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What’s New and Hot in Vitiligo

Treatment of vitiligo can be challenging, but with promising new treatments emerging, the therapeutic options for patients are increasing

By Jeanette Zambito, MD, MS | July 01, 2023

Vitiligo is one of the most common conditions treated by dermatologists, and one that has a significant psychosocial impact on patients. The treatment of vitiligo can be challenging, and treatment results are often disappointing. However, there are several new treatments that offer hope to patients who suffer from this chronic, and often stigmatizing, condition. 

JAK inhibitor ruxolitinib approved as topical treatment 

In July 2022, the FDA approved topical ruxolitinib (Opzelura) for the treatment of nonsegmental vitiligo in patients 12 and older. Topical ruxolitinib is the first FDA-approved treatment for repigmentation in patients with vitiligo.2 It is a JAK inhibitor that functions by inhibiting JAK1 and JAK2 protein kinases, leading to a decrease in proinflammatory cytokines and chemokines.3 

In two phase 3 randomized clinical trials, twice daily application of ruxolitinib cream for 24 weeks resulted in greater repigmentation of facial skin in patients with vitiligo compared to a vehicle cream. The most common side effects were application-site acne and pruritus.4 Unlike topical steroids, which have historically been one of the mainstays of vitiligo treatment, topical ruxolitinib does not cause striae or atrophy. Stinging or burning at the application site, an oft-reported side effect with topical calcineurin inhibitors, was infrequent with ruxolitinib cream.4 

While long-term safety data for topical JAK inhibitors is lacking, trial results found that the mean plasma concentrations of ruxolitinib were well below 281 nM, a proxy for evaluating JAK-related myelosuppression in bone marrow.4 

Clinical trials underway investigating more JAK inhibitors for vitiligo 

Clinical trials are ongoing to evaluate the efficacy and safety of other JAK inhibitors for vitiligo, including studies on oral JAK inhibitors, and several case reports have shown efficacy of oral tofacitinib and oral ruxolitinib in vitiligo.5 A recent phase 2B study of ritlecitinib, an oral JAK3/TEC inhibitor, found it to be well-tolerated and efficacious in the treatment of patients with active nonsegmental vitiligo over the course of 48 weeks.6 

Promising developments in alpha-melanocyte-stimulating hormone analogues Alpha-melanocyte-stimulating hormone analogues are another promising area of drug development in vitiligo. Afamelanotide is a synthetic analogue of alpha-melanocyte-stimulating hormone that stimulates melanogenesis. In a double-blinded, multicenter study, patients treated with NB-UVB plus afamelanotide achieved repigmentation rates higher than those seen with NB-UVB alone.7 Studies are currently underway to evaluate afamelanotide as monotherapy for vitiligo.8 

The future of vitiligo treatment 

While there is still no cure for vitiligo, there are a number of emerging new treatment options for patients. Dermatologists should be aware of the advances in treatment within the field so they can offer patients access to the full complement of available therapeutic options. 

References
  1. Narayan VS, Uitentuis SE, Luiten RM, Bekkenk MW, Wolkerstorfer A. Patients' perspective on current treatments and demand for novel treatments in vitiligo. J Eur Acad Dermatol Venereol. 202;35(3):744-748. doi:10.1111/jdv.16927 
  2. Sheikh A, Rafique W, Owais R, Malik F, Ali E. FDA approves ruxolitinib (Opzelura) for vitiligo therapy: A breakthrough in the field of dermatology. Ann Med Surg (Lond). 2022;81:104499. doi:10.1016/j.amsu.2022.104499 
  3. Haq M, Adnan G. Ruxolitinib. In: StatPearls [Internet]. StatPearls Publishing; 2023. Updated Sept 27, 2022. Accessed June 29, 2023. https://www.ncbi.nlm.nih.gov/books/NBK570600/ 
  4. Rosmarin D, Passeron T, Pandya AG, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med. 2022;387(16):1445-1455. doi:10.1056/NEJMoa2118828 
  5. Harris JE, Rashighi M, Nguyen N, et al. Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad Dermatol. 2016;74(2):370-1. doi:10.1016/j.jaad.2015.09.073 
  6. Ezzedine K, Peeva E, Yamaguchi Y, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. J Am Acad Dermatol. 2023;88(2):395-403. doi:10.1016/j.jaad.2022.11.005 
  7. Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE; Vitiligo Working Group. New discoveries in the pathogenesis and classification of vitiligo. J Am Acad Dermatol. 2017;77(1):1-13. doi:10.1016/j.jaad.2016.10.048 
  8. Clinuvel. First vitiligo patient enrolled in afamelanotide monotherapy study. Clinuvel. Published October 20, 2022. Accessed June 29, 2023. https://www.clinuvel.com/first-vitiligo-patient-enrolled-in-afamelanotide-monotherapy-study-20221020/
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