Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis
April 2024 | Volume 23 | Issue 4 | 216 | Copyright © April 2024
Published online March 27, 2024
Julie C. Harper MDa, Hilary Baldwin MDb,c, Saswata Paul Choudhury MSd, Deepti Rai MSd, Bikramaditya Ghosh MPHd, Md Sohai Aman MSd, Abhra R. Choudhury MDSd, Sekhar Kumar Dutta MSd, Debalina Dey MSd, Subrata Bhattacharyya MSd, Tina Lin PharmDe, George Joseph PhDe*, Ankur A. Dashputre PhD MSe, Jerry K.L. Tan MD FRCPCf,g
aThe Dermatology and Skin Care Center of Birmingham, AL
bRobert Wood Johnson Medical Center, New Brunswick, NJ
cThe Acne Treatment and Research Center, Brooklyn, NY
dPharmaQuant, Kolkata, West Bengal, India
eBausch Health US, LLC, Bridgewater, NJ
fWindsor Clinical Research Inc, Windsor, ON, Canada
gDepartment of Medicine, University of Western Ontario, Windsor, ON, Canada
*Current affiliation: BioNTech US Inc, Cambridge, MA
Abstract
Background: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined.
Methods: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and "clear" or "almost clear" for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.
Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle).
Conclusions: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne.
J Drugs Dermatol. 2024;23(4):216-226. doi:10.36849/JDD.8148
INTRODUCTION
Acne vulgaris (acne) is an inflammatory cutaneous disorder of the pilosebaceous unit of the skin that leads to the development of whiteheads, blackheads, papules, pustules, nodules, and cystic lesions.1 It is the most commonly diagnosed skin condition in the United States (US), predominantly among adolescents and young adults in their twenties.1,2 The estimated prevalence in the US is 30.2 per 1,000 people, with more than 8 million cases.3 Annual direct medical costs of acne in the US in 2013 were $846 million and the opportunity costs were $398 million.4
Guidelines from the US, Canada, and Europe recommend topical combination treatments, with consideration of oral drugs, as the first-line approach in moderate-to-severe acne.5-8 Topical benzoyl peroxide (BPO), topical retinoids, topical antibiotics, and systemic drugs are all effective, but there is a lack of clarity about the most efficacious acne treatment.9 Four systematic literature reviews (SLRs) and network meta-analyses (NMAs) have examined the relative efficacy of the numerous acne treatments.8,10-12 Two were specific to patients with mild-to-moderate acne,10,11 and the other 2 included patients with any severity of acne.8,12 No SLR/NMA has specifically addressed patients with
