Interventions for acne scars

Rania Abdel Hay, Khalid Shalaby, Hesham Zaher, Vanessa Hafez, Ching-Chi Chi, Sandra Dimitri, Ashraf F Nabhan, Alison M Layton, Rania Abdel Hay, Khalid Shalaby, Hesham Zaher, Vanessa Hafez, Ching-Chi Chi, Sandra Dimitri, Ashraf F Nabhan, Alison M Layton

Abstract

Background: Acne scarring is a frequent complication of acne and resulting scars may negatively impact on an affected person's psychosocial and physical well-being. Although a wide range of interventions have been proposed, there is a lack of high-quality evidence on treatments for acne scars to better inform patients and their healthcare providers about the most effective and safe methods of managing this condition. This review aimed to examine treatments for atrophic and hypertrophic acne scars, but we have concentrated on facial atrophic scarring.

Objectives: To assess the effects of interventions for treating acne scars.

Search methods: We searched the following databases up to November 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2015, Issue 10), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five trials registers, and checked the reference lists of included studies and relevant reviews for further references to randomised controlled trials.

Selection criteria: We include randomised controlled trials (RCTs) which allocated participants (whether split-face or parallel arms) to any active intervention (or a combination) for treating acne scars. We excluded studies dealing only or mostly with keloid scars.

Data collection and analysis: Three review authors independently extracted data from each of the studies included in this review and evaluated the risks of bias. We resolved disagreements by discussion and arbitration supported by a method expert as required. Our primary outcomes were participant-reported scar improvement and any adverse effects serious enough to cause participants to withdraw from the study.

Main results: We included 24 trials with 789 adult participants aged 18 years or older. Twenty trials enrolled men and women, three trials enrolled only women and one trial enrolled only men. We judged eight studies to be at low risk of bias for both sequence generation and allocation concealment. With regard to blinding we judged 17 studies to be at high risk of performance bias, because the participants and dermatologists were not blinded to the treatments administered or received; however, we judged all 24 trials to be at a low risk of detection bias for outcome assessment. We evaluated 14 comparisons of seven interventions and four combinations of interventions. Nine studies provided no usable data on our outcomes and did not contribute further to this review's results.For our outcome 'Participant-reported scar improvement' in one study fractional laser was more effective in producing scar improvement than non-fractional non-ablative laser at week 24 (risk ratio (RR) 4.00, 95% confidence interval (CI) 1.25 to 12.84; n = 64; very low-quality evidence); fractional laser showed comparable scar improvement to fractional radiofrequency in one study at week eight (RR 0.78, 95% CI 0.36 to 1.68; n = 40; very low-quality evidence) and was comparable to combined chemical peeling with skin needling in a different study at week 48 (RR 1.00, 95% CI 0.60 to 1.67; n = 26; very low-quality evidence). In a further study chemical peeling showed comparable scar improvement to combined chemical peeling with skin needling at week 32 (RR 1.24, 95% CI 0.87 to 1.75; n = 20; very low-quality evidence). Chemical peeling in one study showed comparable scar improvement to skin needling at week four (RR 1.13, 95% CI 0.69 to 1.83; n = 27; very low-quality evidence). In another study, injectable fillers provided better scar improvement compared to placebo at week 24 (RR 1.84, 95% CI 1.31 to 2.59; n = 147 moderate-quality evidence).For our outcome 'Serious adverse effects' in one study chemical peeling was not tolerable in 7/43 (16%) participants (RR 5.45, 95% CI 0.33 to 90.14; n = 58; very low-quality evidence).For our secondary outcome 'Participant-reported short-term adverse events', all participants reported pain in the following studies: in one study comparing fractional laser to non-fractional non-ablative laser (RR 1.00, 95% CI 0.94 to 1.06; n = 64; very low-quality evidence); in another study comparing fractional laser to combined peeling plus needling (RR 1.00, 95% CI 0.86 to 1.16; n = 25; very low-quality evidence); in a study comparing chemical peeling plus needling to chemical peeling (RR 1.00, 95% CI 0.83 to 1.20; n = 20; very low-quality evidence); in a study comparing chemical peeling to skin needling (RR 1.00, 95% CI 0.87 to 1.15; n = 27; very low-quality evidence); and also in a study comparing injectable filler and placebo (RR 1.03, 95% CI 0.10 to 11.10; n = 147; low-quality evidence).For our outcome 'Investigator-assessed short-term adverse events', fractional laser (6/32) was associated with a reduced risk of hyperpigmentation than non-fractional non-ablative laser (10/32) in one study (RR 0.60, 95% CI 0.25 to 1.45; n = 64; very low-quality evidence); chemical peeling was associated with increased risk of hyperpigmentation (6/12) compared to skin needling (0/15) in one study (RR 16.00, 95% CI 0.99 to 258.36; n = 27; low-quality evidence). There was no difference in the reported adverse events with injectable filler (17/97) compared to placebo (13/50) (RR 0.67, 95% CI 0.36 to 1.27; n = 147; low-quality evidence).

Authors' conclusions: There is a lack of high-quality evidence about the effects of different interventions for treating acne scars because of poor methodology, underpowered studies, lack of standardised improvement assessments, and different baseline variables.There is moderate-quality evidence that injectable filler might be effective for treating atrophic acne scars; however, no studies have assessed long-term effects, the longest follow-up being 48 weeks in one study only. Other studies included active comparators, but in the absence of studies that establish efficacy compared to placebo or sham interventions, it is possible that finding no evidence of difference between two active treatments could mean that neither approach works. The results of this review do not provide support for the first-line use of any intervention in the treatment of acne scars.Although our aim was to identify important gaps for further primary research, it might be that placebo and or sham trials are needed to establish whether any of the active treatments produce meaningful patient benefits over the long term.

Conflict of interest statement

Rania Abdel Hay has been involved in the following included studies for this Cochrane review. She was not involved in 'Risk of bias' assessment, or data extraction and analysis of these studies: Leheta 2011, Leheta 2014a, and Leheta 2014b. Khalid Shalaby: nothing to declare. Hesham Zaher: nothing to declare. Vanessa Hafez: nothing to declare. Ching‐Chi Chi: nothing to declare. Sandra Dimitri: nothing to declare. Ashraf Nabhan: Over the last 12 months, Novartis provided honoraria to speak at educational events (content: Designing clinical research). Alison Layton: "Over the last three years, the following companies have invited advice, supported educational events, provided unrestricted research grants, or I have acted as Clinical Investigator (CI)/Principle Investigator (PI) for their clinical trials. Galderma: 1. PI for two clinical trials; 2. CI for peer‐reviewed basic science research study provided with an unrestricted educational grant; 3. member of Global and European Acne panels sponsored by Galderma with unrestricted educational grants; 4. honoraria provided to speak at educational events (unrestricted content); and 5. honoraria provided for consultancy fees as a member of a drug‐monitoring committee. GlaxoSmithKline: consultancy fee for supporting the development of a trial protocol. MEDA: honorarium for speaking at educational symposium (content unrestricted). LeoPharma: PI in a clinical trial. Pfizer: PI in a clinical study. Novartis: PI in a clinical study. L'Oreal: consultancy fee for monitoring a clinical study. I am not affiliated to or hold shares in any one specific company. I will not be involved in the rating and data extraction of any of these studies for this Cochrane review."

Hywel Williams, Cochrane Dermatology Editor: "I work for the NIHR Health Technology Assessment (HTA), which is funding part of this work."