Tazarotene versus tazarotene plus clindamycin/benzoyl peroxide in the treatment of acne vulgaris: a multicenter, double-blind, randomized parallel-group trial

Journal of Drugs in Dermatology, March, 2006 by Emil Tanghetti, William Abramovits, Barry Solomon, Keith Loven, Alan Shalita

Abstract

Topical retinoids offer highly effective treatment for both inflammatory and non-inflammatory acne, with tazarotene demonstrating greater efficacy than other topical retinoids. A multicenter, double-blind, randomized, parallel-group trial has been performed to evaluate whether the adjunctive use of clindamycin/benzoyl peroxide could enhance the efficacy of tazarotene still further. Patients with moderate to severe inflammatory acne applied tazarotene 0.1% cream each evening and were randomly assigned to morning applications of vehicle gel or a ready-to-dispense formulation of clindamycin 1%/benzoyl peroxide 5% gel containing 2 emollients. Tazarotene/clindamycin/benzoyl peroxide achieved a significantly greater reduction in comedo count than tazarotene monotherapy and, among patients with a baseline papule plus pustule count of [greater than or equal to]25 (the median value), a significantly greater reduction in inflammatory lesion count. The combination therapy was also at least as well-tolerated as tazarotene monotherapy. The adjunctive use of clindamycin/benzoyl peroxide gel with tazarotene cream promotes greater efficacy and may also enhance tolerability. Any improvements in tolerability could be due to the emollients in the clindamycin/benzoyl peroxide gel formulation.

Introduction

Due to their ability to inhibit the development of microcomedos--which are the precursors of all other acne lesions--topical retinoids such as tazarotene are recommended as first-line therapy not only for most cases of comedonal acne but also for mild to moderate inflammatory acne. (1,2) Topical retinoids are thought to act primarily by helping to normalize abnormal desquamation of follicular epithelium in the infrainfundibular portion of the pilosebaceous unit. This facilitates the drainage of not only comedos but also microcomedos--and thus helps to prevent the subsequent development of both inflammatory and non-inflammatory acne lesions. The comedolytic action of topical retinoids also helps to normalize the follicular microenvironment making it less favorable for the proliferation of Propionibacterium acnes (P. acnes). Furthermore, topical retinoids have been reported to have direct immunomodulatory effects that may also contribute to their efficacy against inflammatory acne lesions--including inhibition of the expression of toll-like receptor 2 (3) and the stimulation of interleukin-5 release and inhibition of interferon-[gamma] release by superantigen-stimulated human peripheral blood mononuclear cells. (4) Finally, by thinning the stratum corneum, topical retinoids may also enhance the follicular penetration of other agents (1,5)--suggesting that they may even help enhance the efficacy of adjunctive therapies used in combination regimens.

Tazarotene has been shown to offer greater efficacy than other topical retinoids. (6-9) However, it may be possible to enhance its efficacy still further through the adjunctive use of other agents that have different mechanisms of action--for example, antibiotics and benzoyl peroxide. These agents primarily have antibacterial and anti-inflammatory activity and it is thought that their antibacterial action also helps limit the release of comedogenic products from P. acnes (5)--benzoyl peroxide in particular has been reported to have comedolytic activity. (1,10,11) As a result, combination antibiotic/benzoyl peroxide products (such as clindamycin/benzoyl peroxide) offer efficacy against both inflammatory and non-inflammatory acne lesions. (12,13) Furthermore, they can also help prevent the development of antibiotic resistance and offer significant clinical improvement among patients who have already developed antibiotic resistance. (11)

With these complementary actions, it might be anticipated that the adjunctive use of clindamycin/benzoyl peroxide with tazarotene treatment could offer greater clinical benefit than tazarotene alone. To investigate this, a multicenter, double-blind, randomized, parallel-group study has been performed.

Methods

Patients

Patients were eligible for enrollment if they were at least 12 years of age and had stable moderate to severe facial inflammatory acne vulgaris (defined as 15-60 papules plus pustules, 10-100 comedos, and no more than 2 nodulocystic lesions with a maximum diameter of 5 mm).

Exclusion criteria included patients with acne known to be resistant to oral antibiotics and females who were pregnant, breastfeeding, or of childbearing potential and not using reliable contraception. In addition, the following washout periods were required: 2 weeks for topical acne medications, 30 days for systemic antibiotics and investigational drugs, 12 weeks for estrogens/birth control pills if previously used for less than 12 weeks, and 6 months for oral retinoids.

Treatment Regimen

All patients were instructed to apply tazarotene 0.1% cream to their face each evening for 12 weeks. In addition, patients were randomly assigned to adjunctive treatment with either vehicle gel or clindamycin 1%/benzoyl peroxide 5% gel (a ready-to-dispense formulation containing 2 emollients) each morning.