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


This study compared the most commonly prescribed topical treatments for acne in the UK and found no convincing evidence that topical treatments containing antibiotics are more effective in treating acne than those that do not contain antibiotics. Adapalene + BPO appears to be ranked the most effective treatment on all included outcomes. It is also associated with a higher odds of withdrawal owing to adverse events, but the overall incidence of this outcome was low for all treatments.

Systematic reviews to date have not provided direct comparisons of some of the most commonly prescribed treatments. The recently published Cochrane review of BPO did not show statistically significant differences between BPO and other treatments;[12] however, the study was not able to provide estimates for all other treatment comparisons. Similarly, the Cochrane review including azelaic acid[13] was able to draw on only a limited number of direct trials to quantify differences between treatments.

This network analysis benefits from the additional power of indirect comparisons within the network. However, caution is still needed in interpreting these results. Findings presented here help to highlight gaps where further head-to-head trials are needed. The rankings we have reported are sensitive to inclusion criteria and may change as further evidence emerges. Moreover, the confidence in the evidence was low, with considerable uncertainty remaining about the true effect estimate owing to poor reporting of study methods and the substantial number of trials with industry involvement.

The use of oral antibiotics for acne is high[62] and contributes to antibiotic resistance. Whereas resistance to topical antibiotics tends to be limited to the treated site, oral antibiotics can lead to resistance in commensal flora at all body sites.[9] This study suggests that nonantibiotic treatments are effective as first-line treatment. Further research is needed to explore how these treatments compare with oral antibiotics used alone or in combination with topical treatments.

Although we looked at many outcomes that were important to our patient panel, the study was hampered by poor and inconsistent reporting of trial outcomes. For the participant-reported outcome, only 11 trials were included. The other 30 trials either did not report the outcome of interest (n = 26) or it was reported inconsistently between trials (n = 4). Efforts to harmonize the reporting of outcomes is needed, particularly as the outcomes most commonly reported, such as lesion counts, were not the ones that the patient panel felt were most meaningful.

For the purposes of this review, we considered total lesion counts. Members of our patient panel felt that this was more meaningful than the distinction between inflammatory and noninflammatory lesions. However, it is possible that the use of this global outcome disguises changes whereby certain phenotypes respond better to specific treatments.

Data on adverse events were particularly poorly reported and we were not able to assess this outcome. This makes it difficult to discuss relative risks and benefits of the different treatments in a meaningful way. Although we have been able to compare the likelihood of participants discontinuing the study, reasons were rarely reported. We were not able to compare adverse events that may concern patients starting a new treatment regimen, such as stinging, itching or peeling.

Blinding was reported in a number of trials and a suitable vehicle was used. However, BPO or retinoids can cause adverse events such as redness or peeling. This might have led to participants or clinicians guessing the allocation. It is hard to quantify the extent to which this may have occurred as it was not reported but, if this did occur, it would lower the overall quality of the reported evidence.

Transitivity is one of the key assumptions of network meta-analysis. In order to achieve a population that was as homogeneous as possible, we excluded full texts where the reported severity of acne was not clearly mild-to-moderate. Within the scope of the review, we did not have the resources to contact all authors of these excluded full texts to obtain clarification. It is possible that limiting the review in this way may have improved homogeneity but introduced a selection bias. Similarly, we did not have the resources to translate articles from other languages. We found 24 titles and abstracts in other languages that may potentially have been eligible. These represent a small proportion of the total titles and abstracts screened, but the inclusion of only English-language full texts may be a source of bias.

The medications in the network analysis account for about two-thirds of prescriptions in the UK in 2018,[8] but there are notable gaps, with some treatments being poorly connected to the network and comparisons based on only a single trial. Data on azelaic acid were only available for the lesion count outcome and there were limited trials on combinations including erythromycin or erythromycin alone, which comprise a substantial proportion of topical prescriptions alone or in combination with other treatments.[8,63]

We were also unable to investigate different concentrations of included treatments in the scope of this review. The pooling of treatment strength into a single comparison may disguise differences in effectiveness of different formulations and strength and further research is needed to explore this topic. Moreover, ethnicity was too poorly reported to explore whether there were any differences with respect to different skin types or skin colours.

Based on evidence mainly graded as low to very low confidence, all topical treatments were more effective than vehicle, and adapalene + BPO was the most effective. Clinicians should evaluate this treatment option in consultation with patients as, although withdrawal owing to adverse events was uncommon, treatment with adapalene + BPO also appeared to have a slightly higher odds of this outcome. Further work is needed to compare topical treatment with oral antibiotic treatments and to consider which treatments may be most cost-effective.