Treatment of papules and pustules
For treating papules and pustules, the 2019 systemic review also found high-certainty evidence for using azelaic acid and topical ivermectin, and moderate-certainty evidence for using topical metronidazole and topical minocycline. “Topical ivermectin was demonstrated to be the most effective topical treatment for papulopustular rosacea and to provide the greatest psychological benefit to these patients,” Dr. Graber said.
In a double-blind, multicenter 15-week trial comparing azelaic acid 15% gel with metronidazole 0.75% gel in patients with papulopustular rosacea, both agents were found to be effective. But those treated with azelaic acid 15% gel had a greater reduction in lesion counts and erythema, and improvement in global assessments, compared with metronidazole 0.75% gel. However, the azelaic acid 15% gel was associated with more stinging compared with metronidazole 0.75% gel, although it was usually transient.
Another study, a double-blind, single-center, 15-week trial, compared the efficacy of azelaic acid 20% cream with metronidazole 0.75% cream. Both agents were found to be effective and had similar levels of reductions in papules and pustules. However, patients in the azelaic acid 20% cream arm had significantly higher physician ratings of global improvement, as well as overall higher patient satisfaction.
More recently, a phase 3 study of 962 patients found that ivermectin 1% cream once daily improved quality of life slightly more than metronidazole 0.75% cream twice daily. No difference in adverse events were noted between the two agents.
Other options for treating papules and pustules include topical minocycline 1.5% foam, which is FDA approved for rosacea, as well as second-line agents topical sodium sulfacetamide with sulfur cleanser (cream or lotion), and permethrin, Dr. Graber said.
As for treating papules and pustules with oral agents, the strongest evidence favors oral tetracyclines and isotretinoin, she noted.
Doxycycline, minocycline, tetracycline, and sarecycline can be used as monotherapy or coadministered with topical agents. “The addition of topical agents may also help to shorten the duration of antibiotic use, which is very important,” Dr. Graber said.
She noted that oral beta-blockers might be useful to treat persistent erythema and flushing because they antagonize the effects of sympathetic nerve stimulation and circulating catecholamines at b-adrenoceptors. Carvedilol and propranolol have been the most studied. The most common potential side effects are hypotension and bradycardia.
Dr. Graber disclosed that she is a consultant/adviser for Digital Diagnostics, Almirall, Hovione, Keratin Biosciences, La Roche Posay, Ortho Dermatologics, Sebacia, Sol-Gel, Verrica, and WebMD. She is also a research investigator for Hovione, Ortho Dermatologics, Sebacia, and she receives royalties from Wolters Kluwer Health.
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