Comparative Efficacy and Recurrence Risk of Intralesional Therapies for Hypertrophic Scars and Keloids: A Network Meta-Analysis

Abstract Hypertrophic scars and keloids are fibroproliferative disorders arising from aberrant wound healing, often leading to aesthetic disfigurement, functional impairment, and psychosocial burden. Intralesional therapies remain a mainstay of treatment, yet the comparative efficacy and recurrence profiles of different agents have not been definitively established. We conducted a systematic search of PubMed (National Institutes of Health, Bethesda, MD), Cochrane Library (Wiley, Hoboken, NJ), US National Institutes of Health Ongoing Trials Register, EMBASE (Elsevier, Amsterdam, the Netherlands), and Google Scholar (Alphabet, Inc., Mountain View, CA) from inception through May 2025, restricted to English-language publications, to identify randomized controlled trials comparing two or more intralesional treatments for hypertrophic scars or keloids. Twenty-four eligible trials were included in a frequentist random-effects network meta-analysis integrating direct and indirect comparisons. Pooled estimates demonstrated that triamcinolone acetonide combined with 5-fluorouracil (TAC+5-FU) achieved the most consistent improvements in treatment efficacy and recurrence control. Botulinum toxin A (BTA) ranked highest in treatment response but did not significantly reduce recurrence risk. Verapamil (VER) was associated with significantly lower efficacy compared with TAC, whereas bleomycin (BLM) and 5-FU monotherapies provided intermediate outcomes without statistical superiority. Overall, TAC+5-FU offered the most favorable balance between efficacy and recurrence reduction, while BTA showed strong response efficacy. These findings provide a comprehensive synthesis of intralesional therapies for hypertrophic scars and keloids, support the consideration of combination regimens in scar management, and underscore the need for further well-designed head-to-head trials with standardized endpoints to refine individualized treatment strategies.