Prevention and Reduction of Atrophic Acne Scars with Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel in Subjects with Moderate or Severe Facial Acne: Results of a 6-Month Randomized, Vehicle-Controlled Trial Using Intra-Individual Comparison

Abstract

Background: Very few clinical trials have investigated the effect of topical acne treatment on scarring.

Objectives: Our objective was to evaluate the efficacy of adapalene 0.3%/benzoyl peroxide 2.5% gel (A0.3/BPO2.5) in atrophic acne scar formation in patients with acne.

Methods: In this multicenter, randomized, investigator-blinded, vehicle-controlled study, subjects with moderate or severe facial acne (Investigator's Global Assessment [IGA] score 3 or 4; ≥ 25 inflammatory lesions; ten or more atrophic acne scars) applied A0.3/BPO2.5 or vehicle daily per half face for 24 weeks. Subjects with acne requiring systemic treatment were excluded. Assessments included investigator atrophic acne scar count, Scar Global Assessment (SGA), acne lesion count, IGA, skin roughness and skin texture, subject self-assessment of clinical acne-related scars and satisfaction questionnaire, tolerability, and safety.

Results: Included subjects (n = 67) had mainly moderate acne (92.5% IGA 3); mean scores at baseline were approximately 40 acne lesions and 12 scars per half face. By week 24, the change from baseline in total scar count was - 15.5% for A0.3/BPO2.5 versus + 14.4% for vehicle (approximately 30% difference), with a mean of 9.5 scars versus 13.3 per half face, respectively (p < 0.0001). For SGA at week 24, a total of 32.9% with A0.3/BPO2.5 versus 16.4% with vehicle (p < 0.01) were clear/almost clear. Inflammatory acne lesions decreased by 86.7% for A0.3/BPO2.5 versus 57.9% for vehicle (p < 0.0001), and 64.2 versus 19.4% of subjects, respectively, were IGA clear/almost clear (p < 0.0001) at week 24. Treatment-related AEs were reported by 20.9% for A0.3/BPO2.5 versus 9% for vehicle side, most commonly skin irritation (14.9 vs. 6%, respectively).

Conclusions: Topical A0.3/BPO2.5 prevented and reduced atrophic scar formation. Scar count increased with vehicle (+ 14.4%) but decreased with A0.3/BPO2.5 (- 15.5%) over 24 weeks.

Trial registry: ClinicalTrials.gov identifier NCT02735421.

Conflict of interest statement

Funding

This study was funded by Galderma R&D/Nestle Skin Health. Open access was funded by Galderma R&D/Nestle Skin Health.

Conflict of interest

The investigators (JT, RB, AGH, BB, CL, BD) received financial support for conducting the study. Dr. B. Dréno has been an investigator and/or consultant for Bioderma, Galderma, Pierre Fabre, and La Roche Posay. Dr. R. Bissonnette has been an investigator, consultant, advisory board member, and speaker for BioPharmX, Cipher, Dermira, Galderma, GSK-Stiefel, Valeant, and Xenon and is a shareholder of Innovaderm Research. Dr. A. Gagné-Henley has been an investigator, consultant, advisory board member, and/or speaker for Abbvie, Celgene, Dignity, Galderma, Janssen, Leo pharma, Novartis, Sanofi, Valeant, and Xenon. Dr. B. Barankin has been a consultant and speaker for Galderma. Dr. C. Lynde has been a consultant, advisory board member, and speaker for Bayer, Galderma, GSK, and Valeant. Dr. J. Tan has been an investigator, consultant, advisory board member, and speaker, and has provided expert testimony, for Galderma. Mr N. Kerrouche is an employee of Galderma R&D.

Ethical approval

This study was conducted in accordance with the principles of the Declaration of Helsinki and in compliance with the International Conference on Harmonization-Good Clinical Practice and local regulatory requirements. The study was reviewed and approved by the appropriate Independent Ethics Committees, and written informed consent was obtained from all subjects prior to study initiation. Additional informed consent was obtained from all individual participants whose photographs are included in this article.

Figures

Fig. 1

Effect on scars demonstrated by a total atrophic scar count at week 24, b mean percentage change from baseline of total atrophic scar count by visit (ITT; N = 67), and c percentage of subjects with Scar Global Assessment clear/almost clear by visit (ITT; N = 67). A0.3/BPO2.5 adapalene 0.3%/benzoyl peroxide 2.5% gel, ITT intention to treat, LOCF last observation carried forward, PP per protocol

Fig. 2

Effect on lesions expressed as median percentage change from baseline in a total, b inflammatory, and c non-inflammatory lesion count (each result is for half a face) (intention-to-treat population; N =67). A0.3/BPO2.5 adapalene 0.3%/benzoyl peroxide 2.5% gel

Fig. 3

Percentage of subjects clear/almost clear of acne lesions on Investigator Global Assessment (intention-to-treat population; N =67)

Fig. 4

Representative photographs of two subjects who applied adapalene 0.3%/benzoyl peroxide 2.5% gel on the right side of their face and vehicle on the left side. a An 18-year-old subject with Scar Global Assessment (SGA) scores of mild on both sides at baseline (scar count: eight scars A0.3/BPO2.5 vs. five vehicle) and, at week 24, mild SGA on the A0.3/BPO2.5 side (11 scars) and moderate SGA on the vehicle side (16 scars). b A 16-year-old subject with moderate SGA on both sides at baseline (scar count: 32 scars on each side) and moderate SGA on both sides at week 24 (27 scars A0.3/BPO2.5 side vs. 29 scars vehicle side)

Fig. 5

Subject questionnaire. When looking at the left/right hand side of your face in the mirror right now, a “How many indents or holes do you see?” (b) “How visible are the indents or holes to you?” (intention-to-treat population). A03/BPO2.5 adapalene 0.3%/benzoyl peroxide 2.5% gel

Fig. 6

Local tolerance stinging/burning score between baseline (N = 66) and week 24 (N =54) (all patients treated population). A03/BPO2.5 adapalene 0.3%/benzoyl peroxide 2.5% gel