Comparing the Efficacy and Safety of Monotherapy Triamcinolone Acetonide or 5-Fluorouracil versus Combination Triamcinolone Acetonide and 5-Fluorouracil in the Treatment of Hypertrophic Scars and Keloids: A Systematic Review and Meta-analysis

PURPOSE: Keloids and hypertrophic scars predispose to physical and psychosocial problems. Combination triamcinolone acetonide (TAC) with 5-fluorouracil (5-FU) is presumed to enhance the treatment of pathological scars, although there is a dearth of evidence. We aimed to evaluate the efficacy and complication rates of combination intralesional TAC and 5-FU in comparison to monotherapy intralesional TAC or 5-FU for the treatment of hypertrophic scars and keloids. METHODS: The protocol was published a priori on PROSPERO (CRD42021271406). EMBASE, MEDLINE and CENTRAL were searched by two independent reviewers. Primary outcomes were treatment efficacy (defined as 51- 100% improvement) and reduction in scar height. Study quality and risk of bias were assessed using GRADE and Cochrane’s risk of bias tool, respectively. RESULTS: Of 641 articles screened, 12 studies involving 847 patients were included. There were 11 randomised controlled trials (RCT) and 1 non-randomised study of interventions. There were 6 and 8 studies comparing combination intralesional TAC and 5-FU versus monotherapy intralesional 5-FU and intralesional TAC, respectively. The combination group demonstrated superior objective treatment efficacy when compared to the monotherapy intralesional TAC group (RR 1.45, 95% CI [1.27, 1.64], P<0.001) and monotherapy intralesional 5-FU group (RR 1.46, 95% CI [1.24, 1.71], P<0.001). The combination group exhibited a greater reduction in scar height when compared to the monotherapy intralesional TAC group (SMD -0.48, 95% CI [-0.73, -0.23], P=0.006). The most consistently reported complication was telangiectasia, occurring at rates of 5.63% and 23.5% for combination and monotherapy intralesional TAC, respectively (RR 0.25, 95% CI [0.12, 0.52], P<0.001). There were no consistently applied validated patient reported outcome measures (PROMs). CONCLUSION: Combination intralesional TAC and 5-FU demonstrated superiority to the respective monotherapy of these agents in objective measures of treatment efficacy, scar height reduction and adverse complications. The paucity of PROMs should be urgently addressed in subsequent clinical trials.