Topical Preparations for the Treatment of Mild-to-moderate Acne Vulgaris

Systematic Review and Network Meta-analysis

B. Stuart; E. Maund; C. Wilcox; K. Sridharan; G. Sivaramakrishnan; C. Regas; D. Newell; I. Soulsby; K.F. Tang; A.Y. Finlay; H.C. Bucher; P. Little; A.M. Layton; M. Santer


The British Journal of Dermatology. 2021;185(3):512-525. 

In This Article

Abstract and Introduction


Background: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective.

Objectives: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis.

Methods: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA.

Results: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low.

Conclusions: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.


Acne vulgaris (hereafter 'acne') is very common in both adolescents and adults.[1] Acne can have significant impact on quality of life, including increased risk of depression.[2] Guidelines differ in their recommendations and quality,[3] but National Institute for Health and Care Excellence Clinical Knowledge Summary (NICE CKS) UK guidelines suggest that first-line treatment should be a single-agent topical treatment, followed by combination topical treatment.[4] Guidelines in the USA, Canada and Europe are similar, recommending combination topical treatment as first-line therapy.[5–7] Although topical preparations, such as benzoyl peroxide (BPO) and topical retinoids (e.g. adapalene) can be effective, there is uncertainty regarding the most appropriate strategy for initial and maintenance treatment.[2] While the prescription of topical antibiotics as monotherapy in the UK is declining, topical antibiotics as monotherapy or in combination are still widely prescribed[8] and contribute to antibiotic resistance.[9,10]

A 2014 James Lind Alliance Priority Setting Partnership for acne included the question 'What is the best topical product for treating acne?' in their top 10 priorities for future research.[11] There are multiple topical acne treatments and it is not feasible to review and compare them all. However, it is reasonable to address the question set out in the Priority Setting Partnership by comparing treatments suggested in European guidelines as first-line topical preparations for mild and moderate acne that are prescribed in the UK.

Although these treatments are widely used, there are gaps in the evidence base regarding their effectiveness and tolerability. To date, there have been two Cochrane reviews that have assessed topical treatments for acne.[12,13] However, these reviews were able to provide only limited head-to-head evidence for key treatments, including adapalene + BPO, which are widely used and recommended in guidelines.

The uncertainty in the evidence base regarding optimal choice of topical treatments for acne is important because (i) topical antibiotics, alone or in combination, may be used despite being no more effective than topical nonantibiotic treatments, (ii) uncertainty leads to potential delays in treating acne effectively, and (iii) patients may progress to other treatments if acne does not improve, e.g. long courses of oral antibiotics.

While traditional meta-analysis is limited to direct head-to-head comparisons, network meta-analysis techniques, sometimes also called multiple-treatments meta-analysis, can overcome this by using all available data to build a network of direct and indirect comparisons. It allows estimates of effectiveness of treatment in addition to estimates of incoherence (how well the whole network fits together).[14]