Comparison of clindamycin/benzoyl peroxide, tretinoin plus clindamycin, and the combination of clindamycin/benzoyl peroxide and tretinoin plus clindamycin in the treatment of acne vulgaris: a randomized, blinded study

Journal of Drugs in Dermatology, Sept-Oct, 2005 by Steven Bowman, Michael Gold, Adnan Nasir, George Vamvakias

Abstract

In the treatment of mild to moderate acne vulgaris, the combination of an antibiotic and benzoyl peroxide provides enhanced efficacy over the individual agents, with the potential to decrease the emergence of resistant strains of P. acnes. To evaluate treatment regimens combining the daily use of a clindamycin/benzoyl peroxide gel, a tretinoin gel, and a clindamycin gel, the current randomized, evaluator-blind study was conducted. Results demonstrate that once-daily administration of clindamycin/benzoyl peroxide gel (combination formulation) was as effective as clindamycin/benzoyl peroxide gel + tretinoin gel + clindamycin gel. Both of these regimens provided greater efficacy than tretinoin + clindamycin. Treatment with clindamycin/benzoyl peroxide demonstrated a significant benefit over other treatments at Week 2, highlighting its rapid onset of action. All regimens were safe and generally well tolerated, with less severe peeling seen in patients who received clindamycin/benzoyl peroxide. In conclusion, the regimens that included clindamycin/benzoyl peroxide were more effective than tretinoin + clindamycin in the treatment of acne vulgaris, with no clinical advantage of adding tretinoin + clindamycin to once-daily clindamycin/benzoyl peroxide treatment.

Introduction

The development of acne vulgaris is caused by follicular hyperproliferation, excessive sebum production, and inflammation, resulting in the obstruction of sebaceous follicles. Propionibacterium acnes proliferates in this environment, producing chemotactic factors and proinflammatory mediators that may result in inflammation. (1) Current therapies include topical or systemic retinoids and antibiotics to control epidermal proliferation/differentiation and proliferation of P. acnes respectively. The majority of patients present with mild to moderate acne vulgaris, with topical therapies the treatment of choice for these patients. In patients with more severe disease, systemic therapies may be required.

Tretinoin was one of the first topical retinoids to be used for the treatment of acne vulgaris. (2) Topical tretinoin normalizes desquamation of the follicular epithelium, promotes drainage of preexisting comedones, and inhibits the formation of new comedones. (3) It has been suggested that tretinoin also increases the accessibility of the follicles to other agents such as antibiotics to control P. acnes proliferation. (3)

Topical antibiotics act predominantly antimicrobially, reducing follicular microbial colonization. They also demonstrate anti-inflammatory activity by suppressing chemotaxis. (4) Although P. acnes is sensitive to a range of antibiotics, the therapeutic value of individual antibiotics is dependent upon the degree to which these compounds are soluble in the lipid-rich environment within acne vulgaris lesions. Topical antibiotics of choice include erythromycin and clindamycin, which have activity against P. acnes and are relatively lipophilic. (5) Clindamycin is the more lipophilic of these antibiotics and may penetrate the acne vulgaris lesion more effectively. (1)

Lipophilic bactericidal agents such as benzoyl peroxide are also effective in reducing P. acnes in vivo and have been used in combination with antibiotics. Not only do such combinations enhance efficacy over the individual agents, they also minimize P. acnes resistance to antibacterials. For example, the combination of clindamycin and benzoyl peroxide has demonstrated significantly greater efficacy than either agent alone, (6-10) including a reduction in the emergence of resistant strains of P. acnes. (6)

Other combination therapies with clindamycin, benzoyl peroxide, and tretinoin may provide further advantages in the treatment of acne vulgaris. However, the use of tretinoin in combination with clindamycin/benzoyl peroxide has not been extensively evaluated. Therefore, a randomized, evaluator-blind, multicenter study was conducted to compare the efficacy and safety of treatment regimens combining the daily use of a clindamycin/benzoyl peroxide gel, a tretinoin gel, and a clindamycin gel in acne vulgaris.

Methods

Study Design

This was a multicenter (3 sites), randomized, evaluator-blind, parallel-group study. The efficacy and safety of the following treatment regimens were compared: once-daily treatment with the combination formulation of clindamycin 1%/benzoyl peroxide 5% gel applied in the morning (Group 1), once-daily treatment with tretinoin 0.025% gel and clindamycin 1% gel applied in the evening (Group 2), and clindamycin 1%/benzoyl peroxide 5% gel applied in the morning plus tretinoin 0.025% gel and clindamycin 1% gel applied in the evening (Group 3).

Inclusion and Exclusion Criteria

Male and female patients between 12 and 30 years of age with a definite clinical diagnosis of acne vulgaris and an Investigator's Global Acne Severity score of 1.5 to 3.0 were included in this study (Table 1). This severity scale was designed to incorporate descriptions based on the Pillsbury classification and includes specific photographs from the Leeds photographic acne scale as references. (11) Photographs were intended to provide an overall impression of acne severity at grades 1, 2, and 3, rather than encompass all criteria for each grade level.