The efficacy and safety of minocycline, metronidazole, ivermectin, and azelaic acid in moderate-to-severe papulopustular rosacea: A systematic review and network meta-analysis.

Background: There are multiple topical agents for papulopustular rosacea (PPR), but the most effective for the management of moderate-to-severe PPR remains unknown. Objective: To compare the efficacy and safety of topical agents for moderate-to-severe PPR. Methods: Medline, Embase, and CENTRAL databases were searched. The efficacy of topical agents was explored through frequentist network meta-analysis using random-effects model. Treatments were ranked using net rank function, yielding P scores. Results: Nineteen randomized control trials (RCTs) that enrolled and 8208 participants were deemed eligible. Azelaic acid 20% yielded the highest effect size (OR = 8.54, 95% CI: 2.48-29.45) and highest P-score (P score = 0.97) with respect to improvement in investigator global assessment (IGA) score. Azelaic acid 15%, Metronidazole 0.75%, and Ivermectin 1% yielded comparable effect sizes. Azelaic acid 15% yielded statistically significant odds ratio (OR = 1.95, 95% CI: 1.30-2.93, P score = 0.14) for adverse events. Adverse event risk for other topical agents was not significant. Limitation: The sample size was limited for some of the topical agents. Also, many clinically important outcomes were overlooked by most of the included RCTs. Conclusion: Azelaic acid 20% was the most effective in improving IGA score for moderate-to-severe PPR and azelaic acid 15% as having the highest adverse event profile.