The relative efficacies of emerging topical acne treatments were outlined in systematic review data published in the Journal of Evidence Based Medicine. Azelaic acid appeared to have comparable efficacy to tretinoin but performed worse than benzoyl peroxide in the long term. Azelaic acid was supported by moderate-quality data, and studies examining salicylic acid, nicotinamide, sulfur, zinc, and fruit acid had greater risk for bias and/or data imprecision. Further high-quality investigation of topical acne treatments is necessary to confirm the effects of these topical agents.

Investigators searched The Cochrane Skin Group Specialized Register, CENTRAL, Embase, and LILACS from inception through May 2019 for randomized controlled trials reporting the efficacy and safety of topical acne treatments. Eligible trials enrolled patients with acne vulgaris of any severity but excluded those with other forms of acne or acneiform eruptions. Topical treatments of interest included azelaic acid, salicylicacid, nicotinamide, sulfur, zinc, and alpha-hydroxy acid. The primary outcomes were participants’ global self-assessment of acne improvement (PGA) and withdrawal from treatment for any reason. In pooled analyses, risk ratios (RRs) were used to summarize effect estimates. Study eligibility and extracted data were independently assessed by 2 review authors. Evidence quality was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool, which took into account study limitations, effect consistency, imprecision, indirectness, and risk for publication bias. 

The review included data from 49 studies published from 1969 to 2017. The pooled study cohort included 3880 patients, most of whom were between the ages of 12 and 30 years. Acne severity typically ranged from mild to moderate. Treatment duration ranged from 5 days to 12 months; more than half of studies used a treatment cycle lasting for 8 weeks or more. A total of 7 trials reported the efficacy of azelaic acid compared with other topical treatments. In long-term trials (treatment duration >8 weeks), azelaic acid 15% gel had worse PGA compared with benzoyl peroxide 5% gel (RR, 0.82; 95% confidence interval [CI], 0.72-0.95). Little to no difference in PGA was observed between azelaic acid 15% gel and tretinoin (RR, 0.94; 95% CI, 0.78-1.14), suggesting comparable efficacy. The data on azelaic acid were of moderate quality per the GRADE tool.  

There were 2 trials that compared salicylic acid with other topical treatments using PGA. In the long term (>8 weeks), salicylic acid 3% lotion had similar PGA outcomes to tretinoin 0.05% cream (RR, 1.00; 95% CI 0.92-1.09). Salicylic acid 30% peels were not significantly different from pyruvic acid 50% peels in the medium term (5-8 weeks) (RR, 1.12; 95% CI, 0.68-1.84). However, studies assessing salicylic acid efficacy were of low to very low quality on the GRADE tool.  

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No studies used PGA to evaluate the efficacy of nicotinamide. Glycolic acid had similar PGA performance compared with salicylic-mandelic acid in the long term (RR, 1.06; 95% CI, 0.88-1.26), although the supporting studies had low quality evidence. Evidence was inconclusive regarding the effects of sulfur and zinc. Across all trials, adverse events with topical treatment were mild and transient.

Results from this abridged Cochrane review highlight the low-quality evidence base surrounding topical acne treatments. Less than half of studies used PGA as an outcome measure. Many studies had low to very low evidence quality, with high risk for attrition or publication bias. The strongest evidence was available for azelaic acid, which performed worse than benzoyl peroxide and comparably to tretinoin. “The risk of bias and imprecision compromise our confidence in the evidence…[W]e are unable to draw definitive conclusions about these topical treatments,” investigators wrote. “We encourage trials with robust methodological quality and standardized reporting…[to] substantially improve the work in this area.”


Liu H, Yu H, Xia J, et al. Evidence-based topical treatments (azelaic acid, salicylic acid, nicotinamide, sulfur, zinc, and fruit acid) for acne: an abridged version of a Cochrane systematic review [published online October 9, 2020]. J Evid Based Med. doi: 10.1111/jebm.12411