Review question
We reviewed the evidence showing effects and safety of topical benzoyl peroxide (BPO), used alone or in combination. Eligible comparisons included placebo (an identical but inactive treatment), no treatment, or other active (medical) topical medications for treating acne (used alone or in combination with other topical drugs not containing BPO) (evidence is current to February 2019).
The main outcomes of interest in this review were participant-reported acne improvement and withdrawal from the study due to any side effects. More generally, we also considered the percentage of participants experiencing any side effects over the whole course of a trial.
Background
As a common skin disease, acne vulgaris affects the physical, mental, and social well-being of millions of adolescents and young adults. A wide range of treatments for acne vulgaris are available, and topical BPO has been recommended as a priority therapy to be used alone or combined with other topical or oral treatments, depending on acne severity. However, the benefits and harms of BPO have yet to be evaluated.
Study characteristics
We included 120 studies (which comprised 29,592 people randomised in 116 trials; in four trials the number of randomised participants was unclear). Through our search, we found studies assessing different concentrations of BPO, BPO delivered through various means, or BPO used alone or given with other treatments that may or may not be considered as the primary treatment. These studies compared treatments against different concentrations or formulations of BPO, placebo, no treatment, or other medical treatments given alone or in combination.
Most of the studies included male and female participants with mild to moderate acne; only 67% of studies reported participant age, which ranged between 18 and 30 years. Participants were treated for over eight weeks in nearly two-thirds of the trials. Industry financially supported approximately two-fifths of the trials, and more than half of the trials did not report their funding sources. Few studies reported where they were set, but locations included hospitals, medical centres, national medical institutes, clinics, medical departments, and general practices.
Key results
We found low-certainty evidence to suggest that long-term (i.e. given for longer than eight weeks) BPO treatment may increase self-reported treatment success compared to placebo or no BPO treatment (three studies), but there may be little to no difference when BPO treatment is compared to adapalene (five studies) or clindamycin (one study). This outcome was not reported by studies comparing BPO treatment to erythromycin or salicylic acid.
Long-term BPO may lead to an increased chance of treatment discontinuation compared to placebo or no treatment (24 studies), with the most common causes being redness, itch, and skin burning (low-certainty evidence). When medium- to long-term BPO was compared to adapalene (11 studies), clindamycin (eight studies), erythromycin (one study), or salicylic acid (one study), we found only very low-certainty evidence, meaning that although there may be little to no difference in withdrawal between these groups, we are not sure of the results. It should be noted that participant withdrawal may be linked to issues around treatment acceptability (dermatitis, rash, facial swelling, sensitivity) rather than to safety.
Very low-certainty evidence means that we are uncertain if BPO leads to more side effects among participants receiving medium- to long-term BPO than among those given no treatment/placebo (21 studies), adapalene (seven studies), erythromycin (one study), or salicylic acid (one study). Medium-term treatment with BPO may lead to increased risk of side effects when compared against clindamycin, but the effects of this treatment vary, so the treatment chosen may make little to no difference (six studies; moderate-certainty evidence). Side effects reported in these studies were usually mild to moderate, and the most common were local dryness, irritation, eczema, redness, pain at the site of application, and pruritus.
Certainty of the evidence
For our key comparisons, we rated the certainty of evidence for 'participant-reported acne improvement' as low. For the outcomes 'withdrawal due to adverse effects' and ‘percentage of participants having any adverse events', the evidence was mainly of very low certainty.
Included trials were at high or unclear risk of bias, participant numbers were small, results were not consistent across trials, and we suspected publication bias.
Current evidence suggests that BPO as monotherapy or add-on treatment may be more effective than placebo or no treatment for improving acne, and there may be little to no difference between BPO and either adapalene or clindamycin. Our key efficacy evidence is based on participant self-assessment; trials of BPO versus erythromycin or salicylic acid did not report this outcome.
For adverse effects, the evidence is very uncertain regarding BPO compared with adapalene, erythromycin, or salicylic acid. However, risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment. Withdrawal may be linked to tolerability rather than to safety. Risk of mild to moderate adverse events may be higher with BPO compared with clindamycin.
Further trials should assess the comparative effects of different preparations or concentrations of BPO and combination BPO versus monotherapy. These trials should fully assess and report adverse effects and patient-reported outcomes measured on a standardised scale.
Acne is a common, economically burdensome condition that can cause psychological harm and, potentially, scarring. Topical benzoyl peroxide (BPO) is a widely used acne treatment; however, its efficacy and safety have not been clearly evaluated.
To assess the effects of BPO for acne.
