Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne: Association of Efficacy With Cutaneous Safety/Tolerability Events

Abstract

Background: Topical treatment of acne—particularly with retinoids—often incurs a transient period of dermal irritation characterized by erythema, scaling, and other dermal changes that may reflect the same mechanisms of action by which acne pathophysiology is addressed. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel demonstrated efficacy in the treatment of acne, with a safety/tolerability profile typical of topical acne treatment. The objective of this post-hoc analysis is to determine whether CAB efficacy was related to occurrence of cutaneous safety/tolerability events.

Methods: Data were pooled from 4 double-blind, 12-week studies of participants with moderate-to-severe acne. Efficacy endpoints included treatment success (percentage of participants achieving ≥2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of 0 or 1 [clear/almost clear]) and reductions from baseline in inflammatory (IL) and noninflammatory lesions (NIL). Cutaneous safety/tolerability assessments of erythema and scaling (investigator-assessed) and itching, burning, and stinging (participant-assessed) were graded on a 4-point scale (0=none, 1=mild, 2=moderate, 3=severe). To determine if CAB efficacy was associated with cutaneous events, efficacy endpoints at week 12 were compared for CAB-treated participants who experienced no increase versus ≥1-grade (any) increase in any safety/tolerability score at weeks 2, 4, or 8.

Results: At week 12, CAB-treated participants experiencing any safety/tolerability event (n=411) had significantly greater rates of treatment success and IL reductions, and numerically greater NIL reductions, than those without events (n=188; treatment success: 55.0% vs 43.0%; P<0.01; IL reductions: 79.1% vs 72.3%; P<0.001; NIL reductions: 73.1% vs 68.1%). At weeks 2, 4, and 8, IL/NIL reductions were significantly greater among participants experiencing any cutaneous event than those without events (P<0.05, all). Overall, improved efficacy appeared to be driven by events of scaling, itching, and burning.   

Conclusions: Across four clinical studies, CAB-treated participants who experienced safety/tolerability events at weeks 2, 4, or 8 also experienced greater lesion reductions across 12 weeks of treatment and greater rates of treatment success at week 12. These findings are consistent with the theory that early instances of cutaneous irritation during topical acne treatment may reflect therapeutic mechanisms of action. Setting patient expectations regarding the potential for transient irritation during treatment may contribute to greater adherence and efficacy with CAB gel. 

Funding: Ortho Dermatologics