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Am Fam Physician. 2022;105(6):online

Clinical Question

What is the best topical treatment for patients with mild to moderate acne vulgaris?

Bottom Line

For patients with mild to moderate acne, this network meta-analysis suggests starting with adapalene/benzoyl peroxide (Epiduo), clindamycin plus benzoyl peroxide (Neuac), or adapalene (Differin) alone. Patients who do not tolerate either combination containing benzoyl peroxide are likely to tolerate adapalene alone. (Level of Evidence = 1a)


An interdisciplinary team of U.K. researchers began by asking patients with acne what was most important to them in a study of acne treatments. The patients stated that self-reported improvement was more important than investigator-reported outcomes. Thus, the primary outcomes of this study were the proportion of patients who reported moderate or better improvement, and the proportion who withdrew from the study or stopped using the medication due to adverse events. This network meta-analysis identified 40 randomized trials evaluating 12 topical agents or topical combinations in 18,089 patients; 79% of the studies were from North America or Europe. Only studies that reported acne severity, and in which fewer than one-half of patients had severe acne, were included. The studies were a mix of an active drug vs. vehicle cream, or an active drug vs. a different active drug. A network meta-analysis reports a meta-analysis of direct comparisons and a meta-analysis of direct and indirect comparisons. 

The authors found that adapalene plus benzoyl peroxide was the most effective compared with vehicle cream based on meta-analyses of both direct and indirect comparisons (odds ratio [OR] = 3.65; 95% CI, 2.58 to 5.15), clindamycin plus benzoyl peroxide coming in second (OR = 2.98; 95% CI, 2.22 to 4.01), and adapalene alone, third (OR = 2.44; 95% CI, 1.66 to 3.60). Limiting the analysis to studies that only made a direct comparison with vehicle cream had similar findings (coherence), which gives greater confidence in the overall results. Adapalene plus benzoyl peroxide had the highest rate of withdrawals due to adverse events (OR = 2.93; 95% CI, 1.69 to 5.08), followed by benzoyl peroxide alone (OR = 1.59; 95% CI, 0.98 to 2.57) and clindamycin plus benzoyl peroxide (OR = 1.44; 95% CI, 0.75 to 2.72). Although absolute probabilities and numbers needed to treat or harm are not reported, the researchers state that withdrawals due to adverse events were uncommon. 

Study design: Meta-analysis (randomized controlled trials) 

Funding source: Government 

Setting: Outpatient (any) 

Reference: Stuart B, Maund E, Wilcox C, et al. Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis. Br J Dermatol. 2021;185(3):512–525.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.
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POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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