Topical ivermectin and encapsulated benzoyl peroxide (E-BPO) may offer greater short-term efficacy than metronidazole for adults with moderate-to-severe rosacea, according to a systematic review and network meta-analysis.
The analysis included 32 randomised controlled trials involving 11,399 adults with moderate-to-severe rosacea and compared 10 US Food and Drug Administration-approved topical treatments. Investigators searched CENTRAL, MEDLINE, Embase and Web of Science from database inception to August 2025. Outcomes were synthesised using random-effects network meta-analysis, with treatment rankings estimated using surface under the cumulative ranking (SUCRA) values.
The primary outcomes were change in inflammatory lesion count, Investigator Global Assessment (IGA) success and treatment discontinuation due to adverse events. Most included studies had follow-up periods of 8–16 weeks.
Topical Therapies for Rosacea Differ in Efficacy and Tolerability
Compared with metronidazole, both ivermectin and E-BPO achieved significantly greater reductions in inflammatory lesion counts. Ivermectin reduced lesion counts by a mean difference (MD) of 4.17 (95% CI 1.85–6.48), while E-BPO achieved an MD of 4.14 (95% CI 0.62–7.66). Both agents also increased the likelihood of achieving IGA success, with MDs of 10.31 (95% CI 2.85–17.77) for ivermectin and 15.51 (95% CI 2.35–28.68) for E-BPO.
Overall rates of treatment discontinuation due to adverse events were broadly similar across therapies. However, discontinuation was significantly more frequent with E-BPO than with metronidazole (MD 8.33; 95% CI 0.45–16.22), suggesting improved efficacy may come at the expense of tolerability for some patients.
The authors noted that evidence for patient-reported outcomes and clinician-assessed erythema was limited, preventing robust quantitative analysis of these measures.
The researchers concluded that topical ivermectin and encapsulated benzoyl peroxide appear to provide superior short-term efficacy among currently approved topical therapies for rosacea. However, they emphasised that longer-term comparative studies are needed to better define durability of response, safety and treatment tolerability, as well as to incorporate standardised patient-reported outcome measures into future clinical trials.
Reference
Amstutz AV et al. Topical preparations for moderate to severe rosacea treatment: a systematic review and network meta-analysis. JAMA Dermatol. 2026;DOI: 10.1001/jamadermatol.2026.2062.
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