Efficacy of Extended-Release 45 mg Oral Minocycline and Extended-Release 45 mg Oral Minocycline Plus 15% Azelaic Acid in the Treatment of Acne Rosacea

Rosacea is one of the most commonly occurring dermatoses treated by dermatologists and affects approximately 16 million people in the United States¹ and 45 million people worldwide. Rosacea is an inflammatory dermatologic condition, classically presenting with flushing and/or blushing along with erythema, edema, telangiectasia, papules, pustules, and nodules of the face.² Although the underlying cause of this disorder is currently unknown, genetic and environmental factors are thought to contribute to its pathogenesis.³ There is evidence that aberrant cathelicidin production plays an important role in the cutaneous findings.⁴ The pathophysiology of rosacea is multifactorial, and triggering factors include stress, menopause, alcohol consumption, environmental exposures such as temperature extremes and sun exposure, certain foods such as spices, wind, and temperature extremes. The cutaneous findings are usually in the central face and composed of persistent erythema, telangiectasia, papules, and or pustules. The associated symptoms include pruritus, burning, and flushing.^5,6 There are 4 main subtypes of rosacea: erythematotelangiectatic, papulopustular, phymatous, and ocular.⁷

It is well established that rosacea is a chronic disease that may require long-term therapy such as topical and oral antibiotics, but this may lead to the development of antibiotic-resistant organisms.⁸ Inflammation plays a central role in the pathogenesis of rosacea and is usually treated with anti-inflammatory agents; flushing episodes are treated with vasoconstrictor agents, and telangiectasias with laser and light therapy.⁹

It has been well documented that rosacea is an inflammatory response to local factors and not an infectious disease.^3,5 It is important to utilize an agent that does not affect antimicrobial resistance while also impacting the disease. There are a variety of topical medications approved for the treatment of rosacea, but currently there is only one oral medication approved by the US Food and Drug Administration for the treatment of papulopustular rosacea, a subantimicrobial dose of doxycycline. Its effect has been demonstrated beyond its antimicrobial effects and may be more related to its anti-inflammatory capabilities, including but not limited to protease inhibtion.¹⁰ There are other oral agents utilized for the treatment of rosacea, including minocyline, tetracycline, sulfa-based antibiotics, and macrolides. Extended-release (ER) minocycline was formulated to avoid many of the side effects noted with high-dose minocycline. ER minocycline is produced in a variety of doses for use in acne, and dosing is based on weight. At the time of this study, the lowest available dose of ER minocycline, 45 mg, was delivered as a once-daily oral tablet.^11,12 The reasoning behind this study was to demonstrate the efficacy of the lowest possible dose utilizing the anti-inflammatory effects of minocycline in the treatment of patients with papulopustular rosacea, while avoiding the impact and side effects of high-dose minocycline (100-200 g/day). Azelaic acid has been utilized in the treatment of rosacea and was used topically once daily in the comparison group.^13,14 The objective of this study was to evaluate the safety, efficacy, and tolerability of ER 45 mg oral minocycline as monotherapy or combined with azelaic acid 15% in the treatment of rosacea.