Mechanism-based treatment of acne vulgaris: the value of combination therapy

Journal of Drugs in Dermatology, May-June, 2005 by Guy Webster

In a similar study evaluating adapalene gel 0.1% plus the oral tetracycline antibiotic lymecycline (300 mg/day) in 118 patients with moderate inflammatory acne, the combination therapy was significantly more effective than the oral antibiotic alone. Males and females aged 20 to 30 years with moderate to moderately severe acne were enrolled, and patients were required to have a global severity grade ranging from 4 to 10 on the Leeds Revised Acne Grading System, and to have at least 15 inflammatory facial lesions (no more than 3 nodules) and at least 20 non-inflammatory facial lesions. The combination was superior to oral lymecycline alone in reducing total lesion count showing a significant reduction by week 8. The combination was significantly more effective in reducing both non-inflammatory and inflammatory lesions (P = .0519 and P = .0001, respectively). Skin irritation was slightly more common in the adapalene group; however, both treatments were generally well-tolerated with a similar incidence of adverse events. (27)

Finally, a multicenter, investigator-masked, randomized, parallel-group study was performed in 44 patients with mild-to-moderate facial acne to compare the efficacy and tolerability of tazarotene as monotherapy versus 3 combination regimens. The combinations were tazarotene plus benzoyl peroxide gel; tazarotene plus clindamycin phosphate lotion; and tazarotene plus erythromycin/benzoyl peroxide gel. (28) A clindamycin phosphate monotherapy group was included as a reference. All tazarotene-based therapies were significantly more effective than clindamycin monotherapy in reducing non-inflammatory lesions. (28)

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Strategies to Limit Side Effects with Combination Regimens

Using combinations of agents can enhance efficacy, but increase side effects. Therefore, the tolerability of a topical retinoid is important. Strategies to enhance retinoid tolerability include use of the retinoid analog, adapalene, new delivery systems such as the tretinoin microsphere delivery system, or alternative dosing schedules, such as short contact and every other day (QOD) regimens that have been used successfully with tazarotene. (29) In all combination regimens involving topical retinoids and antibiotics, the topical retinoid should be continued after discontinuation of the antibiotic to maintain remission of new acne lesions. (1)

Conclusion

Combination therapy with topical retinoids and oral or topical antibacterial agents address 3 out of 4 pathophysiologic factors underlying the development of acne vulgaris. Such combinations have been proven to have a significantly greater and faster effect on acne lesions without significantly increasing the tolerability burden, and reduce the resistance-inducing potential of antibiotic therapy. The use of combination therapy--either two topical agents or a topical and oral agent--right from the start has the potential to increase patient satisfaction and compliance, and simplify management for the dermatologist.