National report — A recent trial comparing two products containing clindamycin, benzoyl peroxide (BPO) and tretinoin found that the combination including a clindamycin/BPO gel provided quicker onset of action than a combination including a BPO wash, the study's author says. The gel product's quicker onset likely will improve patient compliance, he adds.

With many combination products now available for acne treatment, it's important to compare the safety and efficacy of various products, says Leon Kircik, M.D., clinical associate professor of dermatology, Indiana University School of Medicine, and medical director of DermResearch, P.L.L.C., Louisville, Ky.

To that end, Dr. Kircik and three colleagues initiated a multicenter, investigator-blinded, randomized study to compare the safety and efficacy of once-daily combination therapy with benzoyl peroxide 5 percent/clindamycin 1 percent topical gel (BPO/C; Duac, Stiefel) and tretinoin microsphere 0.04 percent gel (TMG) versus clindamycin phosphate 1.2 percent/tretinoin 0.025 percent gel (CPT; Ziana, Medicis) plus a 5 percent BPO wash.

They enrolled 147 subjects with moderate to severe facial acne vulgaris for the 12-week study, which included patient visits performed at baseline and weeks 4, 8 and 12. Investigators randomized patients into two treatment groups. Group 1 (73 subjects) applied BPO/C gel in the morning and TMG 0.04 percent gel each evening. Group 2 (74 subjects) applied BPO 5 percent wash in the morning and CPT gel each evening.

The majority of subjects were female, and around 44 percent in each group were Caucasian.

To assess efficacy, investigators determined each subject's percentage reduction in inflammatory lesions. Secondary efficacy endpoints included investigator global assessment (IGA) on a six-point scale where 0 = clear skin and five = very severe acne.

Researchers used a similar seven-point scale to assess overall disease severity. Additionally, they assessed safety throughout the study by monitoring adverse events. Subjects, on the other hand, evaluated their skin discomfort level using a scale from negative 3 (very uncomfortable) to plus 3 (very comfortable). They also reported their compliance levels and how frequently they used moisturizers (an indicator of local treatment tolerance) during the study period. To account for all moisturizer use, investigators also factored in subjects' sunscreen use.

Ultimately, 84.4 percent of subjects completed the study. However, investigators calculated results based on the intent-to-treat population of 147.

Although IGAs were similar in Groups 1 and 2 at baseline, by week 4, investigators noted a significantly more rapid response in Group 1. More specifically, patients in this group achieved a mean percentage change in IGA from baseline of negative 0.45 (plus or minus 0.53) versus negative 0.31 (plus or minus 0.55) in Group 2 (P=0.0487).

By week 12, however, inter-group differences were not statistically significant: Group 1 achieved a mean IGA change from baseline of negative 1.03 (plus or minus 0.76), versus negative 0.94 (plus or minus 0.92) in Group 2.

Similar patterns emerged with respect to investigator papule counts. By week 4, subjects in Group 1 achieved a mean papule change of negative 44.11 versus negative 26.21 in Group 2 (P= 0.0094). However, intergroup differences in papule counts were not statistically significant at weeks 8 and 12. In contrast, mean pustule counts revealed significant improvement in Group 1 (from 9.45 to 3.6) at week eight, compared to a decline from 11.58 to 6.10 in Group 2 (P= 0.0386), Dr. Kircik says.

Regarding total lesion counts, Group 1 achieved a 36.26 percent reduction from baseline to week 4, versus a 25.26 percent decline in Group 2 (P= 0.0123). At week 8, a significantly greater percentage of subjects in Group 1 (19 percent) showed at least a 75 percent decrease from baseline versus Group 2 (6.9 percent; P= 0.345). By week 12, overall lesion counts for inflammatory and noninflammatory lesions were similar for both groups.

"Both products showed similar efficacy by week 12. But IGAs showed that there was significantly more rapid improvement in Group 1,&$34 Dr. Kircik says.

This is important, because many patients will change treatments and perhaps doctors if they see no results within about a month, he says.

However, he says, "If you can show some improvement early on, this will increase patients' faith in you as a physician, as well as in your treatment. Early onset of action will increase compliance, and compliance indirectly will increase efficacy."

Compliance levels

Throughout the study, patients in both groups reported virtually identical compliance levels (mostly to very compliant), perhaps because they knew they were participating in an academic study, Dr. Kircik says.

Subjects also reported comparable levels of skin comfort, which were all but identical by week 12 (1.88 versus 1.85).

Dr. Kircik says it was somewhat surprising that although both products contained the same basic ingredients, the combination of BPO/C plus TMG gel yielded faster efficacy.

"In topical treatments," he says, "vehicles really do matter. A moisturizing vehicle will decrease irritation and increase the treatment's tolerability."

As for study weaknesses, Dr. Kircik says it was impossible to reach statistical significance with only 147 subjects.

However, doing such a study on a larger scale would be cost-prohibitive, he says. DT

Disclosures: James Q. Del Rosso, D.O., Steven Grekin, D.O., and David Rodriguez, M.D., also served as investigators on this study, which was sponsored by Stiefel.

Dr. Kircik is an investigator for Stiefel, Galderma, OrthoNeutrogena, Medicis and Allergan.