Intralesional corticosteroid combination therapy shows odds ratio of 2.71 for improved keloid outcomesCombining treatments may improve results for patients with keloids

Keloids continue to present a therapeutic challenge despite several proposed treatment modalities, and there is a lack of current evidence-based guidelines to inform disease management. Therefore, we conducted this systematic review and meta-analysis to compare intralesional corticosteroid monotherapy against combination therapies containing intralesional corticosteroids regarding their efficacy and safety. We searched PubMed, Scopus, and Web of Science using the Medical Subject Headings (MeSH) terms with the following keywords: “Corticosteroids” AND “Keloid” AND “Intralesional” from inception until May 2026 to identify the studies included in this systematic review and meta-analysis. The screening process was conducted based on inclusion and exclusion criteria established using the PICOS criteria as follows: P (population): patients with keloids; I (intervention): a combination of intralesional corticosteroids and any other therapy or drug; C (comparison): intralesional corticosteroids alone; O (outcomes): any efficacy and safety outcome; and S (study design): randomized controlled trials, non-randomized trials, and observational cohort studies. A total of 20 studies were included in the current systematic review and meta-analysis, comprising 15 randomized controlled trials, 2 non-randomized controlled trials, and 3 cohort studies. The analysis of each outcome included only a subset of the included studies, as not all studies reported all outcomes. The analysis favored combination treatment over intralesional corticosteroids alone regarding clinical improvement or efficacy, with an odds ratio of 2.71 (95% CI: 1.8, 4.09; p  Combination therapies with intralesional corticosteroids showed greater efficacy and safety than monotherapy across various outcomes. Subgroup analysis indicates that effects vary by co-intervention: corticosteroids (CS) plus 5-fluorouracil (5-FU) had favorable efficacy, adverse events, and height outcomes; Vancouver Scar Scale change favored CS plus excision, 5-FU, and platelet-rich plasma. Significant subgroup differences, heterogeneity, and limited data warrant cautious interpretation. Clinical and methodological differences, treatment variations, and inclusion of non-randomized studies limit certainty and generalizability. Evidence does not universally favor combination therapies over monotherapy. Among adjuncts, 5-FU combinations show consistent benefit, but more trials are needed to identify the best regimen. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261439889, identifier CRD420261439889.