CGRP Monoclonal Antibody May Reduce Flushing, Chronic Erythema in Rosacea
Calcitonin gene-related peptides are known to trigger vasodilation and inflammation.
Calcitonin gene-related peptide (CGRP)-receptor monoclonal antibody erenumab may be effective in reducing flushing and chronic erythema associated with rosacea, according to research results published in JAMA Dermatology.1 CGRP has been previously associated with pathogenesis of rosacea due to its triggering of vasodilation and inflammation.1,2
In an effort to evaluate effectiveness, tolerability, and safety of erenumab for this patient population, researchers in Denmark conducted a single-center, open-label, single-group, nonrandomized controlled trial (NCT04419259) between June 2020 and May 2021. Adults with rosacea with at least 15 days of moderate to severe erythema and/or moderate to extreme flushing were eligible to participate. All participants received subcutaneous erenumab 140 mg every 4 weeks for a total of 12 weeks, with a safety follow-up visit at week 20.
The primary study outcome was mean change in the number of monthly days with moderate to extreme flushing from baseline to weeks 9 through 12. Flushing severity was evaluated using item 2 of the Flushing Assessment Tool (FAST); erythema severity was evaluated through the Clinician Erythema Assessment, and overall rosacea severity was evaluated through the Investigator Global Assessment, the Rosacea Area and Severity Index, and the Rosacea Clinical Scorecard.
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Secondary study outcomes included mean change in FAST from baseline to weeks 1 to 4 and weeks 5 to 8; proportion of patients with at least a 50% reduction in the number of days with moderate, severe, or extreme flushing from weeks 9 to 12; mean change in scores from baseline to weeks 4, 8, and 20 on the Clinician Erythema Assessment, the Investigator Global Assessment, the Rosacea Area and Severity Index, the Rosacea Clinical Scorecard, and the Inflammatory Lesion Count; and mean change in Patient Self Assessment; and mean change in quality of life.
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Thirty participants were included in the study cohort (mean age, 38.8±13.1 years; 77% women); 3 participants discontinued the study, leaving 27 patients for final analyses. Before trial enrollment, 26 participants had discontinued at least 1 rosacea treatment due to a lack of effectiveness or tolerability; topical treatments included azelaic acid, brimonidine, ivermectin, and/or metronidazole, while oral treatments included beta blockers, doxycycline, isotretinoin, and/or tetracycline.
At baseline, mean number of days with moderate to extreme flushing per 4 weeks was 23.6±5.8 days. By weeks 9 through 12, the number of days with moderate to extreme flushing had decreased by a mean of -6.9 days, with 1 patient experiencing at least a 50% reduction from baseline to weeks 1 through 4. An additional 3 patients experienced at least a 50% reduction from weeks 5 to 9, and 7 patients experience the reduction from weeks 9 to 12. In patients with more than 10 days per month of severe to extreme flushing, investigators noted a decrease from 30.8 days per month at baseline to 3.8 days per month at weeks 9 through 12—a reduction of 81%.
In terms of secondary outcomes, mean number of days with moderate to severe erythema reduced by -8.1 days, from 15.2±9.1 days at baseline, with the majority of participants (56%) experiencing at least a 50% reduction by weeks 9 to 12. Mean Clinician Erythema Assessment score reduced by -0.67 points by week 8, from 2.93 at baseline; mean Investigator Global Assessment score reduced by -0.63 points, from 2.96±0.44 at baseline and Rosacea Area and Severity Index score reduced by -2.68 points from 10.37 at baseline, both by week 8. No significant changes were noted in Rosacea Clinical Scorecard scores and Inflammatory Lesion Count by week 8 or week 20.
Mean quality of life score was 6.22±4.99 at baseline, with a reduction of -2.08 and -2.73 points at week 8 and week 20, respectively.
In terms of safety, 83% of patients experienced at least 1 adverse event. Common adverse events included constipation, transient worsening of flushing, bloating, upper respiratory tract infection, transient worsening of headache or migraine, dry eye, dry skin, and/or transient fever.
Study limitations included the open-label design, the lack of placebo group, and the “relatively short” follow-up period.
“This nonrandomized controlled trial provides evidence to support the potential effectiveness of erenumab in managing chronic redness and flushing in individuals with rosacea, as demonstrated by the reduction in days with moderate to extreme flushing,” the researchers concluded. Larger randomized, controlled, double blind clinical trials are necessary to both confirm these results and investigate long-term effects of erenumab therapy.
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