Topical retinoids

Philadelphia - Combination therapy with a topical retinoid and oral or systemic antibiotic represents first-line treatment for patients with inflammatory acne, but once adequate clearing is achieved, maintenance therapy with a topical retinoid alone is worth a try, says James J. Leyden, M.D., emeritus professor of dermatology, University of Pennsylvania, Philadelphia.

Expert recommendations

Members of the Global Alliance to Improve Outcomes in Acne (J Am Acad Dermatol 2003;49 (Suppl):S1-37) advocated dual retinoid-antibiotic therapy for treating inflammatory acne. That approach targets multiple mechanisms in acne pathophysiology. It has been demonstrated in controlled clinical trials to afford faster and more complete lesion clearing than monotherapy with either component alone.

Now, however, evidence is available from clinical trials to demonstrate that once antibiotic treatment is stopped, ongoing topical retinoid therapy alone can maintain good acne control in a significant proportion of patients.

"There remains a common misconception that topical retinoids are only beneficial for treating non-inflammatory acne," Dr. Leyden explains. "However, considering that these medications interfere with the development of microcomedones, which are the precursor to comedones and inflammatory lesions, it is not surprising that the retinoids are highly effective agents for managing inflammatory disease.

"Previous studies have demonstrated the efficacy of retinoid monotherapy for reducing counts of comedones, papules and pustules in patients with less severe acne, and now there is evidence from studies of patients with moderate and severe acne to show retinoid monotherapy can be an effective maintenance regimen for preventing inflammatory lesion recurrence even in persons with relatively severe disease."

Evidence-based support

Dr. Leyden was the lead author of a poster presented at the American Academy of Dermatology's Academy '05 in Chicago that summarized the results of an Allergan-sponsored study evaluating tazarotene 0.1 percent gel (Tazorac) as maintenance therapy in patients who were initially treated with combination retinoid-antibiotic therapy. He was also involved as an investigator in a Galderma-sponsored study investigating maintenance monotherapy with adapalene 0.1 percent gel (Differin).

The tazarotene study was a multicenter trial enrolling patients with moderate or severe facial acne. It began with an open-label treatment phase during which all subjects used tazarotene 0.1 percent gel in the evening and took minocycline 100 mg twice daily. Participants who achieved at least 75 percent improvement in the global response to treatment assessment after 12 weeks were eligible for continuation in a 12-week, double-blind, double-dummy maintenance phase comparing tazarotene 0.1 percent gel once daily, minocycline 100 mg twice daily and continued combination therapy.

A total of 110 patients entered the maintenance phase, and the three treatment groups were similar in their baseline demographic characteristics. Outcomes of the maintenance phase were assessed with ratings of overall disease severity, percentages of patients maintaining ≥50 percent and ≥75 percent global improvement, and mean reductions from baseline counts of closed comedones and inflammatory lesions (papules plus pustules).

Between-group comparisons showed no statistically significant differences in the efficacy of the three regimens in any of those measures.

"Some of the patients in this study had relatively severe acne and might be considered candidates for isotretinoin therapy. The results from this trial show that some of these individuals can be adequately treated without resorting to that oral retinoid, and can continue to do well with retinoid monotherapy after initial combination treatment," Dr. Leyden says.

Adapalene stands alone

The adapalene study enrolled 467 patients with moderate to moderately severe acne who began treatment for 12 weeks with adapalene 0.1 percent gel once daily plus doxycycline 100 mg once daily. The majority of patients achieved a 2-grade or greater improvement in the global assessment scale of acne severity and were randomized 1:1 to continue double-blind maintenance treatment with adapalene gel or vehicle.

After 16 weeks, acne control was sustained in 84 percent of patients in the adapalene gel arm, and the difference compared with the vehicle arm was statistically significant.

In both trials, initial combination treatment was well-tolerated, and no new treatment-related adverse events developed during the maintenance study period.