Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the Second REVEAL Trial
March 2018 | Volume 17 | Issue 3 | Original Article | 290 | Copyright © March 2018
Leslie Baumann MD,a David J. Goldberg MD,b Linda Stein Gold MD,c Emil A. Tanghetti MD,d Edward Lain MD,e Joely Kaufman MD,f Emily Weng ScD MBA,g David R. Berk MD,g and Gurpreet Ahluwalia PhDg
aBaumann Cosmetic & Research Institute, Inc, Miami, FL bSkin Laser & Surgery Specialists of NY & NJ, New York, NY cHenry Ford Health System, West Bloomfield, MI dCenter for Dermatology & Laser Surgery, Sacramento, CA eAustin Institute for Clinical Research, Pflugerville, TX fSkin Associates & Skin Research Institute, Coral Gables, FL gAllergan plc, Irvine, CA
Abstract
Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.
J Drugs Dermatol. 2018;17(3):290-298.
INTRODUCTION
Rosacea is a chronic dermatologic condition, marked by persistent facial erythema, flushing, telangiectasia, and inflammatory papules or pustules that affects an estimated 16 million adults in the United States.1,2 If not treated effectively, rosacea can adversely affect quality of life and cause embarrassment, social anxiety, and depression.3 The facial erythema found in rosacea has 2 main components, a persistent macular erythema that tends to be most pronounced on the mid face, and a transient, perilesional erythema that surrounds individual papules and pustules when these lesions are present.4 Pharmacological agents commonly used to treat rosacea can ameliorate inflammatory lesions and perilesional erythema, but provide no benefit for persistent facial erythema.5 Regulation of the cutaneous vasculature is mediated primarily by the sympathetic nervous system, which includes multiple adrenoceptor subtypes.4 Activation of α1- and α2-adrenoceptors on smooth muscle cells produces vasoconstriction of cutaneous blood vessels; consequently, agonists at these receptors have been investigated clinically in rosacea.4,6 Two products are approved by the US Food and Drug Administration for the treatment of adults with persistent facial erythema of rosacea: oxymetazoline hydrochloride cream 1.0% (Rhofade™, Allergan plc, Dublin, Ireland), an α1A-adrenoceptor agonist resulting in vasoconstriction of the cutaneous microvasculature,7 and brimonidine topical gel 0.33% (Mirvaso®, Galderma Laboratories, Fort Worth, TX), a selective α2-adrenoceptor agonist.8,9
