Background Direct evidence comparing single‐agent and combination regimens for vitiligo is limited and often overlooks longitudinal outcomes. This study evaluated how combination therapy versus monotherapy influenced repigmentation, measured by the Vitiligo Area Scoring Index (VASI), in a real‐world clinical setting. Objective To compare the effectiveness of monotherapy versus combination therapy in vitiligo treatment using longitudinal VASI scores, adjusting for demographic and clinical confounders. Methods We retrospectively reviewed records from two tertiary centers in Saudi Arabia (Jan 2018–Dec 2023). A total of 500 patients (52% female; aged 1–75 years) contributed approximately 5,000 visit‐level VASI scores over 12 months. Treatment was classified as monotherapy ( n = 179) or combination therapy ( n = 321). Linear mixed‐effects models with random intercepts and patient‐specific slopes were applied. Fixed effects included therapy modality, visit order, age, sex, nationality, and vitiligo phenotype. Model selection was based on Akaike/Bayesian information criteria and likelihood ratio tests. Results The best‐fit model included a therapy‐by‐visit interaction. Combination therapy was associated with a 2.1‐point lower baseline VASI than monotherapy ( p < 0.001), with greater reductions over time (−0.31 per visit; p < 0.001). Genital, focal, and acrofacial types responded best; universal vitiligo worsened. Age predicted poorer response; sex and nationality were nonsignificant. ICC = 0.95; marginal and conditional R 2 were 0.42 and 0.97, respectively. Conclusion Combination regimens offer faster and more sustained VASI improvements than monotherapy, particularly in extensive or aggressive vitiligo. These findings support personalized treatment strategies incorporating NB‐UVB or JAK inhibitors and highlight the importance of phenotype‐based care. Further head‐to‐head trials and meta‐analyses are needed to refine regimen selection and address interpatient variability.
Molla et al. (Thu,) studied this question.