Early Acne Improvements With Fixed-Combination Topical Therapy: Analysis of the First 4 Weeks of Treatment

Background: Acne treatment can take weeks to result in noticeable improvements, which may diminish patients’ perception of treatment effectiveness and negatively affect treatment adherence. Acne treatments that deliver early visible improvements may encourage treatment adherence and bolster overall treatment effectiveness. Combination topical treatments that target multiple acne pathophysiological pathways are more efficacious than monotherapies and simplifying the treatment regimen by delivering multiple active ingredients as fixed combinations may improve adherence. Objective: To evaluate early acne improvements in clinical trials of fixed-combination acne topicals. Methods: Week 4 efficacy data for fixed-combination topical treatments were gathered from US Food and Drug Administration medical reviews, prescribing information, and/or publications of pivotal phase 2 and phase 3 clinical trials of 7 acne topicals, comprising fixed combinations of adapalene (ADAP), benzoyl peroxide (BPO), clindamycin phosphate (CLIN), and tretinoin. For the triple-combination formulation (CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel), data from a nonpivotal phase 2 study with dyad combination treatment arms were also included. Outcomes included reductions from baseline in inflammatory lesions (ILs) and noninflammatory lesions (NILs) and treatment success (≥2-grade reduction in global acne severity score and clear/almost clear skin). Results: At week 4, IL reductions from baseline ranged from 32-54% while NIL reductions ranged from 25-45%. Rates of treatment success ranged from 3-12%. Overall, efficacy was greatest with triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel (IL: 54-55%; NIL: 43-45%; treatment success: 8-12%), followed by combinations of ADAP/BPO (IL: ~42-48%; NIL: ~38%; treatment success: 4-~7%). None of the branded topical products were evaluated in a head-to-head study. Conclusions: In pivotal clinical trials of topical fixed-combination formulations for acne, triple-combination CLIN 1.2%/ADAP 0.15%/BPO 3.1% gel yielded greater lesion reductions and rates of treatment success after 4 weeks of treatment than dyad formulations. Even greater differences may be expected with real-world world use, as early improvements may foster better long-term outcomes by increasing patients’ confidence in and adherence to the treatment. Funding: Ortho Dermatologics