TOPLINE

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.

METHODOLOGY

• Researchers conducted two parallel phase 3 randomized 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 years to less than 64 years with severe AA.
• A total of 1399 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 individuals, 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.

TAKEAWAY

• 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 8 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 PRACTICE

“In these two parallel phase 3 replicate randomized 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 of the study wrote. These results, they added, “suggest that upadacitinib may be an effective therapeutic option for adults and adolescents with severe AA.”

SOURCE

The study was led by Arash Mostaghimi, MD, MPA, MPH, Brigham and Women’s Hospital, Boston. It was published online on August 12 in JAMA Dermatology.

LIMITATIONS

The study excluded patients with a current AA episode duration exceeding 8 years, preadolescent children, and adults older than 64 years, limiting generalizability. Additionally, the study population was predominantly White.

DISCLOSURES

The study was funded by AbbVie. Mostaghimi and several other authors disclosed receiving personal fees, nonfinancial support, speaker or consulting fees, research grants, and investigator fees from AbbVie and various other drug companies, including Pfizer, Digital Diagnostics, Eli Lilly and Company, Boehringer Ingelheim, and Indomo. Authors also reported holding a patent, equity ownership, and being a coinventor with AbbVie. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.