rates topping out around 35% across treatment groups.²

UP-AA1 and UP-AA2 enrolled 1399 patients across 25 and 28 countries, respectively, including 118 adolescents ages 12 to 17 years, making the program one of the largest phase 3 evaluations of a JAK inhibitor in this population.¹

Upadacitinib Efficacy in UP-AA1 and UP-AA2

UP-AA1 and UP-AA2 are global, randomized, double-blind, placebo-controlled phase 3 trials conducted at 112 centers in 25 countries and 125 centers in 28 countries, respectively, from October 2023 to July 2025.¹ Eligible patients were adolescents (age 12-17 years, weight ≥30 kg) or adults (age 18 to <64 years) with a SALT score of 50 or greater and no spontaneous scalp regrowth in the prior 6 months.¹ Patients were randomized 2:2:1 to once-daily 15-mg upadacitinib, 30-mg upadacitinib, or placebo for a 24-week double-blind period, followed by a 28-week blinded extension.¹

Baseline mean SALT score across both trials was 83.9 (SD, 18.9), reflecting a population with extensive scalp hair loss.¹ Both trials met the primary end point: SALT score ≤20 at Week 24 was attained by 45.2% (122/270) of patients on 15-mg upadacitinib and 55.0% (149/271) on 30-mg upadacitinib in UP-AA1, compared with 1.5% (2/135) on placebo (P <.001 for both doses).¹ In UP-AA2, response rates were 44.6% (129/289) with 15 mg and 54.3% (157/289) with 30 mg, versus 3.4% (5/145) with placebo (P <.001).¹

Separation from placebo emerged as early as Week 8 for both doses in both trials.¹

Upadacitinib Secondary Endpoints and Safety Profile

Both doses also outperformed placebo on more stringent efficacy measures. Complete scalp hair regrowth, defined as SALT score of 0, was reached by 20.3% of patients on 30-mg upadacitinib in UP-AA1 and 22.5% in UP-AA2, compared with 0% and 0.7% on placebo, respectively (P <.001).¹ Clinician-reported outcomes for eyebrow and eyelash hair loss improved significantly with both doses versus placebo across both trials (P <.001 for all comparisons).¹

Patients on upadacitinib also reported significantly greater improvement in AA-specific quality-of-life measures, including the Alopecia Areata Symptom Impact Scale and Skindex-16 alopecia areata emotions and functioning domains, at Week 24.¹

Treatment-emergent adverse events (TEAEs) were numerically higher with 30-mg upadacitinib than with 15 mg or placebo, occurring in 67.1%, 62.7%, and 57.1% of patients, respectively, in the pooled safety analysis.¹ The most common TEAEs reported in more than 5% of patients in any group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis.¹ Serious adverse events occurred in 2.3% of patients on 30-mg upadacitinib, 1.6% on 15 mg, and 0.4% on placebo, with no deaths reported in either trial.¹

Investigators characterized the safety profile as consistent with upadacitinib's other approved indications, with no new safety signals identified.¹

Upadacitinib is already approved for multiple inflammatory indications, including atopic dermatitis, a condition frequently comorbid with alopecia areata.¹ A third study is underway to evaluate long-term efficacy, safety, and dose adjustment strategies through Week 52 of UP-AA1 and UP-AA2, which will help define upadacitinib's place relative to baricitinib, ritlecitinib, and deuruxolitinib in severe alopecia areata.¹

References

1. Mostaghimi A, Gooderham MJ, Lynde C, et al. Upadacitinib for severe alopecia areata in adults and adolescents: two phase 3 UP-AA randomized clinical trials. JAMA Dermatol. Published online August 12, 2026. doi:10.1001/jamadermatol.2026.2853.

2. King B, Ohyama M, Kwon O, et al; BRAVE-AA Investigators. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386(18):1687-1699. doi:10.1056/NEJMoa2110343.