Oral Upadacitinib Significantly Reduces Facial, Total Nonsegmental Vitiligo Through 52 Weeks

Once-daily upadacitinib was associated with clinically meaningful reductions in facial and total vitiligo severity compared to placebo among treated adults with extensive non-segmental vitiligo (NSV), according to phase 2b data presented at the American Academy of Dermatology (AAD) 2024 Annual Meeting.¹

In late-breaking data presented at AAD 2024 this weekend, AbbVie’s oral selective JAK inhibitor was associated with a 20.7% change in total vitiligo per Vitiligo Area Severity Index (T-VASI) at 24 weeks when administered at a 22 mg daily dose, versus a 6.4% change among the placebo arm. Investigators additionally reported that 39.5% (n = 17) patients treated with 22 mg upadacitinib achieved ≥50% facial vitiligo improvement per F-VASI in the same time period.

By week 52 of the clinical trial, the 22 mg dose arm reported a mean percentage change of 60.8% in F-VASI, and 44.4% in T-VASI. Among the 11 mg dose arm, such changes were 64.9% and 44.7%, respectively, at week 52.

Regarding safety and tolerability, the investigators reported no new safety signals associated with upadacitinib. Overall, the findings demonstrated a dose-dependent response from upadacitinib in patients with NSV, as the 11 mg and 22 mg doses were more efficacious than the 6 mg dose and placebo. Investigators now intend to evaluate 15 mg upadacitinib in a phase 3 trial based on exposure-response modeling data these results.

In an interview with HCPLive during AAD 2024, primary investigator Thierry Passeron, MD, PhD, of Cote d’Azur University and the department of dermatology at the University Hospital of Nice in France, discussed the potential utility of upadacitinib—already an established therapy for atopic dermatitis—in non-segmental vitiligo.² Its function as a JAK-1 pathway inhibitor gives reason to consider its benefit in addressing the autoimmune characteristics of vitiligo, similar to ruxolitinib cream.

“Here, it’s an oral treatment, so it’s mostly for extensive and/or active vitiligo,” Passeron said. “The high need is for nonsegmental vitiligo. Ruxolitinib cream has already provided some good, encouraging results for patients with localized vitiligo. But for patients with widespread vitiligo you cannot apply a cream twice a day for many months.”

Upadacitinib may serve to benefit as a systemic approach to patients with >5% body surface involvement with vitiligo, Passeron explained. A secondary benefit would be in helping to address active forms of vitiligo that which can result in “rapid depigmenting” all over the body.

“This is why there is a clear need of systemic treatment for this kind of vitiligo,” he said.

Regarding the phase 2b findings presented at AAD 2024, Passeron stressed that the treatment response to 11 mg and 22 mg upadacitinib had not plateaued at 52 weeks—meaning there’s opportunity for even greater efficacy per T-VASI and F-VASI going beyond a year with the daily oral dose.¹

Approximately two-thirds of the trial participants were reported to have active vitiligo at baseline, Passeron said. Though the data need to be confirmed, upadacitnib appeared to be potentially more effective for this particular group.

“So, if the treatment confirms that it's not only able to repigment but also to halt the disease progression, that will be a great hope for the patient to maintain,” he said.

References

1. ^{Passeron T, Ezzedine K, Hamzavi I, van Geel N, et al. Efficacy and Safety After 52 Weeks of Once-Daily Upadacitinib in Adults With Extensive Non-Segmental Vitiligo: Final Results From a Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study. Paper presented at: American Academy of Dermatology (AAD) 2024 Annual Meeting. March 8 – 12, 2024. San Diego, CA.}
2. ^{Smith T. Phase 3 Results on Upadacitinib for Atopic Dermatitis with Jonathan Silverberg, MD, PhD. HCPLive. Published March 8, 2024. https://www.hcplive.com/view/phase-3-results-on-upadacitinib-for-atopic-dermatitis-with-jonathan-silverberg-md-phd}