LAS VEGAS – When patients with rosacea consult Julie C. Harper, MD, about persistent facial erythema, she often recommends brimonidine 0.33% gel or oxymetazoline 1% cream.
These remedies ‘work quickly’ and ‘quickly improve redness’ Harpersaid a dermatologist practicing in Birmingham, Alabama, at Society of Dermatology Physician Associates (SDPA) 22nd Annual Fall Dermatology Conference. Plus, she said, “You’ll know in 30 minutes or an hour whether it’s going to work or not.”
Brimonidine 0.33% gelan alpha-2 adrenergic receptor agonist, was approved by the US Food and Drug Administration (FDA) in 2014 for persistent facial erythema of rosacea. It does not treat telangiectasia and is not approved for flushing (transient erythema). Patients are advised to apply the gel daily in the morning. In phase 3 crucial tests of patients with moderate to severe erythema of rosacea, excluding those with more than two papules, a composite (investigator and patient reported) improvement of 2 degrees was observed as early as 30 minutes after application on day 1 and erythema was reduced for 9-12 hours.
Oxymetazoline 1% creaman alpha-1a adrenergic receptor agonist, was approved by the FDA in 2017 for persistent facial erythema of rosacea. It neither treats telangiectasia nor is it approved for flushing. Phase 3 studies patients with moderate to severe persistent erythema of rosacea excluded those with more than three inflammatory papules or pustules. As early as 1 hour after application on day 1, a composite (investigator and subject reported) improvement of 2 degrees was observed, and erythema decreased over 9-12 hours.
Differences in receptor selectivity
According to Harper, there are more reports of exacerbation of erythema with brimonidine 0.33% gel than with oxymetazoline 1% cream, perhaps because of the different receptor selectivity between the two products. She explained that alpha-1 receptors are located only postsynaptically in the vascular smooth muscle, while alpha-2 receptors are located presynaptically, which can inhibit norepinephrine and lead to vasodilation. Alpha-2 receptors are also located postsynaptically in vascular smooth muscle and in the endothelial wall, which can mediate nitric oxide release and cause vasodilation.
No head-to-head studies exist comparing brimonidine 0.33% gel with oxymetazoline 1% cream. But at one 52-week study of oxymetazoline 1% cream for persistent facial erythema associated with rosacea published in 2018, at week 52, 36.7% and 43.4% of patients achieved a composite improvement of 2 degrees or more from baseline in both Clinician Erythema Assessment as Subject Self-Assessment 3 and 6 hours respectively after a dose. Also, less than 1% of patients experienced a rebound effect after discontinuation of treatment.
“What we learned from this study is that patients may do better if they consistently use oxymetazoline 1% cream,” Harper said. “Does this mean that everyone I give this to uses it every day? Probably not, but I think we can change vascular tone by using it consistently every day.”
Oral beta blockers Another option
Alpha agonists can also help control flushing associated with rosacea, Harper continued, but oral beta blockers may be the better choice. In a 2020 judgement Based on nine studies, researchers evaluated the use of carvedilol, propranolol, nadolol, and beta blockers in general for rosacea-associated facial erythema and flushing. Articles studying carvedilol and propranolol showed a large reduction in erythema and flushing during treatment, with rapid onset of symptom control, while bradycardia and hypotension were the most commonly reported adverse events. “All of these agents have been studied in rosacea, but none of them have been approved by the FDA for rosacea,” Harper noted.
In one separate studyFive patients with rosacea who had severe frequent flushing or persistent erythema and burning sensations were treated with carvedilol, a non-selective beta-blocker. Previous treatments have included cetirizine and doxycycline, or isotretinoin combined with topical application of metronidazole gel or ivermectin without sufficient improvement of the erythema. Carvedilol was added to the above treatments and titrated to 12.5 mg twice daily and continued for at least 6 months.
The 5-point scale of the Clinician Erythema Assessment before therapy was 3.4 and decreased to 0.4 during therapy, while the patient’s self-assessment before therapy was 3.8 and decreased to 0.8 during therapy.
Another study evaluated the use of propranolol and/or doxycycline in 78 patients with rosacea. The propranolol and combination treatment groups showed faster improvement at weeks 4 and 8, but there was no statistically significant difference between them at week 12. Rosacea clinical scores also decreased in all groups, but there were no significant differences between them. The reduction in Rosacea clinical score assessment was 51%, 52.2% and 57.3% in the propranolol, doxycycline and combination groups, respectively.
Harper revealed ties to Almirall, Cutera, Galderma, Journey, Ortho Dermatologics and Sun Pharmaceutical Industries.
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