Comparative efficacy of intralesional therapies for keloid scars: a network meta-analysis

Keloids are pathological scars causing pain, pruritus, and emotional distress. While common treatments exist, emerging options such as insulin and botulinum toxin A (BTX-A) are underrepresented in comparative analyses. This network meta-analysis (NMA) aimed to evaluate the efficacy and safety profiles of various intralesional therapies for keloid scars. A PRISMA-guided search across seven databases was conducted on July 2025 and preregistered on PROSPERO (CRD420251088758). Included studies were randomized, non-randomized, and crossover trials of intralesional therapies. Pairwise and NMA were conducted for efficacy (keloid size/volume reduction), recurrence, and safety (adverse effects). Treatment rankings were based on surface under the cumulative ranking curve (SUCRA) scores. Statistical significance was set at (p < 0.05). From 51 studies (3234 participants, 23 interventions), 5-fluorouracil (5-FU) + corticoids significantly improved keloid reduction compared to corticoids alone (RR = 1.59; 95% CI: 1.31–1.92; p < 0.01), with 5-FU + corticoids + YAG:Laser (RR = 2.73; 95% CI: 1.36–5.48; p < 0.01) showing an even greater effect. SUCRA values indicated that 5-FU + corticoids + YAG:Laser (0.95), vitamin D + platelet rich plasma (0.83), and 5-FU + corticoids (0.78) had the highest probability of effectiveness. For recurrence, no significant differences were found across interventions, suggesting insufficient evidence. Regarding adverse effects, a significant risk reduction was found for BTX-A (RR = 0.29; 95% CI: 0.09–0.95; p = 0.04) and Verapamil (RR = 0.35; 95% CI: 0.14–0.84; p = 0.01) compared to corticoids; others showed no significant effects. This NMA provides a comparative overview, indicating that combination therapies, most notably 5-FU + corticoids + YAG:Laser, offer the greatest benefit. While data for novel agents (insulin and BTX-A) suggest potential, further research with standardized methodologies and longer-term follow-up is crucial to define optimal treatment algorithms.