A Systematic Review and Network Meta-analysis of Topical Pharmacological, Oral Pharmacological, Physical and Combined Treatments for Acne Vulgaris

Ifigeneia Mavranezouli; Caitlin H. Daly; Nicky J. Welton; Shalmali Deshpande; Laura Berg; Nathan Bromham; Stephanie Arnold; David M. Phillippo; Jane Wilcock; Jingyuan Xu; Jane C. Ravenscroft; Damian Wood; Mohammed Rafiq; Linyun Fou; Katharina Dworzynski; Eugene Healy

Disclosures

The British Journal of Dermatology. 2022;187(5):639-649. 

In This Article

Abstract and Introduction

Abstract

Background: Various treatments for acne vulgaris exist, but little is known about their comparative effectiveness in relation to acne severity.

Objectives: To identify best treatments for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features.

Methods: We undertook a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing topical pharmacological, oral pharmacological, physical and combined treatments for mild-to-moderate and moderate-to-severe acne, published up to May 2020. Outcomes included percentage change in total lesion count from baseline, treatment discontinuation for any reason, and discontinuation owing to side-effects. Risk of bias was assessed using the Cochrane risk-of-bias tool and bias adjustment models. Effects for treatments with ≥ 50 observations each compared with placebo are reported below.

Results: We included 179 RCTs with approximately 35 000 observations across 49 treatment classes. For mild-to-moderate acne, the most effective options for each treatment type were as follows: topical pharmacological – combined retinoid with benzoyl peroxide (BPO) [mean difference 26·16%, 95% credible interval (CrI) 16·75–35·36%]; physical – chemical peels, e.g. salicylic or mandelic acid (39·70%, 95% CrI 12·54–66·78%) and photochemical therapy (combined blue/red light) (35·36%, 95% CrI 17·75–53·08%). Oral pharmacological treatments (e.g. antibiotics, hormonal contraceptives) did not appear to be effective after bias adjustment. BPO and topical retinoids were less well tolerated than placebo. For moderate-to-severe acne, the most effective options for each treatment type were as follows: topical pharmacological – combined retinoid with lincosamide (clindamycin) (44·43%, 95% CrI 29·20–60·02%); oral pharmacological – isotretinoin of total cumulative dose ≥ 120 mg kg−1 per single course (58·09%, 95% CrI 36·99–79·29%); physical – photodynamic therapy (light therapy enhanced by a photosensitizing chemical) (40·45%, 95% CrI 26·17–54·11%); combined – BPO with topical retinoid and oral tetracycline (43·53%, 95% CrI 29·49–57·70%). Topical retinoids and oral tetracyclines were less well tolerated than placebo. The quality of included RCTs was moderate to very low, with evidence of inconsistency between direct and indirect evidence. Uncertainty in findings was high, in particular for chemical peels, photochemical therapy and photodynamic therapy. However, conclusions were robust to potential bias in the evidence.

Conclusions: Topical pharmacological treatment combinations, chemical peels and photochemical therapy were most effective for mild-to-moderate acne. Topical pharmacological treatment combinations, oral antibiotics combined with topical pharmacological treatments, oral isotretinoin and photodynamic therapy were most effective for moderate-to-severe acne. Further research is warranted for chemical peels, photochemical therapy and photodynamic therapy for which evidence was more limited.

Introduction

Acne vulgaris is the eighth most common disease globally, affecting over 0·5 billion people.[1,2] Acne can have a detrimental physical, psychological and social impact.[3,4] Acne severity may be determined by clinical presentation (number and type of lesions), secondary sequelae (scarring, pigmentation), and its psychological and social impact on the patient.[5] Uncertainty around acne treatment effectiveness may be a barrier to treatment.[6] Various topical, oral and physical acne treatments are available, but little is known about their comparative effectiveness, especially in relation to acne severity.

Network meta-analysis (NMA) allows simultaneous estimation of relative effects for any number of treatments, even if some have not been directly compared in randomized controlled trials (RCTs), provided that treatments create a 'network of evidence' where every treatment is linked to at least another treatment through direct comparisons.[7–10]

Two NMAs assessing the effectiveness of treatments for acne vulgaris have been published to date, both focusing on mild-to-moderate acne.[11,12] Therefore, our study examined the relative effectiveness, acceptability and tolerability of topical pharmacological, oral pharmacological, physical and combined treatments separately for mild-to-moderate and moderate-to-severe acne, as determined by clinician-assessed morphological features, to identify suitable first-line treatments.

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