Upadacitinib Improves Scalp Hair Coverage in Phase 3 UP-AA Trial for Alopecia Areata

AbbVie has announced positive topline results from the first of 2 pivotal studies of the phase 3 UP-AA clinical program evaluating the safety and efficacy of upadacitinib (Rinvoq) 15 mg and 30 mg, once daily in adult and adolescent patients with severe alopecia areata (AA) with a mean baseline SALT score of 83.8, approximately 16% scalp hair coverage.1

According to a July 30, 2025, press release from AbbVie, in Study 2, both doses of upadacitinib achieved the primary endpoint, with 44.6% and 54.3% of patients treated with upadacitinib 15 mg and 30 mg, respectively, reaching 80% or more scalp hair coverage (SALT score ≤ 20) at week 24, compared with 3.4% of patients receiving placebo (P <.001). The Company additionally indicated results from the parallel replicate study (Study 1) of the phase 3 UP-AA clinical program are expected in the third quarter of 2025.1

"The sudden and often unpredictable hair loss people living with AA experience can profoundly impact their self-esteem and mental well-being," Arash Mostaghimi, MD, MPA, MPH, associate professor of dermatology and vice chair of clinical trials and innovation at Brigham & Women's Hospital, Harvard Medical School, said in a statement.1 "There is a pressing need for more treatments that help enable regrowth of scalp and non-scalp hair. I am encouraged by these results that demonstrate the potential of upadacitinib to be an important new treatment option."

A JAK inhibitor being studied in several immune-mediated inflammatory diseases, upadacitinib is currently approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, ankylosing spondylitis, Crohn’s disease, non-radiographic axial spondyloarthritis, and most recently, giant cell arteritis. It is also in phase 3 development for AA, hidradenitis suppurativa, Takayasu arteritis, systemic lupus erythematosus and vitiligo.1,2

UP-AA M23-716 was conducted as a single protocol including 2 replicate pivotal studies, Study 1 and Study 2, with randomization, investigative sites, data collection, analysis and reporting independent for each study. The phase 3 randomized, placebo-controlled, double-blind studies evaluate efficacy and safety of upadacitinib in adult and adolescent patients with severe AA.1

In Study 1 and Study 2 Period A, participants are randomized to 1 of 3 groups to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 24 weeks. In Study 1 and Study 2 Period B, participants originally randomized to upadacitinib dose groups in Period A continue their same treatment in Period B for 28 weeks, while participants originally randomized to placebo in Period A either remain on placebo in Period B or are randomized in 1 of 2 groups based on their SALT score at week 24.1

In total, Study 1 and Study 2 Periods A and B span 52 weeks. Participants who complete Study 1 or Study 2 can join Study 3 and may be rerandomized to receive 1 of 2 doses of upadacitinib for up to 108 weeks. The 2 trials randomized 1399 participants with severe AA ages 12-64 across 248 sites worldwide.1

Results showed 36.0% and 47.1% of patients treated with upadacitinib 15 mg and 30 mg, respectively, reached ≥ 90% scalp hair coverage (SALT ≤ 10) compared with 1.4% of patients receiving placebo at week 24 (P <.001). Additional key secondary endpoints that were met included the percentage of participants with improvements in eyebrows and eyelashes as well as the percentage of subjects with complete scalp hair coverage (SALT = 0) with both doses of upadacitinib at week 24.1

The safety profile of both doses of upadacitinib in the 24-week, placebo-controlled period (Period A) was generally consistent with that observed in approved indications. Treatment-emergent serious adverse events occurred in 1.4% and 2.8% of patients in the upadacitinib 15 mg and 30 mg groups, respectively, and none in the placebo group.1

Additionally, discontinuations due to treatment-emergent adverse events (TEAEs) occurred in 0.7% and 1.4% of participants in the upadacitinib 15 mg and 30 mg groups, respectively, and none in the placebo group, the most common being acne, nasopharyngitis and upper respiratory tract infection. Serious infections were reported infrequently with 0.7% in the upadacitinib 15 mg group and 1.0% in the upadacitinib 30 mg group, and none in the placebo group. While no adjudicated MACE, malignancies, or deaths were reported, a single adjudicated venous thromboembolism was reported in the upadacitinib 15 mg group in a patient with multiple risk factors.1

"Often misunderstood as a cosmetic issue, AA is a systemic immune-mediated disease that can cause total hair loss, involving the scalp, eyebrows and eyelashes. People living with AA may face difficulties in managing their disease, which can significantly affect their quality of life," said Kori Wallace, MD, PhD, vice president, global head of immunology clinical development, AbbVie.1 "UP-AA is the first pivotal program to have ranked and met the rigorous standard of SALT=0, indicating complete scalp hair regrowth. These data underscore AbbVie's commitment to advancing novel treatments that have the potential to improve the lives of individuals with immune-mediated diseases."

References

1. AbbVie. AbbVie Announces Positive Topline Results from Phase 3 UP-AA Trial Evaluating Upadacitinib (RINVOQ®) for Alopecia Areata. July 30, 2025. Accessed July 30, 2025. https://news.abbvie.com/2025-07-30-AbbVie-Announces-Positive-Topline-Results-from-Phase-3-UP-AA-Trial-Evaluating-Upadacitinib-RINVOQ-R-for-Alopecia-Areata

2. Johnson V. FDA Approves Upadacitinib, Expanding Treatment for Adults With Giant Cell Arteritis. HCPLive. April 29, 2025. Accessed July 30, 2025. https://www.hcplive.com/view/fda-approves-upadacitinib-expanding-treatment-for-adults-with-giant-cell-arthritis