Upadacitinib Shows Strong Efficacy in Second Pivotal Phase 3 Study for Severe Alopecia Areata

Building on its momentum in alopecia areata (AA) research, AbbVie recently announced new positive top-line results from the second pivotal study in its phase 3 UP-AA clinical program evaluating upadacitinib (Rinvoq; AbbVie) for severe AA.¹

In the second study of the UP-AA program (NCT06012240),² both the 15 mg and 30 mg once-daily dose cohorts receiving treatment with upadacitinib achieved the primary end point, with 44.6% and 54.3% of patients, respectively, achieving greater than or equal to 80% scalp hair coverage (Severity of Alopecia Tool [SALT] ≤ 20) by week 24. These responses were statistically superior to placebo (3.4%; P < .001), confirming upadacitinib’s potential as a targeted oral therapy for severe AA.

Upadacitinib outperformed placebo across all ranked secondary end points, including more stringent thresholds of hair regrowth (SALT ≤ 10 and SALT = 0) and regrowth of eyebrows and eyelashes.

“The UP-AA phase 3 findings highlight upadacitinib’s potential as a best-in-class, once-daily, JAK1 selective inhibitor for alopecia areata, delivering the highest levels of scalp hair regrowth reported to date in a pivotal trial, with many patients reaching near-complete or full coverage within 24 weeks,” Christopher Bunick, MD, PhD, associate professor of dermatology at Yale School of Medicine in New Haven, Connecticut, and editor in chief of Dermatology Times, said in a statement. “These results set a new benchmark for efficacy in alopecia areata and mark a significant advancement in what can be achieved with targeted inhibition for this challenging disease.”

Efficacy Across Key Domains

Upadacitinib demonstrated clear dose-dependent efficacy. By week 24, 36.0% (15 mg) and 47.1% (30 mg) of patients reached greater than or equal to 90% scalp coverage (SALT ≤ 10), and a meaningful proportion achieved complete regrowth (SALT = 0). Both doses yielded significant improvement in facial hair parameters, including eyebrow and eyelash restoration.

“Alopecia areata, when severe and resistant to traditional treatments, is disfiguring and debilitating. This is a breakthrough moment in AA treatment,” said Amy Spizuoco, DO, a board certified dermatologist and dermatopathologist at True Dermatology, associate clinical instructor in the Department of Dermatology at The Icahn School of Medicine at Mount Sinai in New York, and a Dermatology Times editorial advisory board member. “Upadacitinib’s high rates of substantial and even complete hair regrowth, plus its favorable safety profile, mark a new standard for therapeutic efficacy in a challenging autoimmune condition that significantly impacts mental health and self-esteem. I’ve personally seen the efficacy in my patients, and am eager for its FDA approval.”

Safety Profile

Upadacitinib’s safety in this patient population with AA mirrored findings from its use in other approved indications, such as atopic dermatitis and rheumatoid arthritis. Serious treatment-emergent adverse events (TEAEs) were infrequent, with 1.4% (15 mg) and 2.8% (30 mg) of patients reporting serious TEAEs. Discontinuations due to TEAEs were low (≤ 1.4% across groups), and the most commonly reported AEs included acne, nasopharyngitis, and upper respiratory tract infections.

Although upadacitinib is not yet approved for AA, this safety profile aligns with findings from a recent scoping review of 24 studies (n = 64), which concluded that the therapeutic was generally well tolerated, with only mild, transient AEs such as acneiform eruptions, transient cytopenias, and elevated creatine phosphokinase levels.³

Regulatory Path

“UP-AA is the first pivotal program to have ranked and met the rigorous standard of a SALT [score of] 0, indicating complete scalp hair regrowth,” Kori Wallace, MD, PhD, vice president and global head of immunology clinical development at AbbVie, said in a news release.¹ “These data underscore AbbVie’s commitment to advancing novel treatments that have the potential to improve the lives of individuals with immune-mediated diseases.”

The full UP-AA program includes 2 identically designed global trials—Study 1 and Study 2—that are both double-blind, placebo-controlled studies randomizing 1399 participants aged 12 to 64 years with severe AA (mean SALT 83.8). Study 1 results are expected in the third quarter of 2025.

Participants completing either pivotal trial may continue in a long-term extension study (Study 3) for up to 108 weeks to assess sustained response and long-term safety. These data will be critical to support potential regulatory submissions.

“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,” Wallace said.

References

1. AbbVie announces positive topline results from phase 3 UP-AA trial evaluating upadacitinib (RINVOQ) for alopecia areata. News release. AbbVie. 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. A study to evaluate the safety and effectiveness of upadacitinib tablets in adult and adolescent participants with severe alopecia areata (Up-AA). ClinicalTrials.gov. Updated July 16, 2025. Accessed July 30, 2025. https://clinicaltrials.gov/study/NCT06012240

3. Stirrat T, Thakker S, Bejugam D, Goh C, Lipner SR. Upadacitinib for alopecia: current evidence and clinical insights. Skin Appendage Disord. 2025;11(4):320-334. doi:10.1159/000544868