Background Acne is a chronic inflammatory and immune-mediated disease of the pilosebaceous unit (the skin structure consisting of a hair follicle and its associated sebaceous gland). It is characterised by non-inflammatory lesions (open and closed comedones) and inflammatory lesions (papules, pustules, nodules, and cysts). Lesions may be present on the face, thorax, and back, with variable severity. Acne exhibits a global distribution and has a growing prevalence. Acne vulgaris is the most common form. Acne gives rise to complications such as scars and can seriously affect people's mental health, especially those with severe acne. Acne has a huge impact on the quality of life and self-esteem of those affected. Objectives To synthesise the existing evidence on the efficacy and safety of non-systemic pharmacological interventions and non-pharmacological interventions (physical therapy and complementary therapies) in the treatment of acne vulgaris and related skin complications. Methods We searched the Cochrane Database of Systematic Reviews, Epistemonikos, MEDLINE, and Embase to 2 December 2021, and checked the reference lists of included reviews. At least two authors were responsible for screening, data extraction, and critical appraisal. We excluded reviews with high risk of bias as assessed with the ROBIS tool. We evaluated the overall certainty of the evidence according to GRADE (as carried out by the authors of the included reviews or ourselves). We provide comprehensive evidence from the review data, including summary of findings tables, summary of results tables, and evidence maps. Main results We retrieved and assessed a total of 733 records; however, only six reviews (five Cochrane reviews and one non-Cochrane review) with low risk of bias met the overview inclusion criteria. The six reviews involved 40,910 people with acne from 275 trials and 1316 people with acne scars from 37 trials. The age of the participants ranged from 10 to 59 years, with an average age range from 9.8 to 30 years. Four reviews included original trials involving only female participants and three reviews included original trials with only male participants. Main results for clinically important comparisons: Benzoyl peroxide versus placebo or no treatment: In two trials involving 1012 participants over 12 weeks, benzoyl peroxide may reduce the total (mean difference (MD) -16.14, 95% confidence interval (CI) -26.51 to -5.78), inflammatory (MD -6.12, 95% CI -11.02 to -1.22), and non-inflammatory lesion counts (MD -9.69, 95% CI -15.08 to -4.29) when compared to placebo (long-term treatment), but the evidence is very uncertain (very low-certainty evidence). Two trials including 1073 participants (time point: 10 and 12 weeks) suggested benzoyl peroxide may have little to no effect in improving participants' global self-assessment compared to placebo (long-term treatment), but the evidence is very uncertain (risk ratio (RR) 1.44, 95% CI 0.94 to 2.22; very low-certainty evidence). Very low-certainty evidence suggested that benzoyl peroxide may improve investigators' global assessment (RR 1.77, 95% CI 1.37 to 2.28; 6 trials, 4110 participants, long-term treatment (12 weeks)) compared to placebo. Thirteen trials including 4287 participants over 10 to 12 weeks suggested benzoyl peroxide may increase the risk of a less serious adverse event compared to placebo (long-term treatment), but the evidence is very uncertain (RR 1.46, 95% CI 1.01 to 2.11; very low-certainty evidence). Benzoyl peroxide versus topical retinoids: Benzoyl peroxide may increase the percentage change in total lesion count compared to adapalene (long-term treatment), but the evidence is very uncertain (MD 10.8, 95% CI 3.38 to 18.22; 1 trial, 205 participants, 12 weeks; very low-certainty evidence). When compared to adapalene, benzoyl peroxide may have little to no effect on the following outcomes (long-term treatment): percentage change in inflammatory lesion counts (MD -7.7, 95% CI -16.46 to 1.06; 1 trial, 142 participants, 11 weeks; very low-certainty evidence), percentage change in non-inflammatory lesion counts (MD -3.9, 95% CI -13.31 to 5.51; 1 trial, 142 participants, 11 weeks; very low-certainty evidence), participant's global self-assessment (RR 0.96, 95% CI 0.86 to 1.06; 4 trials, 1123 participants, 11 to 12 weeks; low-certainty evidence), investigators' global assessment (RR 1.16, 95% CI 0.98 to 1.37; 3 trials, 1965 participants, 12 weeks; low-certainty evidence), and incidence of a less serious adverse event (RR 0.77, 95% CI 0.48 to 1.25, 1573 participants, 5 trials, 11 to 12 weeks; very low-certainty evidence). Benzoyl peroxide versus topical antibiotics: When compared to clindamycin, benzoyl peroxide may have little to no effect on the following outcomes (long-term treatment): total lesion counts (MD -3.50, 95% CI -7.54 to 0.54; 1 trial, 641 participants, 12 weeks; very low-certainty evidence), inflammatory lesion counts (MD -1.20, 95% CI -2.99 to 0.59; 1 trial, 641 participants, 12 weeks; very low-certainty evidence), non-inflammatory lesion counts (MD -2.4, 95% CI -5.3 to 0.5; 1 trial, 641 participants, 12 weeks; very low-certainty evidence), participant's global self-assessment (RR 0.95, 95% CI 0.68 to 1.34; 1 trial, 240 participants, 10 weeks; low-certainty evidence), investigator's global assessment (RR 1.10, 95% CI 0.83 to 1.45; 2 trials, 2277 participants, 12 weeks; very low-certainty evidence), and incidence of a less serious adverse event (RR 1.27, 95% CI 0.98 to 1.64; 5 trials, 2842 participants, 10 to 12 weeks; low-certainty evidence). For these clinically important comparisons, no review collected data for the following outcomes: frequency of participants experiencing at least one serious adverse event or quality of life. No review collected data for the following comparisons: topical antibiotics versus placebo or no treatment, topical retinoids versus placebo or no treatment, or topical retinoids versus topical antibiotics. Authors' conclusions This overview summarises the evidence for topical therapy, phototherapy, and complementary therapy for acne and acne scars. We found no high-certainty evidence for the effects of any therapy included. Randomised controlled trials and systematic reviews related to acne and acne scars had limitations (low methodological quality). We could not summarise the evidence for topical retinoids and topical antibiotics due to insuCicient high-quality systematic reviews. Future research should consider pooled analysis of data on new emerging drugs for acne treatment (e.g. clascoterone) and focus more on acne complications.
