Topical ivermectin and encapsulated benzoyl peroxide demonstrate superior short-term efficacy compared with metronidazole in the treatment of adults with moderate-to-severe rosacea in a network meta-analysis, although encapsulated benzoyl peroxide is also associated with higher treatment discontinuation rates due to adverse events.
Pooled data from 32 randomized controlled trials evaluating 10 topical medications showed that compared with metronidazole-treated participants, those who received ivermectin saw greater reductions in lesion count (mean difference [MD], 4.17, 95 percent confidence interval [CI], 1.85–6.48). The same was true for those who were treated with encapsulated benzoyl peroxide (MD, 4.14, 95 percent CI, 0.62–7.66). [JAMA Dermatol 2026;doi:10.1001/jamadermatol.2026.2062]
Participants treated with either ivermectin or encapsulated benzoyl peroxide were also more likely to achieve Investigator Global Assessment (IGA) success than those who received metronidazole (MDs, 15.51 percentage points and 10.31 percentage points, respectively).
However, treatment discontinuation due to adverse events occurred more frequently with encapsulated benzoyl peroxide than with metronidazole (MD, 8.33, 95 percent CI, 0.45–16.22), primarily driven by application site reactions including pain, erythema, pruritus, and edema.
Limited data precluded synthesis of secondary outcomes, including patient-reported measures and erythema.
Guiding initial therapy selection
“These findings provide comparative evidence to inform initial topical treatment selection but are limited to short-term outcomes,” given that most studies included in the network meta-analysis had a follow-up period of between 8 and 16 weeks, according to the investigators.
“The superior efficacy of ivermectin relative to metronidazole aligns with prior head-to-head trials and systematic reviews, [while] the emergence of encapsulated benzoyl peroxide, which uses microencapsulation technology to prolong drug delivery and potentially minimize irritation, as a highly effective treatment option is noteworthy,” they said.
“When considered alongside its favourable efficacy, ivermectin may be particularly suitable for long-term maintenance therapy. This supports current clinical practice guidelines that recognize ivermectin as a first-line treatment option,” they added. [Br J Dermatol 2019;181:65-79; N Engl J Med 2017;377:1754-1764]
As for encapsulated benzoyl peroxide, the investigators highlighted the need for careful patient selection and counselling regarding potential tolerability issues. “Combining it with strategies to protect the skin barrier may be helpful to improve tolerability.”
Network meta-analysis of trials
The 32 trials involved a total of 11,399 adult patients (mean age 49.4 years) with moderate-to-severe rosacea.
The primary analyses for lesion count and IGA success included only current FDA-approved treatments and dosages. These included metronidazole (0.75% gel, cream, or lotion applied twice daily; 1% gel or cream applied once daily), ivermectin (1% cream applied once daily), minocycline (1.5% foam applied once daily), azelaic acid (15% gel or foam applied twice daily; 20% cream applied twice daily to affected areas), and benzoyl peroxide (5% cream applied once daily).
The investigators acknowledged methodological limitations inherent to the available evidence base, including reliance on indirect comparisons for certain treatments (eg, encapsulated benzoyl peroxide), moderate heterogeneity, and evidence of localized inconsistency within the network.
Also, the trials had relatively short treatment durations, “which may favour agents with a more rapid onset of action,” they added.