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: Papulopustular rosacea (PPR) is a common inflammatory cutaneous disease affecting the face. This network meta analysis compares the efficacy and safety of topical agents for PPR. Methods: Medline, Embase, and CENTRAL databases for randomized controlled was searched. Trials (RCTs) on different topical agents: minocycline (1%, 1.5%, and 3%), metronidazole (1%, 0.75%), azelaic acid (15%, 20%), and ivermectin (1%) for management of moderate-to-severe PPR and to evaluate success on the Investigator Global Assessment (IGA) score and adverse events. The efficacy of topical agents was explored through frequentist network meta analysis with random effects. Treatments were ranked using net-rank function, yielding P-scores. Results: Nineteen RCTs that enrolled 8208 participants were deemed eligible. For IGA outcome, azelaic acid 20% yielded the highest effect sizes (OR= 8.54, 95% CI: 2.48-29.45). Azelaic acid 15%, metronidazole 0.75%, and ivermectin 1% yielded comparable effect sizes. Minocycline 1% and 3% provided no improvement in moderate-to-severe papulopustular rosacea while minocycline 1.5% yielded a significant effect size (OR 1.73, 95% CI: 1.17 to 2.57). Azelaic acid 20% yielded the highest P-scores (P score = 0.97). Compared with the placebo, only azelaic acid 15% yielded a statistically significant odds ratio (OR= 1.95, 95% CI: 1.30-2.93, P score= 0.14) for adverse event risk. Adverse event risk for other topical agents was not significantly different from placebo. Conclusion: This network meta analysis demonstrated that azelaic acid 20% was the most effective topical agent in improving IGA score for moderate-to-severe PPR while AzA 15% exhibited the highest adverse event rate.