Efficacy and Safety of Once-Daily Topical Brimonidine Tartrate Gel 0.5% for the Treatment of Moderate to Severe Facial Erythema of Rosacea: Results of Two Randomized, Double-blind, and Vehicle-Controlled Pivotal Studies

June 2013 | Volume 12 | Issue 6 | Original Article | 650 | Copyright © June 2013

Joseph Fowler Jr. MD,a J. Mark Jackson MD,a Angela Moore MD,b Michael Jarratt MD,c Terry Jones MD,d Kappa Meadows MD,e Martin Steinhoff MD,f Diane Rudisill BSc,g and Matthew Leoni MDg on behalf of the Brimonidine Phase III Study Group

aUniversity of Louisville, Louisville, KY bArlington Center for Dermatology, Arlington, TX cDermResearch, Inc, Austin, TX dJ&S Studies, Inc, College Station, TX eThe Education & Research Foundation, Inc, Lynchburg, VA fUniversity of California at San Francisco, San Francisco, CA gGalderma R&D, Princeton, NJ

BACKGROUND: Brimonidine tartrate, a highly selective α2-adrenergic receptor agonist with potent vasoconstrictive activity, was shown to reduce erythema of rosacea.
OBJECTIVE: To assess the efficacy and safety of topical brimonidine tartrate gel 0.5% for the treatment of erythema of rosacea.
METHODS: Both studies were randomized, double-blind, and vehicle-controlled, with identical design. Subjects with moderate to severe erythema of rosacea were randomized 1:1 to apply topical brimonidine tartrate gel 0.5% or vehicle gel once-daily for 4 weeks, followed by a 4-week follow-up phase. Evaluations included severity of erythema based on Clinician’s Erythema Assessment and Patient’s Self-Assessment, as well as adverse events.
RESULTS: Topical brimonidine tartrate gel 0.5% was significantly more efficacious than vehicle gel throughout 12 hours on days 1, 15, and 29, with significant difference observed as early as 30 minutes after the first application on day 1 (all P<.001). No tachyphylaxis, rebound or aggravation of other disease signs were observed. Slightly higher incidence of adverse events was observed for topical brimonidine tartrate gel 0.5% than for vehicle; however, most of the adverse events were dermatological, mild, and transient in nature.
LIMITATIONS: These data generated in controlled trials may be different from those in clinical practice.
CONCLUSIONS: Once-daily brimonidine tartrate gel 0.5% has a good safety profile and provides significantly greater efficacy relative to vehicle gel for the treatment of moderate to severe erythema of rosacea, as early as 30 minutes after application.

J Drugs Dermatol. 2013;12(6):650-656.


Rosacea is a common skin disorder estimated to affect 16 million Americans.1 Although it is usually observed in patients with light skin phototypes, rosacea has also been diagnosed in patients with darker skin type III – VI.2-4 The onset of the condition is typically between the ages of 20-50 years, with women being affected more frequently than men.5 As rosacea is a chronic disease characterized by flushing and persistent erythema in the central facial area,6 it has considerable psychosocial impact and causes embarrassment, anxiety, and low self-esteem among the patients.7, 8 In addition to flushing and erythema, other cutaneous signs such as telangiectasia, papules, and pustules may also be present.9, 10 Several topicaland oral medications are currently approved for the treatment of papules and pustules of rosacea, including metronidazole, azelaic acid, and anti-inflammatory dose doxycycline.11, 12
Although erythema is the primary feature of rosacea and presents ubiquitously among rosacea patients, there is currently no approved medication for its treatment, making it a key unmet medical need.5 In the absence of effective treatment, patients are usually advised to identify and avoid environmental and lifestyle triggers that can exacerbate erythema.11-13 It is hypothesized that facial erythema of rosacea results from dysregulation in the cutaneous vasomotor responses, which leads