New data on upadacitinib for vitiligo were presented at an updated data session at the 2024 American Academy of Dermatology Annual Meeting in San Diego, California. In a phase 2 trial evaluating the efficacy and safety of upadacitinib in adults with non-segmental vitiligo (NSV), 185 patients (68% with baseline total vitiligo area score index (T-VASI) >10, active (71% with vitiligo) were randomly assigned to: Upadacitinib (UPA) 6mg (n=49), 11mg (n=47), 22mg (n=43), or placebo (n=43).
From Weeks 24 to 52, patients treated with UPA6 (n=38), UPA11 (n=38), and UPA 22 (n=39) continued treatment, while placebo patients received preassigned doses. The patient was switched to upadacitinib PBO-UPA11. [n=19]PBO-UPA22 [n=21]).
The study authors found that skin repigmentation, as measured by facial (F)-VASI and T-VASI, occurred from week 0 to week 24 in all patients treated with upadacitinib, and the primary endpoint was I found that I met and lasted until week 52 without a plateau, achieved. 37%/29% (n=14) of UPA6, 63%/51% (n=24) of UPA11, 38%/26% (n=11) of UPA22, and 32%/29% of T-VASI50, respectively. 25% (n=12), 40%/32% (n=15), and 41%/28% (n=12).
Regarding positive perceptions, 77% to 90% of patients treated with upadacitinib reported that their vitiligo was “much better” or “slightly better” at week 52. The UPA22 group had higher rates of discontinuation and treatment-related serious adverse events.
“Upadacitinib monotherapy was well tolerated, with no new safety signals, and demonstrated clinically meaningful repigmentation of extensive vitiligo after 52 weeks, making it a new and effective systemic treatment for NSV.” '', the authors concluded.
Interviewed by study author Iltefat Hamzabi, MD, FAAD. Dermatology Times We discussed the latest data and shared some of the key highlights that dermatologists should know.
transcript
Iltefat Hamzavi, Maryland: My name is Iltefat Hamzavi. I'm at the Henry Ford Hospital Multicultural Dermatology Center. I am also a member of Hamzabi Dermatology and Dermatology Specialists in the Southeast Detroit area of Michigan.
Dermatology Times: Could you provide a brief background on the data you are presenting at AAD on upadacitinib for vitiligo?
Hamzavi: As you know, vitiligo is an autoimmune disease that tends to cause disfiguring white spots on the face, hands, and body. And there are two variants. There are nonsegmental forms that affect multiple parts of the body, and segmental forms that affect only half of the body. These are different immune disease conditions. As a result, non-segmental vitiligo, which accounts for the majority of vitiligo patients, is the basis for treatment that is different from that for partial vitiligo. The above is a non-segment consideration. Vitiligo is this highly undertreated and disfiguring condition. The 52-week period was a Phase 2b multicenter study, and the primary endpoint was a scoring system called VASI. And it was disassembled into facial VASI. and whole body VASI. In this study, patients were given the medication for one year, and the study involved approximately 185 patients, divided into a placebo, a 6-milligram dose, an 11-milligram dose, a 22-milligram dose, and finally a placebo. did. Then, at approximately 28 weeks, patients can be switched to the active treatment arm, with those on the placebo able to receive the active drug, and then those receiving the active drug receive an additional 6 months. It will be extended.
Dermatology Times: What are the most important takeaways your colleagues should know from this data?
Hamzavi: Active drugs began to show improvement at 6 months. Improvements continued to be seen at 52 weeks. 52 weeks of data was the best data. The face fares better than other parts of the body, and this is true for most patients treated for non-segmental vitiligo. Higher doses, the highest dose of 22 milligrams, did not produce the best effects. Therefore, even this low dose did not produce optimal effects. The one that worked best was a Goldilocks moment at an 11-milligram dose. On his VASI of the face, the peak response to 11 milligrams was 63%, compared to about 51% for the placebo. Therefore, all treatment groups are superior to placebo.
However, the best overall response was around 11 milligrams, so the 11 milligram dose may be more effective. And for total VASI, below the neck area, 6 6 milligrams, 11 and 22, 30%, 40%, 41%. and placebo responses were approximately 29%, 51%, and 26%, respectively. The final outcome measure was patient impressions. As many people may understand, and perhaps you may not, vitiligo is a disease of well-being. When a disease disfigures one's appearance, it's not the pain of the disease, but social acceptance, self-confidence, and the highest incidence of depression in the field. And many patients have evidence of depression in PHQ, 2 and 9. So we measured patient impressions and found that 77% to 90% of the patients in the study reported that their vitiligo was much better or a little better at 52 weeks, so 77% felt much better. This means that 90% of the results are slightly better. And finally, there were no new safety signals. JAK inhibitors have safety issues, but there are no new safety signs.
Dermatology Times: In your opinion, what are the real-world applications of upadacitinib for vitiligo?
Hamzavi: When there is a serious disfiguring condition and there is an emergency, one of the most important things to do is to counsel the patient. And this drug takes time to take effect. Also, how safe is the drug when used long-term? So how do you encourage patients to continue using it? That is, if they see an initial response at 6 months? The fact that we're seeing better responses at 52 weeks. And if it follows what we already know from other therapeutic interventions such as topical therapy and phototherapy, treatment response will continue to improve beyond 52 weeks. And we also want to make sure that this drug is safe. And since this drug is in the JAK category, the fact that there are no new safety signs means that there are safety issues and no new safety signs have been identified, so the Phase 3 trial is It gives you some confidence that it's valid. Although dosing takes time, there is some confidence that this appears to have the same safety profile as other therapeutic indications, at least initially. And hopefully we can find a way to restore the pigment faster. However, the fact that patients noticed changes was a positive finding. Very exciting. And the last part is the decline, where at higher doses there is an improvement and then there is a plateau. Well, you don't want to administer drugs at high rates unless you have to. And it must be justified. Apparently, the right amount of medicine has been found. There are thus many interesting discoveries that will help patients in the very near future.
[Transcript lightly edited for space and clarity.]
reference
Passeron T, Ezzedine K, Hamzavi I et al. Efficacy and safety after 52 weeks of once-daily administration of upadacitinib in adults with extensive non-segmental vitiligo (NSV): a phase 2, multicenter, randomized study. Final results of a double-blind, placebo-controlled, dose-ranging study. Presentation location: 2024 American Academy of Dermatology Annual Meeting. From March 8th to 12th, 2024. San Diego, California.