Risks and Benefits of JAK Inhibitors for Vitiligo
METHODOLOGY:
Researchers conducted three meta-analyses of 19 studies to determine the safety and efficacy of JAK inhibitors in patients with vitiligo treated with oral or topical JAK inhibitors with or without conventional therapy.
Three distinct analyses were conducted, with data analysed from randomised controlled trials (RCTs), four single-arm trials, and a novel cohort of JAK inhibitor–treated patients from case reports and case series.
RCTs used topical ruxolitinib cream with placebo or vehicle cream as a comparator. Single-arm trials mostly used topical JAK inhibitors, whereas the novel cohort used oral JAK inhibitors.
Primary efficacy outcomes were a 75% improvement in the Facial Vitiligo Area Scoring Index (F-VASI75), mean percentage change in the VASI, and percentage of repigmentation in vitiligo lesions.
TAKEAWAY:
A meta-analysis of three RCTs showed that patients treated with topical JAK inhibitors were more likely to achieve F-VASI75 than those using vehicle cream (risk ratio [RR], 3.47; 95% CI, 0.98-12.22; P = .051), with no significant difference in adverse events between groups (RR, 1.27; 95% CI, 0.88-1.82).
= .051), with no significant difference in adverse events between groups (RR, 1.27; 95% CI, 0.88-1.82). The pooled analysis of four single-arm trials demonstrated a mean percentage change in the VASI of 43.79% (95% CI, 0.71-0.93; P < .001).
< .001). An analysis of the novel cohort revealed significantly increased repigmentation in patients treated with JAK inhibitors alone (48.7%; P = .0018) and in those treated with JAK inhibitors and narrowband ultraviolet B therapy (63.7%; P < .0001).
= .0018) and in those treated with JAK inhibitors and narrowband ultraviolet B therapy (63.7%; < .0001). Topical JAK inhibitors generally exhibited a more favourable safety profile; however, oral JAK inhibitors were associated with risks for immunosuppression, cardiovascular events, and haematopoietic disorders.
IN PRACTICE:
"Although topical ruxolitinib demonstrated encouraging outcomes, its results in RCTs did not reach statistical significance. However, findings from single-arm trials and case studies revealed substantial repigmentation, particularly when oral JAKis [JAK inhibitors] were administered alongside other therapeutic interventions," the authors wrote. "Future RCTs are essential to evaluate long-term safety, refine optimal application protocols and establish standardised outcome measures for combination therapies, ultimately improving treatment strategies for vitiligo," they concluded.
SOURCE:
This study was led by Alzahra A. Mohammed, Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University in Budapest, Hungary. It was published online on May 07, 2025, in Dermatology and Therapy .
LIMITATIONS:
The analysis was constrained by the small number of RCTs available and challenges in data collection from case reports due to heterogeneity in outcome reporting. Clinically meaningful thresholds for improvement were inconsistently followed across case reports and single-arm trials, limiting their integration. Analysis of the novel cohort was further limited by potential reporting biases and small sample size, and follow-up durations of single-arm trials and the novel cohort were insufficient for a comprehensive analysis of adverse events or long-term safety concerns.
DISCLOSURES:
This study received funding through a grant from the EU Horizon 2020 research and innovation programme. The Hungarian Centre of Excellence for Molecular Medicine covered publication fees. The authors reported no relevant conflicts of interest.
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