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Late-Breaking Data: Upadacitinib for Vitiligo Achieves Skin Repigmentation Through Week 52


Iltefat Hamzavi, MD, reviews late-breaking data at AAD on upadacitinib as monotherapy.

New data on upadacitinib for vitiligo was presented in a late-breaking 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% baseline total vitiligo area scoring index (T-VASI) >10; 71% active vitiligo) were randomized to upadacitinib (UPA) 6mg (n=49), 11mg (n=47), 22mg (n=43), or placebo (n=43).

Through weeks 24 to 52, patients treated with UPA6 (n=38), UPA11 (n=38), and UPA 22 (n=39) continued treatment, while placebo patients switched to a pre-assigned upadacitinib dose PBO-UPA11 [n=19], PBO-UPA22 [n=21]).

The study authors found that skin re-pigmentation as measured by facial (F)-VASI and T-VASI occurred in all upadacitinib-treated patients from week 0 to 24, therefore meeting the primary endpoint, and continued without plateau through week 52 with achievement of F-VASI75 in 37%/29% of UPA6 (n=14), 63%/51% of UPA11 (n=24), 38%/26% of UPA22 (n=11) and achievement of T-VASI50 in 32%/25% (n=12), 40%/32% (n=15), and 41%/28% (n=12), respectively.

Regarding positive perceptions, 77% to 90% of upadacitinib-treated patients reported their vitiligo as "much better" or "a little better" at week 52. Higher rates of discontinuation and serious related treatment-emergent adverse events occurred in UPA22 group.

“Upadacitinib monotherapy was well tolerated with no new safety signals and demonstrated clinically meaningful re-pigmentation of extensive vitiligo after 52 weeks, potentially offering a new and effective systemic treatment for NSV,” concluded the authors.

Study author Iltefat Hamzavi, MD, FAAD, spoke to Dermatology Times about the late-breaking data and shared some of the important highlights for dermatologists to know.


Iltefat Hamzavi, MD: My name is Iltefat Hamzavi. I'm at the Henry Ford Hospital Multicultural Dermatology Center. I'm also part of Hamzavi Dermatology & Dermatology Specialists all in the southeast Michigan Detroit area.

Dermatology Times: Can you please provide a brief background on the data that you're presenting at AAD on upadacitinib for vitiligo?

Hamzavi: As you know, vitiligo is an autoimmune disease, which tends to cause disfiguring white patches on the face, hands, and the body. And there are 2 variants: There's the nonsegmental, which affects multiple parts of the body, and the segmental, which only affects half the body. They're different immunological disease states. So as a result, nonsegmental vitiligo, which is a majority of people with vitiligo, as a different base of treatment than segmental. So, this was a study of nonsegmental. vitiligo for this very undertreated and disfiguring condition. And 52 weeks is a phase 2b multicenter study, and the primary end point was a scoring system called the VASI. And it was broken up into the facial VASI. And then the total body VASI. And so in this study, the patients were given medication for one year, there's about 185 patients in the study, and they were broken up into placebo, 6 milligram dosing, 11 milligram dosing, and 22 milligram dosing, and then there was a placebo arm and then at about 28 weeks, patients were able to flip into an active treatment arm so that the people on placebo could get active drug, and then the people who are getting active drug get extended over another six months.

Dermatology Times: What are the key takeaways that are the most important for your fellow colleagues to know from this data?

Hamzavi: The active drugs started to show improvement at a 6-month point. And it continued to show better improvements at the 52-week point. The 52-week data was the best data. The face did better than the rest of the body, which is the case with most patients who are undergoing treatment for nonsegmental vitiligo. The higher dose, the highest dose, which was 22 milligrams did not do the best. So, this lower dose also did not do the best. It was the Goldilocks moment for the 11 milligrams dosing which had the best response. For the facial VASI, the peak response for the 11 milligrams was 63% response as compared to around 51% placebo response. And so, all treatment arms are better than the placebo.

But the best response overall result was around 11 milligrams, so it seems 11 milligram dosing may be more effective. And then for the total VASI, the area below the neck, 6 six milligram, 11 and 22, 30%, 40%, and 41%. And the placebo response was around 29%, 51%, and 26%, respectively. The last outcome measure was a patient impression, as many people may understand or maybe you don't know, vitiligo is a disease of well-being. When you are disfigured by a condition, it's not the pain of the condition it's the social acceptance, the confidence, the rates of depression are some of the highest in our field. And many patients have a PHQ, 2 and 9 basis of depression. So, we measured patient impressions, and 77% to 90% of people in the study reported that their vitiligo was much better, or a little better at 52 weeks, so 77% much better and 90% a little better. And there were lastly, no new safety signals. JAK inhibitors do have safety issues, but there are no new safety signals.

Dermatology Times: In your opinion, what are some of the possible real-world applications of having upadacitinib for vitiligo?

Hamzavi: When you have a condition that's so disfiguring and it's urgent, One of the most important things is to counsel patients. And this drug takes time to work. And if you're going to use a drug for a long time, how safe is it? And then how do you encourage patients to continue to use it? So, the fact that you're seeing the first response at 6 months, you're seeing a better response at 52 weeks and if it's going to follow what we know already from the other treatment interventions such as topical and phototherapy, the treatment responses will continue to improve even past 52 weeks. And then you also want to make sure this medication is safe. And the fact that there are no new safety signals, as this medication is in the JAK category, there are safety issues, we have not seen new safety signals, it gives us some confidence that the phase 3 trials will be effective. You have to take time with medication, but you have some assurance that at least initially, it seems to be this as the same safety profile as the other treatment indications. And then hopefully, we can figure out how to make the pigment come back faster. But the fact that the patients were noticing a difference, that was a positive finding. So exciting. And then the last part is the drop off, there was an improvement in the higher dose, and then there's a plateau. Well, we don't want to give a medication at a high rate unless we have to. And it has to be justified. Well, it seems that they found a good dose for the medication. So, lots of interesting findings that will hopefully help patients in the very, very near future.

[Transcript lightly edited for space and clarity.]


Passeron T, Ezzedine K, Hamzavi I, et al. Efficacy and safety after 52 weeks of once-daily upadacitinib in adults with extensive non-segmental vitiligo (NSV): final results from a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose‑ranging study. Presented at: 2024 American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, California.

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