Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha‐hydroxy acid) for acne

Plain language summary Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and fruit acid (alpha‐hydroxy acid) for acne Background Acne vulgaris (‘acne’) is a costly and common skin disorder in which hair follicles become blocked. Acne affects up to 85% of adolescents and young adults. Topical retinoids (treatment derived from vitamin A) and antimicrobials (treatment that kills micro‐organisms such as bacteria) are common treatments. Other topical medications are also used, but there are concerns about their efficacy and safety. Review question This Cochrane Review aimed to assess the effects of six topical treatments (azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha‐hydroxy acid (organic acids found in food, sometimes known as fruit acid) on people with acne when compared with an inactive substance (placebo), no treatment, or other topical treatments. The evidence is current to May 2019. Study characteristics We included 49 trials (3880 reported participants). At least one study assessed each eligible treatment. Most trial participants were female, aged between 12 and 30 years, with mild to moderate acne. Nearly 60% of the trials treated participants for longer than eight weeks. Study duration ranged from three months to three years. Nine trials reported pharmaceutical support. The studies were mainly conducted in Europe, Asia, and the USA, in clinics, hospitals, research centres, and universities. Key results The following results were measured at the end of treatment, which was mainly long term (more than 8 weeks) for the outcome ‘Participants’ global self‐assessment of acne improvement’ (PGA) and mixed in length, but mainly medium term (from 5 to 8 weeks), for ‘Total number of participants who experienced at least one minor side effect’. Azelaic acid probably leads to worse PGA when compared to benzoyl peroxide, but when compared to tretinoin, there is probably little or no difference (both moderate‐quality evidence). When comparing azelaic acid to clindamycin, there may be little or no difference in PGA (low‐quality evidence), but we are uncertain whether azelaic acid reduces PGA compared to adapalene (very low‐quality evidence). In terms of participant withdrawal (for any reason), there may be no difference when azelaic acid is compared with benzoyl peroxide, clindamycin, and tretinoin (all low‐quality evidence). We are uncertain whether azelaic acid reduces withdrawals when compared to adapalene (very low‐quality evidence). We are uncertain whether azelaic acid has fewer total minor adverse events when compared to adapalene or benzoyl peroxide (very‐low quality evidence). When comparing azelaic acid to clindamycin, there may be no difference in total adverse events (low‐quality evidence). The studies that compared azelaic acid with tretinoin only reported individual side effects (e.g. scaling). We are uncertain if there is a difference between salicylic acid and pyruvic acid on PGA score (very low‐quality evidence). There may be little or no difference between salicylic acid and tretinoin in PGA (low‐quality evidence). No study comparing salicylic acid with benzoyl peroxide assessed PGA. There may be no difference in withdrawals when comparing salicylic acid and pyruvic acid; there were no withdrawals when salicylic acid was compared to tretinoin (both low‐quality evidence). We are uncertain if there is a difference in withdrawals between salicylic acid and benzoyl peroxide (very low‐quality evidence). We are uncertain whether salicylic acid reduces total minor adverse events when compared to benzoyl peroxide or tretinoin (very low‐quality evidence). For salicylic acid compared with pyruvic acid only individual application site reactions were reported (e.g. scaling and redness). None of the four studies assessing nicotinamide (compared to clindamycin or erythromycin) assessed PGA. Nicotinamide may make no difference to withdrawals when compared to clindamycin or erythromycin, and may make no difference to total minor adverse events when compared to clindamycin (both low‐quality evidence); however, no studies comparing nicotinamide with erythromycin looked at total minor adverse events. Glycolic acid peels may make no difference to PGA when compared to salicylic‐mandelic acid peels (low‐quality evidence), we are uncertain of the effect on total minor adverse events (very low‐quality evidence), and there were no withdrawals (low‐quality evidence). Quality of the evidence Our evidence quality was mixed for the PGA outcome (very low to moderate), mainly low quality for withdrawals, and very low quality for total minor side effects. We had some concerns with the small size of the studies and how they were conducted.