New Orleans — Results of a multicenter phase 3, randomized, double-blind, placebo-controlled trial demonstrate the safety and efficacy of a subantimicrobial-dose (SD) of doxycycline for the treatment of rosacea, said Diane M. Thiboutot, M.D., at the 63rd Annual Meeting of the American Academy of Dermatology here.
The study was sponsored by CollaGenex Pharmaceuticals and enrolled 134 adults with moderate-to-severe rosacea who were equally randomized to treatment with placebo or doxycycline 20 mg (Periostat, CollaGenex) twice daily for 16 weeks. In endpoint analyses using the last observation carried forward, SD doxycycline was significantly favored in assessments of mean changes in lesion counts, overall disease severity, and rates of complete clearing (P ≤ 0.014 for all comparisons). In addition, SD doxycycline had an early statistically significant benefit for reducing erythema (P = 0.006) and showed a trend for greater efficacy for improving redness compared with placebo in the endpoint analysis (P = 0.082). Safety of SD doxycycline was excellent as types and incidences of adverse events were similar in the two study groups.
"Rosacea is a chronic disease that can be difficult to treat and often requires long-term use of antibiotics," says Dr. Thiboutot, professor of dermatology, Pennsylvania State University College of Medicine, Hershey. "SD doxycycline provides potent anti-inflammatory effects, and the results of this study show it can be used effectively to improve moderate to severe rosacea without the safety concerns that accompany use of conventional antimicrobial doses."
The patients in the doxycycline group and placebo group had similar mean ages (44.5 and 48.9 years, respectively). The majority of patients in both groups were Caucasian (~90 percent) and female. However, the proportion of females was much higher in the SD doxycycline vs. placebo group (80.6 percent vs. 59.7 percent, respectively.)
Improvement scores Follow-up visits were conducted after three, six, 12 and 16 weeks, and across those visits there was a continued decrease in mean total inflammatory lesion counts (papules, pustules, nodules) among patients treated with SD doxycycline. At week three, total inflammatory lesion counts were reduced by a mean of 3.7 lesions in the SD doxycycline group and 2.7 lesions in the controls. Corresponding values at endpoint for those respective treatment groups were 6.7 and 3.8 (P = 0.009).
"The progressive improvement in lesion counts seen consistently at every time point in this study suggests there may be further benefit gained with continued treatment with SD doxycycline," Dr. Thiboutot says. "Longer term studies would be needed to confirm that concept, although there is evidence of increasing benefit with extended duration of treatment of rosacea using topical agents." Mean reductions in erythema assessment scores were consistently greater in the SD doxycycline group compared with placebo throughout the study, although a statistically significant difference was observed only at week three (mean changes SD doxycycline -1.7; placebo -0.5). In the endpoint analysis, the mean reduction in erythema assessment score was -3.0 in the SD doxycycline group and -2.0 in the placebo group (P = 0.082).
Study conclusion At study conclusion, complete disease clearing was achieved by 13.1 percent of patients treated with SD doxycycline compared with only 1.5 percent of controls (P = 0.014).
The safety analyses showed adverse events were reported by 56.7 percent of patients receiving SD doxycycline and 64.2 percent of the controls. Two patients receiving SD doxycycline and one placebo-treated patient discontinued study participation because of an adverse event.