Efficacy and Safety of Topical Tretinoin Monotherapy versus Vehicle in the Treatment of Acne Vulgaris: A Meta-Analysis of Randomised Controlled Trials

Abstract

Background: Topical tretinoin is a guideline-endorsed first-line comedolytic retinoid for acne vulgaris, yet the magnitude of its benefit over vehicle across formulations, its expression in absolute terms, and its performance in paediatric skin have not been isolated in a focused pairwise synthesis.

Objective: To estimate the effect of topical tretinoin monotherapy versus vehicle on investigator-rated treatment success in facial acne vulgaris.

Methods: PubMed/MEDLINE, Scopus, Web of Science and the Cochrane Library were searched from database inception, and ClinicalTrials.gov and regulatory product labels were interrogated to recover event-level data. Randomised, double-blind, vehicle-controlled trials (or vehicle-controlled arms) of topical tretinoin monotherapy in facial acne were eligible. The primary outcome was treatment success at approximately 12 weeks. Two reviewers independently screened, extracted data and applied the Cochrane RoB 2.0 tool. Risk ratios (RRs) were pooled with a DerSimonian–Laird random-effects model; heterogeneity used I² and a prediction interval.

Results: Nine trial datasets (4,429 participants; 2,537 tretinoin, 1,892 vehicle) were pooled. Tretinoin significantly increased treatment success (RR 1.83, 95% CI 1.48–2.27; p < 0.001), with moderate heterogeneity (I² 36.7%) and a prediction interval (1.11–3.04) that excluded the null. The absolute success rate rose from 10.4% with vehicle to 18.4% with tretinoin (number needed to treat approximately 12). The estimate was stable in leave-one-out (RR 1.75–1.95) and combined-programme (RR 1.80) analyses and did not differ across formulations (p = 0.17). Cutaneous adverse events were mild, transient and application-site limited.

Conclusion: Topical tretinoin monotherapy roughly doubled the relative likelihood, and raised the absolute likelihood by about 8 percentage points, of treatment success versus vehicle, with predictable, self-limiting local tolerability that extended to preadolescent skin, supporting its first-line and maintenance positioning.