A Review of Randomized Controlled Trials for Vitiligo Therapies Published Between 2013 and 2023

Vitiligo is a depigmentation disorder whose treatment remains a serious challenge. While it is generally accepted that topicals and phototherapy are helpful for generalized symmetric disease, randomized controlled trials (RCTs) provide the best evidence for treatment. Our objective was to identify and summarize RCTs for vitiligo from 2013 to 2023. A systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO) was performed per PRISMA guidelines. We searched CENTRAL, ClinicalTrials.gov, Embase, PubMed, and Web of Science for RCTs using keywords such as 'vitiligo' and/or 'treatment' or 'intervention.' A total of 652 studies underwent full-text review, and 151 studies met the inclusion criteria. We focused our study on RCTs using the vitiligo area scoring index (VASI) as the primary outcome measure, leading to 36 studies. We further narrowed our focus to studies that could be aggregated into the intervention categories: phototherapy and systemic combination therapy (n=10), topical and topical combination therapy (n=15), and systemic monotherapy (n=5).  Treated versus control subjects showed statistically improved VASI after the following interventions were added to phototherapy: oral psoralen, oral minipulsed prednisone, implanted afamelanotide, topical ethyl vanillate, topical bimatoprost, and oral vitamins A and E. Effective topical therapies were ruxolitinib, calcipotriol and betamethasone, tacrolimus and mometasone, and microdermabrasion and tacrolimus. None of the systemic monotherapies was superior to their corresponding comparator.