Azelaic Acid (AZA)

AZA is a newer therapeutic option for the treatment of rosacea. It was approved by the US FDA in 2002, the European Union in 2003, and in Canada in 2004, although it has only recently become commercially available in Canada. AZA is a naturally occurring dicarboxylic acid that can be found in dietary sources, such as whole grains.[3] It lacks toxicity, is nonteratogenic and nonmutagenic.[4] It has multiple biologic effects including anti-inflammatory, antikeratinizing and antibacterial activities. The likely mechanism of action is via inhibition of reactive oxygen species produced by neutrophils.[4]

A novel 15% gel formulation (Finacea®, Intendis/Bayer) is available for the treatment of rosacea, in addition to a 20% cream formulation approved for use in acne vulgaris. The 15% gel, although formulated to a lower concentration than the cream, is significantly more bioavailable than the cream because of an optimized aqueous gel vehicle. Multiple reviews have been published examining the use of AZA in rosacea.[3,5,6] Two pivotal phase III trials have shown that AZA 15% gel, applied twice daily for 12 weeks, was superior when compared with the vehicle for patients with papulopustular rosacea.[7] A mean reduction in inflammatory lesion counts ranged from 51%–58% in the AZA group, compared with 39%–40% in the vehicle group. Improvement in erythema scores ranged from 44%–46% in patients treated with AZA, compared with 28%–29% in the vehicle group.[7] In a 15-week study, AZA 15% gel applied twice daily also showed significant benefit over metronidazole 0.75% gel.[8] In these studies, the use of AZA 15% gel led to a mean reduction in inflammatory lesion counts ranging from 51%–73% and a reduction of erythema severity ranging from 44%–56%. The number of patients achieving success, as defined by the investigator global assessment, ranged from 61%–69%.[7–9]

A split-face study by Maddin[10] comparing AZA 20% cream with metronidazole 0.75% cream, showed a reduction in inflammatory lesions of 78.5% and 69.4%, respectively. There was also a reduction in erythema of 25.5% and 18.7% for AZA and metronidazole, respectively. Both treatments led to a significant reduction in inflammatory lesions over 15 weeks, but the difference between treatments was not significant.[10] Of note, the physician rating of global improvement was significantly higher on the side treated with AZA at both weeks 9 and 15.[10] In the comparative studies, AZA had a greater potential to cause irritation than the metronidazole, which included facial skin signs and symptoms. However, these events were reported as mild to moderate and transient in nature.[8] There was no improvement reported in telangiectasia severity in any study of AZA for rosacea.

The dosing recommendation for AZA 15% gel is a twice daily application. However, Thiboutot et al. found once daily dosing to be as effective as twice daily.[11] Research has shown that AZA when used as a treatment for papulopustular rosacea is a safe and effective and exhibits a favorable tolerability profile.