Treatment with the oral JAK inhibitor upadacitinib appears to lead to substantial hair regrowth in patients with severe alopecia areata, as shown in the two parallel phase III UP-AA1 and UP-AA2 studies.
Over 24 weeks of treatment, around 45 percent of patients who received 15-mg upadacitinib (45.2 percent and 44.6 percent) and 55 percent of those who received the 30-mg dose (55 percent and 54.3 percent) achieved at least 80-percent scalp hair coverage (Severity of Alopecia Tool [SALT] score ≤20) compared with 1.5 percent and 3.4 percent of placebo-treated patients in UP-AA1 and UP-AA2, respectively (p<0.001 for all). [JAMA Dermatol 2026;doi:10.1001/jamadermatol.2026.2853]
“Both doses of upadacitinib also showed superiority to placebo in most multiplicity-controlled secondary endpoints,” reported lead investigator Dr Arash Mostaghimi from Brigham and Women’s Hospital, Boston, Massachusetts, US, and colleagues.
Complete scalp hair regrowth (SALT score 0) occurred in 13 percent to 14 percent of patients in the 15-mg upadacitinib groups and 20 percent to 23 percent of those in the 30-mg groups vs none in the placebo groups (p<0.001 for all). SALT score ≤10 responses were also much higher with upadacitinib, at 35.2 percent to 36 percent in the 15-mg groups and 45.8 percent to 47.1 percent in the 30-mg groups vs 0.7 percent to 1.4 percent in the placebo groups (p<0.001).
Eyebrow and eyelash regrowth was also observed among upadacitinib-treated patients, with eyebrow and eyelash hair loss improving by at least 2 points from baseline on the clinician-reported outcome (ClinRO) measure in 40.6 percent to 43.7 percent of patients in the 15-mg groups and 58.6 percent and 61.8 percent of those in the 30-mg groups as compared with 1.1 percent to 5.6 percent of those in the placebo groups (p<0.001 for all).
In both studies, responses for SALT score ≤20 and ClinRO measures for eyebrow and eyelash were observed as early as week 8 with upadacitinib, Mostaghimi and colleagues noted.
Psychosocial improvements
“Patients treated with upadacitinib met SALT scores of ≤10 and 0—endpoints that demonstrate deeper levels of scalp hair regrowth that are shown to be associated with significant improvements in psychosocial outcomes across multiple measures,” according to the investigators.
Indeed, patients who received upadacitinib in the UP-AA1 and UP-AA2 studies also had significant improvements in patient impression of change as well as in multiple facets of health-related quality of life, they added.
At week 24, more patients in the upadacitinib groups than in the placebo groups rated their treatment outcome as much better or moderately better, based on the Patient Global Impression (PaGIC-AA scores of 1 or 2), at 65 percent to 75 percent vs around 7 percent.
Furthermore, both upadacitinib doses were associated with greater improvements in Alopecia Areata symptom impact scale interference and symptoms subscales, Skindex-16 AA emotions, and functioning domains.
“In a disease often associated with sizable psychosocial and emotional burden, translation of clinical responses (hair regrowth) into meaningful patient-reported improvements becomes imperative to deem a treatment to be efficacious,” Mostaghimi and colleagues said.
Valuable treatment option
“Upadacitinib is currently approved for multiple indications, including atopic dermatitis, which is noted as a comorbidity in patients with alopecia areata. The rapidity and depth of response [seen in the UP-AA1 and UP-AA2 studies] have the potential to position upadacitinib as a valuable treatment option for patients with severe alopecia areata,” according to the investigators.
The finding on complete scalp hair regrowth (SALT score of 0) with upadacitinib has important implications, given that complete scalp hair regrowth is different in gradation from more limited hair restoration and was not assessed as a key ranked endpoint in the primary analyses for the currently approved oral JAK inhibitors, they said.
UP-AA1 and UP-AA2 studies
The two studies included a total of 1,399 adolescents and adults (mean age 36 years, 59 percent female) who had baseline SALT scores of at least 50 (mean 83.9), no spontaneous scalp hair regrowth during the past 6 months, and a current episode of alopecia areata lasting less than 8 years.
The patients were randomly assigned to receive upadacitinib at 15 mg (n=270 in UP-AA1, n=289 in UP-AA2) or 30 mg (n=271 in UP-AA1, n=289 in UP-AA2) or placebo (n=135 in UP-AA1, n=145 in UP-AA2). Treatment was administered orally, once daily during a 24-week placebo-controlled, double-blind period and a 28-week blinded extension treatment period.
No new safety risks
“The safety profile of both doses of upadacitinib through 24 weeks was generally consistent across both studies, similar in adolescents and adults, and consistent with that observed in atopic dermatitis and other approved indications,” the investigators noted. “No new safety risks were observed.”
Treatment-emergent serious adverse events (AEs) occurred in 1.6 percent, 2.3 percent, and 0.4 percent of patients in the pooled 15-mg, 30-mg, and placebo groups, respectively. The most common treatment-emergent AEs were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis.