Q&A: Translating UP-AA Trial Data Into Real-World Alopecia Areata Outcomes

Severe alopecia areata, defined by a Severity of Alopecia Tool (SALT) score of 50 or greater, has left clinicians with few systemic options for adults and adolescents with extensive or total scalp hair loss. Charles Lynde, MD, FRCPC, medical director of the Lynde Institute for Dermatology & Lynderm Research in Markham, Ontario, Canada, co-authored new phase 3 data addressing this gap.

UP-AA1 and UP-AA2, 2 replicate phase 3 randomized trials published in JAMA Dermatology, assigned 1399 adults and adolescents with severe disease to once-daily upadacitinib 15 mg, 30 mg, or placebo for 24 weeks.¹ Participants averaged more than a decade of disease duration, and roughly half entered with SALT scores of 95 or higher, indicating near-total scalp hair loss.¹ The trials included 118 adolescents aged 12 - 17 years, broadening the evidence base beyond currently available adolescent options.²

At Week 24, 45.2% and 55.0% of UP-AA1 patients on the 15-mg and 30-mg doses, respectively, reached the primary endpoint of SALT score ≤20 versus 1.5% on placebo (P<.001).¹ UP-AA2 showed comparable results, with 44.6% and 54.3% reaching the endpoint versus 3.4% on placebo, and separation from placebo emerged by Week 8 in both trials.¹ Complete regrowth, defined as SALT 0, occurred in up to 22.5% of treated patients.¹

Achieving SALT score ≤20 corresponds to roughly 80% scalp coverage, a threshold clinicians associate with reduced reliance on wigs and greater tolerance of residual patches. Gains extended beyond the scalp as well, with improvements in eyebrow and eyelash regrowth alongside quality-of-life measures.¹ Below, Lynde discusses the trial population, the clinical significance of the primary endpoint, and why regrowth beyond the scalp matters for patients.

HCPLive: What made this severe alopecia areata population difficult to treat, and how did the UP-AA trial design address that?

Lynde: Alopecia areata can present as small localized areas of hair loss, but in this trial we were looking at people with very severe disease. To get into the trial, you had to have a SALT score, a measure of the amount of hair loss, greater than 50, which translates to 50% loss of all your hair. If you and I look at each other, we're both lucky to have all our hair, but people with 50% loss can't hide it, and many patients in the trial had a SALT score of 100, meaning they had completely lost all their hair.

These are severe, or very severe, patients with alopecia areata. Luckily, there have been a number of newer drugs, mostly JAK inhibitors, found to be useful for this condition, taking people who had lost all their hair for seven or eight years and getting it back again. It's quite amazing.

HCPLive: Clinically, what does hitting 80% scalp coverage by Week 24 mean for a patient in your chair?

Lynde: For people getting a complete response, that's a different bar. Complete response means going from SALT 100 to SALT 0 or SALT 10. Some people got down to SALT 20, meaning they still had 20% loss in their scalp, but at that level, you can usually comb over and find ways to make sure other people don't notice it, so you don't have to wear a wig. When you have SALT 100, everybody notices, and you usually have to wear a wig if you want to hide it.

HCPLive: Why does it matter that eyebrow and eyelash regrowth and quality-of-life scores improved alongside scalp coverage?

Lynde: People want to feel normal again once treatment is over. If you got all your hair back on your scalp but you're missing your eyebrows, you look a little funny. Missing your eyebrows and eyelashes might seem like nothing, but they protect your eyes. Without them, dirt, pollen, and bacteria in the air get into your eyes, so you're getting conjunctivitis all the time. People also miss nose hair in this condition, which acts as a filter to protect your lungs from upper respiratory tract infections, so you want regrowth on the scalp and the face at the same time.

Interestingly, some patients I've had with this and other drugs like it get their eyelashes and eyebrows back, and if they're a guy who doesn't get all their scalp hair back, they're extremely happy because they can shave their head and still look normal because of the eyebrows and eyelashes.

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

References

1. 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.

2. 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