Optimizing Topical Combination Therapy for the Treatment of Acne Vulgaris

March 2012 | Volume 11 | Issue 3 | Original Article | 313 | Copyright © March 2012

Given the multifactorial and complex contributors to acne development, combination therapy is standard of care. By addressing multiple pathogenic factors, combination therapy provides a quicker and more efficacious treatment outcome than monotherapy. Topical retinoids normalize follicular keratinocyte differentiation and are anti-inflammatory. Their use is limited by the potential for cutaneous irritation. Antimicrobials reduce Propionibacterium acnes colonization on the skin and reduce the bacteria's proinflammatory effects. Topical antibiotics and benzoyl peroxide (BPO) are commonly employed in fixed-dose combination products or two separate medications. BPO has the added benefit of being comedolytic and can minimize the risk for bacterial antibiotic resistance. Like topical retinoids, BPO may cause skin irritation, burning, erythema, and peeling. Managing cutaneous side effects when using multiple products that cause irritation can be a challenge. Careful product selection, dose titration, and patient-directed regimens can help to optimize outcomes. This review presents the latest data on two topical acne products that have demonstrated excellent efficacy and tolerability profiles. In addition, their in vitro profiles suggest the potential for combination use, affording greater dosing flexibility.

J Drugs Dermatol. 2012;11(3):313-317.
Acne vulgaris is a chronic disease of the pilosebacous unit that presents with cutaneous comedones, papules, pustules, and nodules of varying severity. Early intervention is the key to avoid permanent scarring. Optimal treatment strategies continue to evolve along with a greater understanding of the pathogenesis of acne.1 Current consensus guidelines recommend the use of combination therapy, simultaneously targeting multiple pathogenic factors.2 The combination of a topical retinoid plus an antimicrobial and a benzoyl peroxide (BPO) product is first-line therapy for most patients with acne.3 A rapid improvement may lead to greater patient adherence, less antibiotic exposure, and lower Propionibacterium acnes (P. acnes) resistance.3 Moreover, early intervention with an efficacious combination therapy can prevent scarring and postinflammatory hyperpigmentation.4
Topical retinoids are recommended as part of first-line therapy for most cases of acne, as well as for maintenance therapy.3 Retinoids influence cellular differentiation and proliferation and normalize abnormal follicular desquamation.5,6 Normalization of keratinization helps to inhibit the formation of microcomedones.7 Furthermore, retinoids have been shown to reduce inflammation through a number of pathways, including downregulating toll-like receptors,8 cytokines,9 and nitric oxide.10 However, topical retinoids are irritating to the skin and commonly cause dryness, erythema, and burning/stinging.11 Irritation, especially during the first few weeks of treatment, can be a limiting factor for treatment adherence in many patients.12 For sensitive patients, it is recommended to start at a low strength and increase as needed to minimize the potential for irritation.13
Antimicrobial treatments, including topical antibiotics and BPO, reduce skin colonization of P. acnes and its subsequent proinflammatory effects. In the 1980s, clindamycin and erythromycin were found to be equally effective in the reduction of acne lesions.14 However, concern about resistant forms of P. acnes has limited the use of antibiotics. BPO reduces the number of P. acnes by suppressing growth15,16 without the risk for resistance selection; thus, it is used in combination with topical antibiotics to prevent development of resistance.17-19 Moreover, the combination of BPO with a topical antibiotic has been shown to be a more effective therapy for acne than either as monotherapy.20 Like topical retinoids, BPO can cause skin irritation, peeling, dryness, and erythema.21
The optimal acne regimen offers patients quick, efficacious results, maximizing patient satisfaction and reducing the risk for scarring.22 Since two of the most commonly used acne medications (retinoids and BPO) are potentially irritating, their