Upadacitinib may improve scalp hair regrowth in adults and adolescents with severe alopecia areatacompared with placebo.
In 2 parallel, global, double-blind, placebo-controlled phase 3 randomized clinical trials, UP-AA1 and UP-AA2, researchers enrolled 1,399 patients with severe alopecia areata, including 118 adolescents. Eligible patients were aged 12 to under 64 years and had a Severity of Alopecia Tool (SALT) score of at least 50, indicating at least 50% scalp hair loss. Patients were randomly assigned 2:2:1 to receive once-daily oral upadacitinib 15 or 30 mg or placebo for 24 weeks. The mean baseline SALT score was 83.9.
The primary endpoint was achievement of a SALT score of 20 or less at week 24, corresponding to no more than 20% scalp hair loss. Key secondary endpoints included achievement of SALT scores of 10 or less and 0. The researchers assessed eyebrow and eyelash regrowth, early treatment response, patient-reported disease improvement, and health-related quality of life.
Both trials met their primary endpoint. In UP-AA1, 45% of patients receiving 15-mg upadacitinib and 55% receiving 30-mg upadacitinib achieved a SALT score of 20 or less at week 24 vs. 2% receiving placebo. Corresponding response rates in UP-AA2 were 45%, 54%, and 3%, respectively. Adjusted differences vs. placebo ranged from 41 to 44 and 51 to 54 percentage points for the 15-and 30-mg doses, respectively.
More extensive scalp hair regrowth favored upadacitinib. Across the trials, 35% to 36% of patients receiving 15 mg and 46% to 47% receiving 30 mg achieved a SALT score of 10 or less at week 24 vs. about 1% receiving placebo. Complete scalp hair regrowth occurred in 13% to 14% of patients receiving 15 mg and 20% to 23% receiving 30 mg vs. 0% to 1% receiving placebo. Statistically significant differences in the primary endpoint between both upadacitinib doses and placebo were observed by week 8.
Treatment benefits extended to eyebrow and eyelash regrowth. Among patients with substantial eyebrow hair loss at baseline, 41% to 42% receiving 15 mg and 59% to 62% receiving 30 mg achieved clinically meaningful eyebrow improvements at week 24 vs. 1% to 3% receiving placebo. Corresponding eyelash response rates were 43% to 44% and 59% to 61%, respectively, vs. 4% to 6% receiving placebo.
At week 24, 65% to 68% of patients receiving 15 mg and about 75% receiving 30 mg reported that their alopecia areata was moderately or much better vs. 7% to 8% receiving placebo. Improvements were also observed in disease-related symptoms, interference with daily activities, and emotional and functional quality-of-life measures.
Although the 30-mg dose consistently produced greater response rates than the 15-mg dose for most endpoints, the researchers did not conduct formal statistical comparisons. Adolescent patients demonstrated greater treatment effects than the overall study population, although just 118 adolescents were enrolled.
The safety profile of upadacitinib was consistent with that observed in its approved indications, with no new safety signals identified during the 24-week treatment period. Treatment-emergent adverse events occurred in 63% of patients receiving 15 mg, 67% receiving 30 mg, and 57% receiving placebo. Common events included acne, nasopharyngitis, upper respiratory tract infections, and elevated blood creatine phosphokinase. Serious adverse events occurred in 2% of patients receiving either upadacitinib dose and less than 1% receiving placebo. No mortality was reported.
The study had several limitations, including the 24-week placebo-controlled observation period, which restricted conclusions about longer-term efficacy and safety. Patients with a current alopecia areata episode lasting more than 8 yearsandpatients outside the study's age range were excluded, limiting generalizability. More than half of participants were White, and the adolescent subgroup was relatively small. Longer-term follow-up is needed to evaluate the durability of treatment responses and the safety profile over extended treatment periods.
“These findings suggest that upadacitinib may be an effective therapeutic option for adults and adolescents with severe [alopecia areata],” wrote lead study author Arash Mostaghimi, MD, of Brigham and Women’s Hospital, and colleagues.
Full disclosures of the study authors can be found in the study.
Source: JAMA Dermatology