We searched the following databases up to February 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of relevant randomised controlled trials (RCTs) and systematic reviews.
We included RCTs that compared topical BPO used alone (including different formulations and concentrations of BPO) or as part of combination treatment against placebo, no treatment, or other active topical medications for clinically diagnosed acne (used alone or in combination with other topical drugs not containing BPO) on the face or trunk.
We used standard methodological procedures as expected by Cochrane. Primary outcome measures were 'participant global self-assessment of acne improvement' and 'withdrawal due to adverse events in the whole course of a trial'. 'Percentage of participants experiencing any adverse event in the whole course of a trial' was a key secondary outcome.
We included 120 trials (29,592 participants randomised in 116 trials; in four trials the number of randomised participants was unclear). Ninety-one studies included males and females. When reported, 72 trials included participants with mild to moderate acne, 26 included participants with severe acne, and the mean age of participants ranged from 18 to 30 years.
Our included trials assessed BPO as monotherapy, as add-on treatment, or combined with other active treatments, as well as BPO of different concentrations and BPO delivered through different vehicles. Comparators included different concentrations or formulations of BPO, placebo, no treatment, or other active treatments given alone or combined. Treatment duration in 80 trials was longer than eight weeks and was only up to 12 weeks in 108 trials. Industry funded 50 trials; 63 trials did not report funding. We commonly found high or unclear risk of performance, detection, or attrition bias. Trial setting was under-reported but included hospitals, medical centres/departments, clinics, general practices, and student health centres. We reported on outcomes assessed at the end of treatment, and we classified treatment periods as short-term (two to four weeks), medium-term (five to eight weeks), or long-term (longer than eight weeks).
For 'participant-reported acne improvement', BPO may be more effective than placebo or no treatment (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.12 to 1.45; 3 RCTs; 2234 participants; treatment for 10 to 12 weeks; low-certainty evidence). Based on low-certainty evidence, there may be little to no difference between BPO and adapalene (RR 0.99, 95% CI 0.90 to 1.10; 5 RCTs; 1472 participants; treatment for 11 to 12 weeks) or between BPO and clindamycin (RR 0.95, 95% CI 0.68 to 1.34; 1 RCT; 240 participants; treatment for 10 weeks) (outcome not reported for BPO versus erythromycin or salicylic acid).
For 'withdrawal due to adverse effects', risk of treatment discontinuation may be higher with BPO compared with placebo or no treatment (RR 2.13, 95% CI 1.55 to 2.93; 24 RCTs; 13,744 participants; treatment for 10 to 12 weeks; low-certainty evidence); the most common causes of withdrawal were erythema, pruritus, and skin burning. Only very low-certainty evidence was available for the following comparisons: BPO versus adapalene (RR 1.85, 95% CI 0.94 to 3.64; 11 RCTs; 3295 participants; treatment for 11 to 24 weeks; causes of withdrawal not clear), BPO versus clindamycin (RR 1.93, 95% CI 0.90 to 4.11; 8 RCTs; 3330 participants; treatment for 10 to 12 weeks; causes of withdrawal included local hypersensitivity, pruritus, erythema, face oedema, rash, and skin burning), erythromycin (RR 1.00, 95% CI 0.07 to 15.26; 1 RCT; 60 participants; treatment for 8 weeks; withdrawal due to dermatitis), and salicylic acid (no participants had adverse event-related withdrawal; 1 RCT; 59 participants; treatment for 12 weeks). There may be little to no difference between these groups in terms of withdrawal; however, we are unsure of the results because the evidence is of very low certainty.
For 'proportion of participants experiencing any adverse event', very low-certainty evidence leaves us uncertain about whether BPO increased adverse events when compared with placebo or no treatment (RR 1.40, 95% CI 1.15 to 1.70; 21 RCTs; 11,028 participants; treatment for 10 to 12 weeks), with adapalene (RR 0.71, 95% CI 0.50 to 1.00; 7 RCTs; 2120 participants; treatment for 11 to 24 weeks), with erythromycin (no participants reported any adverse events; 1 RCT; 89 participants; treatment for 10 weeks), or with salicylic acid (RR 4.77, 95% CI 0.24 to 93.67; 1 RCT; 41 participants; treatment for 6 weeks). Moderate-certainty evidence shows that the risk of adverse events may be increased for BPO versus clindamycin (RR 1.24, 95% CI 0.97 to 1.58; 6 RCTs; 3018 participants; treatment for 10 to 12 weeks); however, the 95% CI indicates that BPO might make little to no difference. Most reported adverse events were mild to moderate, and local dryness, irritation, dermatitis, erythema, application site pain, and pruritus were the most common.