Q&A: Upadacitinib's Safety Profile and Role in Severe Alopecia Areata Care

Upadacitinib's safety profile in patients with severe alopecia areata mirrors what clinicians already see across its other approved indications, including psoriatic arthritis (PsA), Crohn's disease, and atopic dermatitis. AbbVie submitted a supplemental new drug application to the US Food and Drug Administration (FDA) on April 28, 2026, seeking approval for adults and adolescents aged 12 years and older with severe disease.¹

Charles Lynde, MD, FRCPC, medical director of the Lynde Institute for Dermatology & Lynderm Research in Markham, Ontario, Canada, co-authored the phase 3 findings supporting the application. The UP-AA1 and UP-AA2 trials, assessing once-daily upadacitinib 15 mg and 30 mg against placebo in 1399 adults and adolescents with severe alopecia areata over 24 weeks,² suggest safety findings were consistent with upadacitinib's established profile in other autoimmune conditions, with no new safety signals identified.¹ Reported events included upper respiratory tract infections, acne, herpes simplex reactivation, and herpes zoster.

Approval down to age 12 would distinguish upadacitinib from JAK inhibitors currently limited to older adolescents or adults. Clinicians can mitigate herpes zoster risk with recombinant zoster vaccination before or during treatment. If cleared, upadacitinib would become the fourth systemic option approved for severe alopecia areata in the US, following baricitinib, ritlecitinib, and deuruxolitinib.²

In the following Q&A interview segment, Lynde discusses the safety profile observed in the UP-AA trials and how the data may reshape his treatment algorithm for severe alopecia areata:

HCPLive: What are your thoughts on the safety data for upadacitinib in this population?

Lynde: This is a drug that's widely used. These JAK inhibitors are used for people with Crohn's disease, psoriatic arthritis, and atopic dermatitis, and we're now finding this is a pathway that many autoimmune diseases can be made better by. The side effect profile is pretty well known: some people get acne, some get a little more upper respiratory tract infections, and if you get cold sores, they can reactivate a little more frequently. We know people can get herpes zoster, shingles, and even at a younger age.

Normally in the population you get shingles when you're 65 or 70 years old, but in this case, people who are 30 years old might develop it. That can be mitigated by getting them vaccinated with Shingrix, which can usually prevent it, or if it doesn't completely prevent it, they're at least covered so it isn't as bad if they get it. The side effect profile is the one seen in other conditions with autoimmune diseases, there were no new signals here, and these side effects occur in a smaller number of patients. People want their hair back, and they're willing to put up with the potential side effects.

HCPLive: How does this new data change where upadacitinib sits in your treatment algorithm for severe disease?

Lynde: This is another JAK inhibitor, and luckily we have several that can be useful. What's beneficial with upadacitinib is it goes down to age 12, while some of the other JAKs with approval only go down to age 18, though they're doing further trials and will likely get subsequent approval for a younger age. Think about it: you're in high school, you're 14 years old, and you lose all your hair. It's hard to go to school, and you can become very anxious, depressed, and everything else, so having a drug that's on-license, that you can get drug coverage for, is extremely important. The other thing is this drug may be working a little earlier than some of the other JAK inhibitors, and may also give a greater number of people who respond to it.

Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. AbbVie. AbbVie submits application to FDA for upadacitinib (Rinvoq) for adults and adolescents with severe alopecia areata. News release. Published April 28, 2026. Accessed August 24, 2026. https://news.abbvie.com/2026-04-28-AbbVie-Submits-Application-to-FDA-for-Upadacitinib-RINVOQ-R-for-Adults-and-Adolescents-with-Severe-Alopecia-Areata.

2. Mostaghimi A, Gooderham MJ, Lynde C, et al. Upadacitinib for severe alopecia areata in adults and adolescents: two phase 3 UP-AA randomized clinical trials. JAMA Dermatol. Published online 2026. doi:10.1001/jamadermatol.2026.2853.