Acne research pushes for new combinations, probes isotretinoin's secrets

Drugs that combine antibiotics with retinoids are the focus of much research following the approval of Ziana (Medicis), a combination of clindamycin 1.2 percent and tretinoin 0.025 percent, available in a once-a-day gel formation, according to Diane Thiboutot, M.D., professor of dermatology, Penn State College of Medicine, Hershey, Pa.

The drug received Food and Drug Administration (FDA) approval in November 2006 for once-daily topical treatment of acne in patients 12 years and older.

Data from three 12-week, prospective, multicenter, randomized clinical studies showed the combination gel to be more effective than clindamycin or tretinoin alone for achieving clear or almost clear status, as well as for reducing inflammatory and noninflammatory lesion counts.

The FDA reported the most common side effects in the trials included:

The gel is contraindicated in patients with regional enteritis, ulcerative colitis or a history of antibiotic-associated colitis.

Another combination being studied pairs adapalene (Differin, Galderma) with benzoyl peroxide. This combination targets Propionibacterium acnes, follicular hyperkeratinization and inflammation associated with acne, and studies are also looking at a stronger formula of adapalene.

Dr. Thiboutot and other investigators conducted a randomized, multicenter, phase 3 clinical trial looking at a 0.3 percent formula of adapalene, compared with the current 0.1 percent formula on the market.

In that study, 653 patients were randomized to receive adapalene gel 0.3 percent over adapalene gel 0.1 percent or a placebo once daily for 12 weeks.

Results showed that adapalene gel 0.3 percent was significantly superior to adapalene gel 0.1 percent in success rate, total lesion count and inflammatory lesion count. Signs and symptoms were mostly mild-to-moderate and transitory in nature (J Am Acad Dermatol. 2006 Feb;54 (2):242-250).

"A consistent, dose-dependent effect was demonstrated for all efficacy measures," the researchers write.

Clinical trials in recent years also show promise for several treatments that take the approach of specifically targeting inflammation in acne.

A new topical gel form of dapsone, for instance, is gaining notice as a potential treatment that has minimal systemic absorption.

"Dapsone has been around for a while, but there is a novel formulation in which the dapsone is delivered specifically to the skin, where it acts as an anti-inflammatory agent," Dr. Thiboutot tells Dermatology Times.

Two recent randomized studies looked at the safety and efficacy of the gel and found the treatment to be well-tolerated, effective and relatively fast-acting.

In the identically designed, 12-week, double-blind studies, patients aged 12 and older (N = 3010) received twice-daily monotherapy with dapsone gel 5 percent versus a vehicle gel (J Am Acad Dermatol. 2007 Mar;56(3):439.e1-10. Epub 2007 Jan 17).

Patients receiving the dapsone gel showed superior results on a global acne assessment scale, including inflammatory lesion counts. In addition, the reductions in inflammatory lesion counts among patients using dapsone gel were apparent as early as two weeks into the study and reached statistical significance by four weeks.

The researchers report that "no clinically significant changes in laboratory parameters, including hemoglobin, even among glucose-6- phosphate dehydrogenase-deficient patients, were observed."