A Multicenter Study of Topical Azelaic Acid 15% Gelin Combination With Oral Doxycycline as Initial Therapy and Azelaic Acid 15% as Maintenance Monotherapy
July 2009 | Volume 8 | Issue 7 | Original Article | 639 | Copyright © July 2009
Diane M. Thiboutot MD, Alan B. FleischerMD, James Q. Del Rosso DO,Phoebe Rich MD
This two-phase, multicenter study was undertaken to examine the safety and effi cacy of combination therapy with oral doxycycline
and topical azelaic acid (AzA) 15% gel in moderate-to-severe papulopustular rosacea and to determine the effect of subsequent
maintenance monotherapy with AzA 15% gel alone. In the initial open-label, non-randomized phase of the study, subjects (n=172)
received topical AzA 15% gel and oral doxycycline (100 mg), both twice daily, for ≤ 12 weeks. In the second, double-blind study
phase, subjects who had initially undergone at least four weeks of combination treatment in phase 1 and who achieved ≥75% infl ammatory
lesion count reduction (n=136) were randomized to receive either AzA 15% gel or its vehicle twice daily for an additional 24
weeks. Assessments of effi cacy were obtained at four-week intervals throughout both phases of the study and included change
in infl ammatory lesion count, investigator global assessment (IGA) of rosacea severity, and separate assessments of erythema and
telangiectasia severity. At the last visit for each phase of the study, the investigator and participant each rated overall improvement,
with the participant rating cosmetic acceptability and the investigator rating treatment as “success” or “failure” based on IGA score.
During the second phase of the trial, the rate of relapse—defi ned as either a 50% deterioration in the lesion count improvement from
phase 1, an increase in erythema intolerable to the subject or maintenance therapy failure as judged by the investigator and/or the
subject—was obtained. Safety assessments were conducted for both phases of the study and included analysis of adverse events
(AEs) and a rating of cutaneous tolerability by the subject.
By week 12 of the open-label phase of the study, 81.4% of subjects had reached a 75% or greater reduction in infl ammatory lesion
count, and 64% of patients achieved treatment success. During the second study phase (maintenance phase), AzA 15% gel consistently
provided a better maintenance response than vehicle, with maintenance of remission in 75% of patients over the six-month
duration of the maintenance phase. Additionally AzA 15% gel showed a statistically signifi cantly lower deterioration in absolute
infl ammatory lesion counts than did vehicle after 8, 16, 20 and 24 weeks of maintenance therapy. No serious treatment-related AEs
were encountered in the study, and 98.5% of subjects were satisfi ed with the local tolerability of both AzA gel and vehicle.