Accelerated Onset of Action and Increased Tolerability in Treating Acne With a Fixed-Dose Combination Gel

February 2016 | Volume 15 | Issue 2 | Original Article | 231 | Copyright © February 2016

Adam Friedman MD,a Kim Waite BSc,b Staci Brandt PA-C MBA MSMR, c and Matthew H. Meckfessel PhDb

aGeorge Washington University, New York, NY
bGalderma Laboratories, L.P. Fort Worth, TX
cSpirig Galderma, Egerkingen, Switzerland

Abstract
Nonadherence to topical acne therapies is a major contributing factor to poor treatment outcomes. Multiple contributing factors have been identified, including a lack of perceived efficacy and fear of side effects. A fixed-dose combination gel of adapalene/benzoyl peroxide gel, 0.1%/2.5% (A-BPO) is an efficacious and safe treatment for a range of acne severities in patients as young as 9 years old. A meta-analysis of 14 clinical studies involving A-BPO was conducted to assess the 4 week efficacy and overall tolerability of this treatment. Over 2,300 subjects were included in the analysis. Mean total, inflammatory, and non-inflammatory lesion counts decreased at 4 weeks by 40.8%, 46.2%, and 37.5%, respectively. Worst post-baseline tolerability scores for stinging/burning, dryness, scaling, and erythema were none or mild for a majority of subjects. The result of this meta-analysis add to the body of literature supporting the use of A-BPO in a variety of acne patients and shows that A-BPO provides meaningful clinical results within 4 weeks and will be well-tolerated for a majority of patients. With a demonstrable quick onset of action and high tolerability, A-BPO may improve adherence, and ultimately treatment outcomes, by addressing factors that contribute to nonadherence.

J Drugs Dermatol. 2016;15(2):231-236.

INTRODUCTION

Adherence to topical acne therapies in dermatology is relatively low with a reported mean adherence to non-isotretinoin treatments at just 35%, ultimately resulting in poor patient outcomes.1 As a result, unnecessary additional visits or exposure to higher doses as well as other medications altogether may follow serving as a source of continued patient frustration, economic burden, and potential risk to the patient.2 Multiple factors have been reported to contribute to nonadherence including lack of perceived efficacy, fear of side effects, difficulty incorporating the treatment routine, and costs of treatment.3,4 Adherence to topical medications is complex and is influenced by patient-physician relationships, patient education, and the medications themselves.5
While successful adherence to topical medications is multifactorial, topical medications that provide a quicker onset of action and are well tolerated, addressing two of these issues, may help to improve adherence and ultimately treatment outcomes. Data on a fixed-dose combination of adapalene/benzoyl peroxide gel, 0.1%/2.5% (A-BPO) demonstrated that this formulation is safe and effective throughout a range of acne severities and in patients as young as 9 years old.6-10 While assessments during these studies were made at multiple time points up to 12 weeks, the overall impact across the studies early in treatment was not elucidated. Therefore, we conducted a meta-analysis of 14 clinical studies using A-BPO to assess the 4-week efficacy and overall tolerability.

METHODS

Data were pooled from 14 clinical studies for the meta-analysis and data from these studies that contained a vehicle control arm were pooled and assessed. Lesion counts were summarized at each visit. The change from baseline was calculated as post-baseline count minus baseline count so that a negative change from baseline represented an improvement. Subjects who did not have inflammatory lesions at baseline were excluded from the percent change calculations for inflammatory lesions. Frequencies and percentages were calculated for investigator global assessment (IGA) scores (scale of 0 [clear] to 4 [very severe]).
Tolerability assessments were assessed by the investigator, which included dryness, erythema, scaling, and stinging/burning, and assessed on 4 point scales of none to severe. Frequencies and percentages of each tolerability assessment were calculated at each study visit and the worst post-baseline scores were summarized. If no post-baseline data existed for a subject, then the worst post-baseline data was set equal to the baseline values.
Not all studies included all measurements. Within each study protocol, the last observation carried forward was performed for missing efficacy data according to the visit schedule in the protocol. If a protocol had no scheduled visit at week 4, then no imputations were performed at week 4. Therefore, the number of subjects at each study visit varied in the meta-analysis. No