Oral ritxitinib combined with nbUV-B accelerates pigmentation in patients with non-segmental vitiligo

Recent research into vitiligo has focused on better understanding the autoimmune disease and developing treatments that are best suited for patients. Given its severe psychological effects, including depression, anxiety, impaired personal and social relationships, negative self-esteem, and impaired quality of life, vitiligo is in urgent need of additional treatment options. Clinically, vitiligo is classified as segmental (i.e., it affects only one side of the body or a specific area, such as the hands or face) or non-segmental vitiligo (NSV; i.e., depigmented patches appear symmetrically on various parts of the body, face, hands, and feet). NSV is the most common type of vitiligo.

Current vitiligo treatments aim to restore skin tone and even skin tone, but results may vary. Common treatments include topical, oral, or injectable corticosteroids, calcineurin inhibitors, and narrowband UV-B (nbUV-B) phototherapy, but there are currently no approved systemic drug treatments for NSV. New advances in skin repigmentation treatment include the introduction of the US Food and Drug Administration-approved topical ruxolitinib (Opzelura) 1.5% cream and oral Janus kinase (JAK) inhibitors such as Ritlecitinib, upacitinib (Rinvoq), and polyvitinib (formerly INCB54707), these drugs have shown promising results in phase 2 studies. Research confirms the autoimmune nature of vitiligo and identifies key molecular mechanisms involved in melanocyte destruction, paving the way for more targeted treatments. Povorcitinib and upadactinib (JAK1 inhibitors) are being evaluated as monotherapy in Phase 3 studies, along with the anti-interferon-alpha antibody anifrolumab-fnia (Saphnelo); afamelanotide (Scenesse), a synthetic hormone; and the JAK1/2 inhibitor baricitinib (Olumiant) in combination with nbUV-B in Phase 2 and 3 studies.

A pilot study was also conducted to investigate the combination of the PDE4 inhibitor apremilast (Otezla) with nbUV-B. Advances in light therapy, including the ability to do it at home, have made treatments more accessible and convenient. Skin grafting technology also offers an option for some patients. There is growing awareness of the psychological impact of vitiligo and the importance of providing supportive care, including cognitive behavioral therapy and support groups.

Phase 2b clinical trial (NCT03715829) of ritixitinib, an oral JAK3/TEC family kinase inhibitor, in adult patients with active NSV. Ritexitinib is highly selective for the other three JAK isoforms (JAK1, JAK2 and TYK2) and a broader range of human kinases. Ritexitinib 50 mg daily dose will receive marketing approval for the treatment of severe alopecia areata in the United States and the European Union in 2023, and has been approved in Japan, China, the United Kingdom, and Canada. RitexitinibCurrently ongoingPhase 3 study of NSV.

In a Phase 2b vitiligo study, ritixitinib 50 mg with or without a loading dose of 100 or 200 mg once daily was effective and well tolerated over 48 weeks of treatment in adults with active NSV, as measured by the Facial Vitiligo Area Score Index and Patient Global Impression of Change Scale. At the molecular level, skin biopsy samples showed significant dose-dependent downregulation of T cell activation, natural killer cells, cytotoxicity, type 1 immunity, and type 2 immunity markers in response to ritixitinib. In this study, ritixitinib also demonstrated efficacy in stable and active vitiligo lesions by reducing type 1 and type 2 immunity. Ritexitinib also showed similar efficacy. Fitzpatrick Safety Analysis for Skin Types I to VI.

During the extension period of the study, patients had the opportunity to receive additional ritixitinibtreatment with or withoutnbUV-B phototherapy. Overall, this study suggests that ritixitinib is a promising new treatment for NSV. Ritexitinib alone can effectively improve repigmentation, but when used in combination with nbUV-B, the efficacy results are more significant. Patients who received the combination therapy had greater improvements in facial and systemic pigmentation than those who received ritixitinib alone. Specifically, combination treatment resulted in an average improvement in facial pigmentation of 69.6%, compared with monotherapy with ritexitinib55.1%. In addition, the combination treatment of ritixitinib and nbUV-B was well tolerated and provides a new method to improve the prognosis of patients with vitiligo.

The Phase 3 ritixitinib program consists of 3 studies designed to evaluate the efficacy, safety and tolerability of ritixitinib at doses of 50 mg and 100 mg daily in adult and adolescent patients with NSV. These studies are Tranquillo (NCT05583526), u200bu200bTranquillo LTE (NCT06163326), and Tranquillo 2 (NCT06072183). The primary goal of the program is to demonstrate statistically significant and significant pigmentation compared with placebo, with a favorable benefit-risk profile.

In vitiligo, it may take up to1 year of treatment to achieve meaningful pigmentation. Therefore, a two-step approach is needed. The first treatment focuses on reducing inflammation and stopping the destruction of melanocytes, while the second focuses on inducing melanocyte growth and spread. Therefore, combination treatment with nbUV-B is expected to speed up the response, as the immunomodulator is thought to affect the first step of treatment, while phototherapy will aid the second step.

The increased interest in combination therapies is also based on preliminary data suggesting that novel immunomodulatory drugs combined withnbUV-B phototherapy show enhanced repigmentation by taking advantage of the potential additive or even synergistic effects of the two treatments. Combination therapy can provide rapid and clinically significant pigmentation, which can significantly improve patients' quality of life.

Ongoing clinical trials in vitiligo are generating great interest and optimism about better treatment outcomes. Key expectations include enhanced repigmentation, safety and rapid efficacy. Additionally, additive or synergistic effects are expected when used in conjunction with nbUV-B phototherapy, especially in difficult-to-treat areas such as the hands and feet.

Reference materials:https://www.dermatologytimes.com/view/oral-ritlecitinib-plus-nbuv-b-accelerates-repigmentation-in-nonsegmental-vitiligo