SINT MAARTEN, NETHERLANDS ANTILLES — A combination of doxycycline and metronidazole cleared more inflammatory rosacea lesions and worked faster than metronidazole alone in a randomized controlled trial.
This combination should be considered a first-line treatment for rosacea, according to the efficacy and safety findings that were presented by Dr. Joseph F. Fowler Jr. at the Caribbean Dermatology Symposium.
Previous research suggested that agents with anti-inflammatory activity, including doxycycline or tetracycline and topical metronidazole, are effective for management of rosacea symptoms (Cutis 2004;73:15–18; Skinmed 2003;2:43–47).
Dr. Fowler assessed the safety and efficacy of using 40-mg delayed-release doxycycline capsules (Oracea, Galderma), which is the anti-inflammatory dose of the antibiotic, in combination with metronidazole topical gel 1%.
“I chose metronidazole 1% because it is one of the more established products. … I was able to show both drugs had an effect. But when combining the two, you get much faster and greater improvement,” said Dr. Fowler, clinical professor in the dermatology division, University of Louisville (Ky.).
A total of 36 patients were randomized to combination treatment, and another 36 to an oral placebo and metronidazole gel 1% (monotherapy group). Following baseline assessment, patients were evaluated at weeks 4, 8, and 12, at which time metronidazole therapy was stopped. Patients continued to take oral doxycycline or placebo for another 4 weeks.
The 56 women and 16 men enrolled in the study had a mean age of 48 years. Baseline mean total inflammatory lesion count (papules, pustules, and nodules) was similar between groups—21 in the combination group and 19 in the monotherapy group.
A total of 64 participants completed the study—30 in the combination group and 34 in the monotherapy arm. In all, 4 people withdrew because of adverse events (including 3 in the combination group), 2 people withdrew consent, 1 was removed for a protocol violation, and 1 was lost to follow-up.
The primary outcome, mean change in total inflammatory lesion count, was significantly improved in the combination group. For example, from baseline to week 4, the count decreased by 10 lesions among combination patients versus 3 among monotherapy patients. “The quick onset [of the oral drug] is a critical take-home message,” Dr. Fowler said.
By week 16, the mean reduction in total inflammatory lesions was 13 in the combination group, compared with 7 for the monotherapy group.
Patients in the combination therapy group had greater improvements on investigator global assessment at all time points, including significant differences at weeks 12 and 16.
Between weeks 12 and 16, patients who received doxycycline monotherapy maintained the benefits of decreased inflammatory lesion counts and improvements on global assessment.
Dr. Fowler was a consultant and clinical research investigator for CollaGenex Pharmaceuticals Inc. at the time of the study.
Galderma has since acquired CollaGenex, and Dr. Fowler receives research support from Galderma.
By week 4, lesion count decreased by 10 among combination patients and by 3 in those on monotherapy. DR. FOWLER