Researchers in the US have said that upadacitinib, an oral selective JAK inhibitor, significantly improved scalp hair regrowth and quality of life vs placebo in adults and adolescents with severe alopecia areata (AA) in two phase 3 trials, reports Medscape.
The scientists had conducted two parallel phase 3 randomised clinical trials, UP-AA1 and UP-AA2, from October 2023 to July 2025 across 25 and 28 countries, respectively, evaluating upadacitinib in patients aged 12 to 64 with severe AA.
A total of 1 399 patients were randomly assigned in a 2:2:1 ratio to receive once-daily oral upadacitinib 15 mg (270 patients in UP-AA1, 289 in UP-AA2), upadacitinib 30 mg (271 in UP-AA1, 289 in UP-AA2), or a matching placebo (135 in UP-AA1, 145 in UP-AA2) for 24 weeks.
Mean patient age was 34.9 and 36.8 years in UP-AA1 and UP-AA2, respectively; 57.8%-60.2% were women; 55.6%-67.6% were white, 35.2%-24.2% were Asian, and 6.2%-5.4% were black, respectively.
The primary efficacy endpoint was achievement of a Severity of Alopecia Tool (SALT) score ≤ 20 (≤ 20% scalp hair loss) at week 24; secondary endpoints included SALT scores ≤ 10 and 0, improvements in eyebrow and eyelash hair loss, and health-related quality-of-life measures.
Pleasing results
In UP-AA1, 45.2% of patients receiving 15 mg upadacitinib and 55.0% receiving 30 mg achieved a SALT score ≤ 20 at week 24 compared with 1.5% of patients on placebo (P < .001 for both doses); in UP-AA2, 44.6% and 54.3% achieved this endpoint with 15 mg and 30 mg, respectively, vs 3.4% with placebo (P < .001 for both). Responses were observed as early as eight weeks.
Complete scalp hair regrowth (SALT score 0) at week 24 was achieved by 14.1% of patients on 15 mg and 20.3% on 30 mg in UP-AA1 vs 0% on placebo (P < .001), and by 13.1% and 22.5% with 15 mg and 30 mg in UP-AA2 vs 0.7% on placebo (P < .001). SALT score ≤ 10 was achieved by 35.2% and 36% of patients receiving the 15-mg dose and 45.8% and 47.1% of patients receiving the 30-mg dose in the UP-AA1 and UP-AA2 groups, respectively, vs 0.7% and 1.4% in the placebo group (P < .001 for all).
At week 24, both upadacitinib doses led to significant improvements in clinician-reported outcomes for eyebrow and eyelash hair loss and patient-reported quality-of-life measures (P < .001 for all comparisons).
Treatment-emergent adverse events occurred in 62.7% of patients receiving 15 mg upadacitinib and 67.1% receiving 30 mg vs 57.1% on placebo; upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis were most common.
Serious adverse event rates were 1.6% and 2.3%, respectively, in the 15-mg and 30-mg dose groups, and 0.4% for placebo.
“In these two parallel phase 3 replicate randomised clinical trials, the 24-week double-blinded period A of UP-AA1 and UP-AA2 demonstrated the superiority of both 15-mg and 30-mg upadacitinib compared with placebo in adult and adolescent patients with severe AA,” the authors wrote.
These results, they added, “suggest that upadacitinib may be an effective therapeutic option for adults and adolescents with severe AA”.
The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital, Boston, and published online in JAMA Dermatology.
Limitations
The study, funded by AbbVie, excluded patients with a current AA episode duration exceeding eight years, pre-adolescent children, and adults over 64, limiting generalisability. Additionally, the study population was predominantly white.
Study details
Upadacitinib for Severe Alopecia Areata in Adults and Adolescents
Arash Mostaghimi, Melinda Gooderham, Charles Lynde et al.
Published in JAMA Dermatology on 12 August 2026
Abstract
Importance
Alopecia areata (AA) is a chronic, systemic immune-mediated disease characterised by non-scarring hair loss. Many patients do not experience improvements with available treatment options and only ritlecitinib is approved for adolescent patients; therefore, there remains a clear unmet need for additional and improved systemic therapies.
Objective
To evaluate the efficacy and safety of upadacitinib – an oral selective Janus kinase inhibitor – in adult and adolescent patients with severe AA.
Design, Setting, and Participants
This global clinical programme included two parallel phase 3 replicate randomised clinical trials (UP-AA1 and UP-AA2) conducted from October 2023 to July 2025, to evaluate upadacitinib in adolescent and adult patients (age 12 to <64 years old) with severe AA, defined as a Severity of Alopecia Tool (SALT) score of 50 or greater. Both trials included a 24-week placebo-controlled, double-blinded treatment period (period A) and a 28-week blinded extension treatment period (period B). Data were analysed from July 2025 to October 2025.
Interventions
Eligible patients were randomised 2:2:1 to once daily 15- or 30-mg upadacitinib or matching placebo.
Main Outcomes and Measures
Achievement of (multiplicity controlled) SALT score of 20 or less at week 24. Multiplicity-controlled secondary efficacy end points included achievement of improvements in clinician-reported outcomes for eyebrows and eyelashes; achievement of SALT scores of 20 or less at weeks 4, 8, and 12; achievement of SALT score of 10 or less; SALT score 0 at week 24; patients’ global impression of change of AA score of much better or moderately better at weeks 4 and 24; and other AA-specific health-related quality of life measures at week 24.
Results
A total of 1 399 patients were randomised (mean [range] age, 36 [12-64] years; 826 female [59.0%]), 676 patients from the UP-AA1 and 723 patients from the UP-AA2, to either 15-mg upadacitinib (270 and 289 patients, respectively), 30-mg upadacitinib (271 and 289), or placebo (135 and 145). Their mean (SD) SALT score was 83.9 (18.9) at baseline. The proportion of patients who achieved SALT score of 20 or less at week 24 was significantly higher for the 15-mg upadacitinib (122 [45.2%] and 129 [44.6%]) and the 30-mg upadacitinib (149 [55.0%] and 157 [54.3%]) groups, respectively, than for the placebo (2 [1.5%] and 5 [3.4%]) group. The safety profile of both doses was similar in adults and adolescents and consistent with approved indications; no new safety findings were identified. Treatment-emergent adverse events reported by more than 5% of patients in any treatment group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis. Across both studies, treatment-emergent serious adverse events occurred in 9 (1.6%), 13 (2.3%), and 1 (0.4%) of patients receiving 15-mg upadacitinib, 30-mg upadacitinib, or placebo, respectively.
Conclusions and Relevance
In these two parallel phase 3 replicate randomised clinical trials, upadacitinib demonstrated a positive benefit-risk profile in adults and adolescents with severe AA. Upadacitinib may be a potentially effective treatment option for this patient population.
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