Real-World Efficacy of Azelaic Acid 15% Gel for the Reduction of Inflammatory Lesions of Rosacea

Paul J. Wirth, MD; Meagan-Helen Henderson Berg; Neil Sadick, MD, FAAD, FAACS, FACP, FACPh

Disclosures

Skin Therapy Letter. 2017;22(6):5-7. 

In This Article

Abstract and Introduction

Abstract

Approximately 16 million Americans have rosacea, an inflammatory cutaneous disorder with central facial erythema, papules, pustules, telangiectasia, flushing, and swelling being among the more commonly recognized features. Overexpression of cathelicidin peptide LL-37 has been implicated in the pathophysiology of rosacea. Azelaic acid has been found to inhibit the pathologic expression of cathelicidin, as well as the hyperactive protease activity that cleaves cathelicidin into LL-37. Given these findings, a small prospective, open-label, interventional trial was undertaken to assess the effects of azelaic acid 15% gel on inflammatory lesions of papulopustular rosacea in a real-world setting. Use of azelaic acid was associated with a significant reduction in inflammatory lesions, which persisted beyond the active treatment phase. Overall, azelaic acid 15% gel is an appropriate initial topical therapy for the treatment of moderate facial rosacea.

Introduction

Rosacea is a common chronic cutaneous disorder that is estimated to affect close to 10% of Americans in the community setting.[1] It is characterized by central facial erythema, papules, pustules, telangiectasia, flushing, and swelling. The precise pathogenesis of rosacea remains unclear. Dysregulation of the innate immune system, overgrowth of commensal skin organisms, and aberrant neurovascular signaling have been implicated in the pathophysiology of rosacea.[2]

The facial skin of rosacea patients has been documented to exhibit increased baseline expression of cathelicidin antimicrobial peptide, LL-37 (the active form of cathelicidin), and kallikrein 5 (KLK5), the protease responsible for cleaving cathelicidin into LL-37.[3] In rosacea skin, KLK5 also cleaves cathelicidin into other abnormal peptide fragments. These forms of LL-37 are pro-inflammatory and stimulate angiogenesis, contributing to the clinical manifestations of rosacea. In addition, increased expression of toll-like receptor 2 (TLR2), a pattern recognition receptor, has been identified.[4] This may contribute to the enhanced inflammatory responses to exogenous trigger factors seen in rosacea.

Azelaic acid, a naturally occurring, saturated, straight-chained, 9-carbon atom dicarboxylic acid, is used topically for the treatment of papulopustular rosacea (PPR). Azelaic acid has been shown to have anti-inflammatory activity through reduction of the cathelicidin pathway that is upregulated in facial skin of patients with rosacea. In vitro studies performed using murine or human skin showed that azelaic acid directly inhibits KLK5 in cultured keratinocytes, KLK5 gene expression, TLR2 expression, and cathelicidin and LL-37 formation.[5,6] An in vivo study conducted in patients with PPR showed reduction in cathelicidin and KLK5 activity after treatment with azelaic acid 15% gel applied twice daily.[5] Azelaic acid also has known antimicrobial, antioxidant, and anti-keratinization effects.[7]

Clinical trials have shown that azelaic acid 15% gel is an effective and safe first-line topical monotherapy for patients with PPR.[8] Exposure to azelaic acid 15% gel has been associated with statistically significant reductions in inflammatory lesions of rosacea.[9] However, there is a lack of data in the literature on the use of azelaic acid 15% gel outside a clinical trial setting, in real-world clinical practice. The objective of this study was, therefore, to assess the effectiveness of azelaic acid 15% gel when used as monotherapy for the treatment of mild to moderate PPR in a real-world setting.

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