Topical Ivermectin in the Treatment of Papulopustular Rosacea: A Systematic Review of Evidence and Clinical Guideline Recommendations

Introduction: Rosacea is a chronic inflammatory skin disease with different phenotypes. There is accumulating evidence that the commensal Demodex mite is linked to papulopustular rosacea. Established treatment options, including topical metronidazole, azelaic acid, and tetracyclines, are thought to work through their anti-inflammatory effects. However, none of these therapies have been shown to be curative and are associated with frequent relapses. Therefore, new and improved treatment options are needed. Topical ivermectin 1.0% cream is a new option having both anti-inflammatory and acaricidal activity against Demodex mites which might pave the way to a more etiologic approach. Its use has now been widely adopted by clinical guidelines. The objective was to review the evidence and clinical guideline recommendations concerning ivermectin 1.0% cream in the treatment of papulopustular rosacea. Methods: A systematic review of both medical literature and clinical guideline recommendations was conducted. Numbers needed to treat (NNT) were calculated for relevant dichotomous outcomes (e.g., relapse rate and achieving full lesion clearance) to compare ivermectin with other established treatment options for rosacea. Results: The search identified three randomized trials, three extension studies, and two meta-analyses. Ivermectin has only been tested in moderate-to-severe papulopustular rosacea. Ivermectin is an effective treatment option for papulopustular rosacea and seems to be more effective than metronidazole (NNT = 10.5) at 12 weeks of treatment. Although ivermectin was numerically more effective than metronidazole at week 36 in preventing relapse (NNT = 17.5), relapse after discontinuation of treatment in both groups was common with 62.7% and 68.4% of patients relapsing. Based on limited generalizability of available evidence, clinical guidelines have yielded different treatment algorithms and, in some areas, conflicting recommendations. Conclusion: Topical ivermectin is an effective option in the treatment of papulopustular rosacea. Although ivermectin seems to be more effective than topical metronidazole, with both treatment options about two-thirds of patient relapsed within 36 weeks after discontinuation of treatment. More research is needed to establish the clinical benefit of ivermectin's acaricidal action in preventing relapse compared to other non-etiologic treatment approaches.