Customized Single-agent Therapy Management of Severe Inflammatory Acne: A Randomized, Double-blind, Parallel-group, Controlled Study of a New Treatment – Adapalene 0.3%-Benzoyl Peroxide 2.5% Gel
December 2015 | Volume 14 | Issue 12 | Original Article | 1427 | Copyright © December 2015
Jonathan Weiss MD,a Linda Stein Gold MD,b Matthew Leoni MD,c Maria Jose Rueda MD,d Hong Liu Msc,c and Emil Tanghetti MDe
a Gwinnett Clinical Research Center Inc., Snellville, GA
b Henry Ford Medical Center, Dept. of Dermatology, Detroit, MI
c Galderma Research and Development, Princeton, NJ
d Galderma Laboratories LP, Fort Worth, TX
e Center for Dermatology and Laser Surgery, Sacramento, CA
Abstract
BACKGROUND: More effective therapies are needed in the specific treatment of severe inflammatory acne vulgaris.
OBJECTIVES: To demonstrate superior efficacy of adapalene 0.3%-benzoyl peroxide 2.5% gel (0.3% A/BPO) vs. vehicle, and to assess efficacy of 0.3% A/BPO vs. 0.1% A/BPO in subjects with severe inflammatory acne (Investigator’s Global Assessment [IGA] of 4) in the context of a larger trial in a moderate and severe population.
METHODS: This was a multicenter, randomized, double-blind, parallel-group, 12-week study. Subjects were randomized to receive 0.3% A/BPO, 0.1% A/BPO (benchmark) or vehicle (comparator) once daily for 12 weeks. Co-primary efficacy endpoints were success rate at week 12 (percentage of subjects rated “clear” or “almost clear,” ≥3-grade IGA improvement), and change in inflammatory (IN) and noninflammatory (NIN) lesion counts from baseline to week 12. Secondary efficacy endpoints were percent changes in IN and NIN lesion counts. Safety endpoints were incidence of adverse events (AEs) and local tolerability signs/symptoms.
RESULTS: In the severe inflammatory acne population, a total of 252 subjects were randomized with 106, 112 and 34 subjects in the 0.3% A/BPO, 0.1% A/BPO and vehicle groups, respectively, reaching a high rate of study completion (88.5%). At week 12, both 0.3% A/BPO and 0.1% A/BPO were superior to vehicle in terms of lesion count reduction. However for success rate, only 0.3% A/BPO achieved significantly greater efficacy over vehicle with a treatment difference of 20.1% (31.9% vs. 11.8%; 95% Confidence Interval (CI): [6.0%, 34.2%],
P=.029), whereas 0.1% A/BPO did not (treatment difference vs. vehicle of 8.8%;
P=.443). This translates to an 11% difference between active treatments in favor of 0.3% A/BPO. Also, 0.3% A/BPO was safe and well tolerated.
CONCLUSIONS: Availability of this new treatment option should allow clinicians to better customize severe inflammatory acne management, and the high-strength product provides a step-up treatment when needed.
J Drugs Dermatol. 2015;14(12):1427-1435.
INTRODUCTION
As a chronic disease, acne is associated with negative psychological effects and can cause scarring from inflammation.
1-2 A recent U.S. population-based study among 9,417 children found that the prevalence of severe acne increased from 11 years (about 2%) to 17 years of age (12%).3 The severity of acne in adolescence is associated with several factors including history of severe acne in first-degree relatives4 and occurrence in boys in early puberty.5
The pathophysiological mechanisms of severe acne are recently becoming better understood. The management of severe acne is complex, and multiple factors, including the safety profile of medications, must be taken into consideration.6 This has driven
further research into alternative medications and devices, including radiofrequency, laser, and light treatments, however, these agents have not demonstrated consistent efficacy and safety.7 Current therapies available in the treatment of severe inflammatory acne are rather limited. Only a few topical agents have been studied in severe inflammatory acne, either alone, including clindamycin 1.2%/BPO 2.5% and 3.75% gel, clindamycin
1.2%/tretinoin 0.025% gel, tazarotene cream and foam 0.1%, and dapsone 5% gel, or in combination with oral antibiotics, such as doxycycline along with adapalene and benzoyl peroxide
(BPO) as a fixed-dose combination gel (hereafter, 0.1% A/BPO, Epiduo® Gel, Galderma Laboratories, L.P.).8-13 However, in Phase III published clinical trials for the previously mentioned topical acne treatments, less than 20% of subjects had severe acne at inclusion.8-11, 14
