For the roughly 16 million Americans living with rosacea, treatment decisions have long been complicated by a fragmented evidence base comparing individual agents against placebo rather than against each other. A head-to-head comparative ranking of topical therapies — including newer encapsulated formulations — has been conspicuously absent, leaving clinicians without clear guidance on optimal first-line choices.
This JAMA Dermatology systematic review and network meta-analysis synthesized randomized controlled trial data from databases including MEDLINE, Embase, CENTRAL, and Web of Science, with a search cutoff of August 2025. Restricted to adults with moderate-to-severe rosacea, the analysis applied random-effects network meta-analytic methods to simultaneously compare multiple topical agents across three primary outcomes: absolute inflammatory lesion count reduction, Investigator Global Assessment success rates, and treatment discontinuation due to adverse events. Surface under the cumulative ranking (SUCRA) values were used to probabilistically rank all included therapies, and certainty of evidence was graded via the GRADE framework. Notably, encapsulated benzoyl peroxide — a relatively novel formulation designed to reduce irritation through controlled release — was included alongside established agents such as ivermectin, azelaic acid, and metronidazole.
What makes this analysis meaningful beyond prior pairwise trials is the indirect comparison architecture: network meta-analysis allows inference about head-to-head differences even when direct RCT comparisons are unavailable. That methodological strength is important here because rosacea trials have historically been sponsor-driven and designed to beat placebo, not competitors. However, network meta-analyses remain bounded by the quality of the constituent trials, and if the included RCTs vary substantially in patient phenotype, disease duration, or baseline severity, heterogeneity can undermine ranking reliability. The inclusion of GRADE certainty ratings is a meaningful safeguard. For health-conscious adults managing rosacea, this type of comparative evidence — when the full results are available — should directly inform conversations with dermatologists about balancing clearance rates against skin tolerability.