Nonantibiotics Most Effective Acne Treatments

girl with acne cream
girl with acne cream
The most effective and best tolerated topical treatments for acne were identified using network meta-analysis.

Added antibiotics were not found to be the most effective treatment for acne; instead, benzoyl peroxide (BPO) plus adapalene was the most effective of all acne treatments analyzed in a meta-analysis published in the British Journal of Dermatology.

Investigators conducted a network meta-analysis of randomized controlled trials from search engine inception until June 2020. Trials were included of patients with mild to moderate acne and trials of patients with mixed acne severity if 50% or fewer patients had severe acne, based on UK or European acne guidelines. Investigators did not exclude trials based on patient age, setting, or previous treatments. Studies on unusual forms of acne or acne related to endocrinopathies were excluded.

Before beginning the study, investigators created a 10-member patient panel for input on how to measure “effectiveness” and “adverse events.” The patient panel strongly recommended including patient-reported acne assessments as that was more important to them than the clinician’s acne assessment.

The analysis compared topical acne treatments available in the UK with placebo/vehicle or other topical treatments included in a list compiled by a panel of dermatologists, general practitioners, and patients. The primary outcomes were the percentages of self-reported moderate or better global acne improvement and patient withdrawal from trials due to adverse events.

There were 81 papers included in the final analysis, encompassing 40 trials and 18,089 patients. The most common treatment studied was BPO vs vehicle. The mean trial sample size was 454 patients (SD, 524), average age was 19.77 (SD, 3-13) years), and 57.7% were girls or women.

BPO plus adapalene was 3.65 times more likely to be effective than vehicle according to patient-reported global improvement assessments (95% CI, 2.58-5.15). BPO plus adapalene was likely significantly more effective than all other treatments included in the analyses except for BPO plus clindamycin (OR, 1.22; 95% CI, 0.81-1.85). BPO plus clindamycin was also significantly more effective than BPO alone (OR, 1.54; 95% CI, 1.14-2.08) or clindamycin alone (OR, 1.91; 95% CI, 1.36-2.68).

According to investigators’ global assessment of 14 trials for acne improvement to “clear” or “almost clear,” all treatments were significantly more effective than vehicle, except for tretinoin. BPO plus adapalene was significantly more effective than all treatments, except for BPO plus clindamycin, with an OR of 3.83 (95% CI, 2.40-6.10) compared with vehicle. According to the pooled network estimate, BPO plus adapalene was about twice as likely to improve acne as BPO or adapalene monotherapy.

There were 35 trials that reported patient withdrawal; the overall number of patients who discontinued due to adverse events was low. Clindamycin alone was associated with the lowest odds of withdrawal, and BPO plus adapalene was associated with the highest odds of withdrawal (OR, 4.35; 95% CI, 2.13-9.09).

The largest change in mean total lesion counts occurred in patients using BPO plus adapalene with a difference of 20.96 lesions (95% CI, -25.02 to -16.90) compared with vehicle, as well as other treatments besides erythromycin plus tretinoin, as the confidence intervals were very wide and the confidence ratings were very low in these studies. BPO plus clindamycin had the second largest difference in mean lesion count. BPO plus clindamycin and BPO monotherapy were more effective than clindamycin monotherapy.

The trials included showed mostly low to very low confidence ratings in comparison grading. This was due to poor reporting of study methods and industry involvement in many of the trials, the study authors believe. Many of the trials did not report outcomes of interest, such as adverse events, consistently or at all. The analysis was also limited to English-language texts.

The study authors recommended that clinicians discuss BPO plus adapalene with their patients, including its higher association with adverse events, as an effective treatment for moderate to severe acne.

They also noted that these results have implications for avoiding antibiotic therapy in acne treatment, which contributes to antibiotic resistance, but more research is still needed comparing topical and oral antibiotic treatments.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


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. Published online April 7, 2021. doi:10.1111/bjd.20080