PMID- 32356369 OWN - NLM STAT- MEDLINE DCOM- 20200911 LR - 20240228 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 5 IP - 5 DP - 2020 May 1 TI - Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha-hydroxy acid) for acne. PG - CD011368 LID - 10.1002/14651858.CD011368.pub2 [doi] LID - CD011368 AB - BACKGROUND: Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear. OBJECTIVES: To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne. SEARCH METHODS: We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. SELECTION CRITERIA: Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. MAIN RESULTS: We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence). AUTHORS' CONCLUSIONS: Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs. CI - Copyright (c) 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Liu, Haibo AU - Liu H AD - Department of Dermatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. FAU - Yu, Haiyan AU - Yu H AD - Department of Dermatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. FAU - Xia, Jun AU - Xia J AD - Nottingham China Health Institute, The University of Nottingham Ningbo, Ningbo, China. FAU - Liu, Ling AU - Liu L AD - Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. FAU - Liu, Guan J AU - Liu GJ AD - Cochrane China, West China Hospital, Sichuan University, Chengdu, China. FAU - Sang, Hong AU - Sang H AD - Department of Dermatology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. FAU - Peinemann, Frank AU - Peinemann F AD - Pediatric Oncology and Hematology, Children's Hospital, University of Cologne, Cologne, Germany. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20200501 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Anti-Bacterial Agents) RN - 0 (Dermatologic Agents) RN - 0 (Dicarboxylic Acids) RN - 0 (Glycolates) RN - 0 (Keratolytic Agents) RN - 0 (Mandelic Acids) RN - 0WT12SX38S (glycolic acid) RN - 1L4806J2QF (Adapalene) RN - 25X51I8RD4 (Niacinamide) RN - 3U02EL437C (Clindamycin) RN - 5688UTC01R (Tretinoin) RN - 63937KV33D (Erythromycin) RN - 70FD1KFU70 (Sulfur) RN - 8558G7RUTR (Pyruvic Acid) RN - F2VW3D43YT (azelaic acid) RN - J41CSQ7QDS (Zinc) RN - NH496X0UJX (mandelic acid) RN - O414PZ4LPZ (Salicylic Acid) RN - W9WZN9A0GM (Benzoyl Peroxide) SB - IM UOF - doi: 10.1002/14651858.CD011368 MH - Acne Vulgaris/*drug therapy MH - Adapalene/adverse effects/therapeutic use MH - Adolescent MH - Adult MH - Anti-Bacterial Agents/therapeutic use MH - Benzoyl Peroxide/therapeutic use MH - Bias MH - Child MH - Clindamycin/adverse effects/therapeutic use MH - Dermatologic Agents/adverse effects/*therapeutic use MH - Dicarboxylic Acids/adverse effects/therapeutic use MH - Erythromycin/adverse effects/therapeutic use MH - Female MH - Glycolates/therapeutic use MH - Humans MH - Keratolytic Agents/therapeutic use MH - Male MH - Mandelic Acids/therapeutic use MH - Niacinamide/adverse effects/therapeutic use MH - Patient Dropouts/statistics & numerical data MH - Pyruvic Acid/adverse effects/therapeutic use MH - Quality of Life MH - Salicylic Acid/therapeutic use MH - Sulfur/therapeutic use MH - Tretinoin/therapeutic use MH - Young Adult MH - Zinc/therapeutic use PMC - PMC7193765 COIS- Haibo Liu: nothing to declare
Haiyan Yu: nothing to declare
Jun Xia: nothing to declare
Ling Liu: nothing to declare
Guan J Liu: nothing to declare
Hong Sang: nothing to declare
Frank Peinemann: nothing to declare
Jerry Tan, clinical referee: advisor, consultant, and/or investigator for Allergan, Almirall, Cipher, Galderma, and Valeant EDAT- 2020/05/02 06:00 MHDA- 2020/09/12 06:00 PMCR- 2021/05/01 CRDT- 2020/05/02 06:00 PHST- 2020/05/02 06:00 [entrez] PHST- 2020/05/02 06:00 [pubmed] PHST- 2020/09/12 06:00 [medline] PHST- 2021/05/01 00:00 [pmc-release] AID - CD011368.pub2 [pii] AID - 10.1002/14651858.CD011368.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2020 May 1;5(5):CD011368. doi: 10.1002/14651858.CD011368.pub2.