Drug combination trumps single-agent acne treatment

New Orleans - Combining a popular topical retinoid with a widely used antibiotic - and applying them at the same time as if they were one drug - clearly outperforms using either agent separately in treating acne, according to new data presented at the 63rd Annual Meeting of the American Academy of Dermatology (AAD) here.

The key is adding to them a novel aqueous hydrogel that solubilizes the two old standby drugs and stabilizes them to provide a particularly effective once-daily treatment.

"Chemically, tretinoin and clindamycin are incompatible agents," explains lead investigator James J. Leyden M.D., professor emeritus of dermatology, University of Pennsylvania School of Medicine.

Thus, when combined traditionally, without the hydrogel, separate application regimens are required.

"Our randomized controlled studies are the first to compare clindamycin/ tretinoin hydrogel combined vs. each agent alone and vehicle." In the two poster studies, "we demonstrated the combination's power in treating both inflammatory and non-inflammatory lesions," Dr. Leyden tells Dermatology Times.

He notes that he had suggested the concept of combining a topical retinoid and an antibiotic for acne as far back as 1973 but "not until 2003, when a team of international experts stated in a pivotal report that the combination was the way to go," was his idea accepted. (See J of the American Academy of Dermatology 2003, 49, "Management of Acne: Report of a Global Alliance").

In the meantime, however, clindamycin and tretinoin used separately, became standard acne-fighters, the former for reducing levels of P. acnes and decreasing inflammation, the latter for normalizing follicular keratinization and slowing desquamation.

Study methodology The 12-week studies Dr. Leyden reported at AAD involved 2,219 men and women, 12 years or older with facial inflammatory and non-inflammatory lesions, randomized to either a once-daily application of mixed clindamycin (1 percent)/tretinoin (0.025 percent) hydrogel; or clindamycin (1 percent) hydrogel; or tretinoin (0.025 percent) hydrogel; or vehicle hydrogel.

The researchers collected efficacy and safety data at baseline, and again at weeks two, four, eight and 12.

The results clearly showed the percent reduction in lesions was significantly greater with the combination than with each active factor - including vehicle - alone, Dr. Leyden emphasizes.

For example, "The mean percent reduction in inflammatory lesion counts from baseline to week 12 was 53.4 percent with the combination, compared to 47.5 percent for clindamycin gel, 43.3 percent for tretinoin gel and 30.3 percent for vehicle gel."

The corresponding findings with non-inflammatory lesions were 45.2 percent, 31.6 percent, 37.9 percent and 18.5 percent.

Adds Dr. Leyden: "At the end of treatment, 37 percent of those who received the combination had clear or almost clear skin requiring no further therapy as assessed by a special modernized scoring system (the Investigator's Static Global Assessment (ISGA))."

The three active treatments evaluated in these studies were also found to be well tolerated, with 87.6 percent of subjects showing not even one adverse experience, he says.

"Overall, less than 1.5 percent of participants discontinued treatment due to adverse events - and these were not related to treatment," he says.

The combination product (Velac, Connetics Corporation) is still investigational and being analyzed by the U.S. Food and Drug Administration pending approval anticipated later this year, a spokesperson for the manufacturer tells Dermatology Times.

Dr. Leyden also notes, "Speed is a must with adolescents and young adults - our typical acne patients. They are generally non-compliant with slow-working medications, and the problem with clindamycin and topical tretinoin alone is that, although effective, each must be applied separately, which takes time and discourages the patient..."