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Half of patients with vitiligo achieved 90% improvement in facial repigmentation and more than a fourth had 75% improvement in total body repigmentation after long-term treatment with topical ruxolitinib (Jakafi), a randomized controlled study showed.

Measurable improvement occurred within 24 weeks and progressively increased during follow-up to 52 and 104 weeks. At the 104-week assessment, 83.6% of patients had at least 50% improvement in facial vitiligo, including 52% who had 90% improvement. With respect to total-body involvement, 58.2% of patients had at least 50% improvement at 104 weeks and 27.3% had 90% improvement.

Additionally, 43.6% of the patients' physicians rated facial skin status as clear or almost clear, and a majority of patients said their condition was very much or much improved, as reported during the American Academy of Dermatology virtual meeting.

"Treatment with ruxolitinib cream produced substantial facial and total body repigmentation of vitiligo lesions through 104 weeks of treatment," concluded John E. Harris, MD, PhD, of the University of Massachusetts Medical School in Worcester, and coinvestigators, in a poster presentation. "Longer duration of therapy was associated with greater repigmentation ... at weeks 24, 52, and 104. Ruxolitinib cream was well tolerated over a 2-year period, and no treatment-related serious AEs [adverse events] were reported."

A separate analysis of patients treated with topical ruxolitinib and phototherapy showed even greater improvement with the addition of narrow-band ultraviolet-B (nbUVB) from weeks 52 to 104.

Vitiligo is a chronic autoimmune disease, with pathogenesis driven by interferon-gamma, which leads to activation of signaling pathways regulated by Janus kinase (JAK) 1 and 2. In a , a topical formulation of ruxolitinib, a JAK1/2 inhibitor, produced significant repigmentation over 52 weeks. Harris and colleagues reported findings from continued follow-up to week 104.

Patients eligible for the study had depigmentation of at least 0.5% of body surface area on the face and at least 3% on nonfacial areas. Key exclusions included confounding dermatologic conditions, prior JAK inhibitor exposure, and use of biologics, experimental therapy for vitiligo, phototherapy, or immunomodulating agents.

Patients were randomized to four concentrations of ruxolitinib cream or cream vehicle, applied once or twice daily. At 24 weeks, patients in the vehicle arm were re-randomized to one of the three higher doses of ruxolitinib, as were patients who did not have at least 25% improvement with the lowest ruxolitinib concentration. The remaining patients continued treatment with their original ruxolitinib doses to week 52.

Patients who completed 52 weeks of treatment had the option to continue open-label treatment with 1.5% ruxolitinib for an additional 104 weeks (156 weeks total follow-up). Optionally, patients could choose to have concomitant nbUVB during open-label treatment.

Vitiligo status was assessed by the facial (F) and total (T) Vitiligo Area Scoring Index (F or T-VASI) for improvement of ≥50% (VASI50), ≥75% (VASI75), and ≥90% (VASI90). Response was also assessed by the Physician's Global Vitiligo Assessment (PhGVA), with response defined as clear or almost clear skin. Patients rated their treatment outcome by means of the Patient Global Impression for Vitiligo (PaGIC-V), with response defined as very much or much improved.

The report by Harris and colleagues focused on 55 patients who completed 104 weeks of treatment. The results showed that 38 of 94 patients (40.4%) had F-VASI50 responses at 24 weeks, increasing to 50.0% at 52 weeks, and 83.6% (46 of 55) at 104 weeks.

F-VASI75 response rates increased from 21.3% at 24 weeks to 37.2% at 52 weeks, and 65.5% at 104 weeks. The F-VASI90 response at 104 weeks was 52.7% as compared with 11.7% at 24 weeks.

T-VASI response rates also improved over time. T-VASI50 response increased 13.8% at 24 weeks to 30.9% at 52 weeks to 58.2% at 104 weeks. Corresponding values for T-VASI75 were 2.1%, 9.6%, and 27.3%. F-PhGVA response was 10.6% at 24 weeks, increasing to 21.5% at 52 weeks and 43.6% at 104 weeks. PaGIC-V responses stood at 26.4% at 24 weeks and increased to 42.3% at 52 weeks and 55.6% at 104 weeks.

Patients initially randomized to ruxolitinib 1.5% BID and who continued treatment to 104 weeks had similar progressive improvement, Harris and co-authors reported. F-VASI50, 75, and 90 responses at 104 weeks were 89.5%, 73.7%, and 57.9%. The T-VASI50 response rate was 63.2%, and 26.3% of patients had T-VASI75 responses.

The most common treatment-emergent adverse events (all grades) during the open-label phase were sinusitis (5.2%), nasopharyngitis (3.9%), upper respiratory tract infection (3.9%), and oral herpes (3.9%).

The analysis of nbUVB add-on therapy during open-label treatment with 1.5% ruxolitinib included 19 patients, as reported by Amit G. Pandya, MD, of Palo Alto Foundation Medical Group in California and the UT Southwestern Medical Center in Dallas, and coinvestigators.

F-VASI50 responses increased from 68% at 52 weeks to 89% at 104 weeks. F-VASI75 responses increased from 42% to 68% and F-VASI90 responses from 21% to 58%. T-VASI50 response rates were 42% at 52 weeks and 68% at 104 weeks, and the proportion of patients with T-VASI75 responses increased from 0% to 32%.

In a small subgroup of patients who did not achieve F-VASI50 responses at 24 weeks, similar improvement from 52 to 104 weeks was observed with the add-on phototherapy.

JAK inhibitors are not FDA approved for vitiligo and continue to be evaluated in clinical trial settings. Additionally, the topical formulation used in the studies has to be prepared at a compounding pharmacy, said vitiligo specialist , of Innovative Dermatology in Plano, Texas, and UT Southwestern Medical Center.

"We need more data, but at this point, they [JAK inhibitors] are promising," he told MedPage Today. "I typically reserve the treatment for smaller body surface areas because the product is expensive. If you try to use it on someone who has vitiligo all over their body, it becomes cost prohibitive.

"That said, I find it very helpful. I have combined it with UV light, and we now have data to show that these agents have a kind of synergistic effect with UV light. That doesn't mean the products don't work on their own, but we think that UV light may actually make them work better."

More than one JAK inhibitor is being evaluated in vitiligo. Different drugs target different components of the JAK signaling pathway, and more studies are needed to determine how to make optimal use of the topical products, said Desai.

"I think the future of this is very bright," he added. "Topical JAK inhibitors are being looked at in other inflammatory skin diseases, like alopecia areata, atopic dermatitis, and psoriasis. The more we learn about these products, the more exciting the work becomes because we're really getting to see they have a broad (clinical) area and a broad scope."