Efficacy and Safety of Small Molecule Inhibitor Therapies for Vitiligo: A Systematic Review

The latest advances in the treatment of vitiligo involve the introduction of Janus kinase inhibitors (JAKI) and small molecule inhibitors (SMI). These modern treatment modalities target specific inflammatory pathways that can improve outcomes for vitiligo in adults, adolescents, and children.

We did a literature search among PubMed, Scopus, and Web of Science, utilizing PRISMA guidelines. Articles included in the study were those reporting systemic medications using JAKI and SMI for vitiligo, categorized into subgroups of children (2-12), adolescents (12-18), and adults (over 18). We extracted information based on patient demographics, treatment regimens, efficacy outcomes, adverse effects, and follow-up data.

After screening 987 studies, a total of 25 articles met the inclusion criteria and were included. The analysis demonstrated that JAKI, as well as the phosphodiesterase-4 Inhibitor (PDE4 Inhibitor), apremilast, showed notable efficacy in the treatment of vitiligo across various age groups. Among these, ritlecitinib was the most extensively studied, showing significant improvements in both Facial-VASI and Total-VASI scores, especially when combined with NB-UVB phototherapy. Tofacitinib demonstrated up to 75% repigmentation, particularly in sun-exposed areas and pediatric populations, with higher efficacy noted when used alongside phototherapy. Upadacitinib showed ≥ 35% improvement in Facial-VASI scores, though higher doses were associated with increased adverse events, including a serious nonfatal ischemic stroke. Baricitinib led to > 50% VASI improvement in 70.6% of patients when combined with NB-UVB. Apremilast showed partial disease control and up to 61.5% repigmentation, though it was generally less effective than corticosteroids in halting progression.

JAKI and SMIs appear to be promising treatment options for vitiligo in adults, adolescents, and children, offering better efficacy than traditional treatments. However, some treatments like Apremilast had conflicting results about efficacy in vitiligo. Although these are notable findings, further research is required to establish their long-term safety, particularly in children and adolescents.