CGRP Inhibitors Receive Reassuring Real-World Safety Report

Bruce Jancin

April 30, 2020

The first three calcitonin gene-related peptide (CGRP) inhibitors approved for prevention of migraine displayed a reassuring safety profile in real-world clinical practice during the first 6 months following their marketing launch, Stephen D. Silberstein, MD, reported online as part of the 2020 American Academy of Neurology Science Highlights.

He presented a retrospective analysis of spontaneous postmarketing reports to the Food and Drug Administration Adverse Events Reporting System (FAERS) for Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), and Emgality (galcanezumab-gnlm).

The top-10 lists of adverse events for all three monoclonal antibodies targeting CGRP were skewed heavily towards injection-site reactions, such as injection-site pain, itching, swelling, and erythema. The rates were relatively low. For example, injection-site pain was reported at a rate of 2.94 cases per 1,000 patients exposed to erenumab, 0.8/1,000 for fremanezumab, and 4.9/1,000 for galcanezumab, according to Dr. Silberstein, professor of neurology and director of the headache center at Sidney Kimmel Medical College, Philadelphia.

Migraine, headache, and drug ineffectiveness were in the top 10 for all three medications, as is typical in FAERS reports, since no drug is effective in everyone. These events were reported at rates of 1-5/1,000 exposed patients. Constipation was reported in association with the use of erenumab at a rate of 4.9 cases/1,000 patients, but did not reach the top-10 lists for the other two CGRP antagonists.

Notably, cardiovascular events were not among the top-10 adverse events reported for any of the novel preventive agents.

"These results will be practice changing, since some physicians have been holding back from prescribing these drugs pending the results of this sort of longer-term safety data," Dr. Silberstein predicted in an interview.

Asked to comment on the FAERS study, neurologist Holly Yancy, DO, said that she found the findings unsurprising because the adverse effects were essentially as expected based upon the earlier favorable clinical trials experience.

"These medications are living up to the expectations for good tolerability that were in place when they were initially approved by the FDA just under 2 years ago," said Dr. Yancy, a headache specialist at the Banner–University Medicine Neuroscience Institute in Phoenix.

"Injection-site reactions were anticipated. Clinically, I've found that if the medications reduce migraine days and severity, patients find the risk of temporary pain, redness, or itching at the injection site is an easy trade off," she added.

CGRP is a vasoactive peptide. There has been a theoretic concern that its pharmacologic inhibition for prevention of migraine could lead to an increased risk of adverse cardiovascular events, especially in individuals with coronary disease or a history of stroke. The absence of any such signal during the first 6 months of widespread clinical use of the CGRP inhibitors is highly encouraging, although this is an issue that warrants longer-term study, Dr. Yancy continued.

These drugs, which were expressly designed for migraine prevention, are a considerable advance over what was previously available in her view. They're equally or more effective and considerably better tolerated than the preventive medications physicians had long been using off label, including antidepressants, antiepileptics, and cardiac drugs.

Dr. Silberstein reported financial relationships with close to two dozen pharmaceutical companies. Dr. Yancy reported serving on speakers' bureaus for Amgen and Novartis.

SOURCE: Silverstein SD et al. AAN 2020, Abstract S58.008.

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