Efficacy and Safety of JAK Inhibitors in the Management of Vitiligo: A Systematic Review and Meta-analysis.

Introduction: Vitiligo, a chronic skin disease affecting 1-2% of the global population, is associated with significant impairment in quality of life. Current pharmacological treatment options have limited efficacy and considerable side effects. Recent studies have shown promising results when using Janus kinase inhibitors (JAKis). Despite these favourable findings, there remains a critical need for comprehensive data on the efficacy and safety of JAKi in the treatment of vitiligo.

Methods: Three databases were searched for studies on patients with vitiligo treated with oral or topical JAKi, with or without conventional therapy. Placebo or vehicle cream were comparators in randomised controlled trials (RCTs). Outcomes included a 75% improvement in Facial-Vitiligo Area Scoring Index (F-VASI), mean Vitiligo Area Scoring Index (VASI) improvement, repigmentation percentage and adverse events. We performed three analyses: one using RCT data, one from case reports and a novel cohort of JAKi-treated patients from case reports. The protocol is registered with PROSPERO (CRD42023445503).

Results: Among the 35 articles identified, 19 were included in the statistical analyses. A meta-analysis of three randomised controlled trials (RCTs) on topical Janus kinase inhibitors (JAKis) suggested that patients treated with JAKi were more likely to achieve Facial Vitiligo Area Scoring Index 75 (F-VASI75) than those using vehicle cream (risk ratio (RR) 3.47, 95% confidence interval (CI) 0.98-12.22), with no significant difference in adverse events between groups (RR 1.27; 95% CI 0.88-1.82). A meta-analysis of four single-arm trials showed a 43.8% mean Vitiligo Area Scoring Index (VASI) improvement (95% CI 0.71-0.93). A cohort (n = 28) from case reports and series revealed significant repigmentation increases of 48.7% and 63.7% (p = 0.0018; p < 0.001) in patients treated with JAKi alone or with narrowband ultraviolet B (UVB). However, data were insufficient to determine if combination treatments were superior to JAKi alone.

Conclusion: Our systematic review evaluated the efficacy and safety of JAKi for vitiligo using data from RCTs, single-arm trials and case reports. While topical ruxolitinib showed promising but non-significant results in RCTs, single-arm trials and case studies highlighted significant repigmentation, particularly with oral JAKis combined with other therapies. Oral JAKis showed effectiveness but require caution due to potential adverse effects such as immune suppression and cardiovascular risks. Furthermore, it is important to acknowledge that a considerable proportion of patients do not respond to these therapies. Additional RCTs are needed to address long-term safety, optimise application strategies and establish standardised endpoints for combination therapies.