Clinical Pearls & Morning Reports
Chronic migraine is a leading cause of disability worldwide. Expert opinion has been that patients with chronic migraine should receive preventive treatment; however, these treatments may be underused, not adhered to, associated with side effects, or ineffective. Silberstein et al. conducted a 16-week, double-blind, randomized, placebo-controlled, phase 3 trial with a 12-week active-intervention phase to evaluate the efficacy, safety, and side-effect profile of two dose regimens of fremanezumab (monthly and quarterly) for the preventive treatment of chronic migraine. Read the Original Article here.
Q: What is the target of fremanezumab?
A: Fremanezumab is a humanized IgG2a monoclonal antibody that selectively and potently binds to calcitonin gene–related peptide (CGRP), a 37–amino acid neuropeptide involved in central and peripheral pathophysiological events of migraine. Fremanezumab targets both α and β isoforms of the CGRP ligand (not the receptor), has flexible dosing, and is administered by means of subcutaneous injection.
Q: Is fremanezumab beneficial for patients with chronic migraine?
A: The phase 3 trial of fremanezumab in chronic migraine conducted by Silberstein et al. showed a significant benefit of fremanezumab over placebo with respect to the average number of headache days per month (difference vs. placebo, approximately –2 days per month), the number of migraine days, and headache-related disability. Treatment effects were seen within 4 weeks after the initial dose.
A: In the trial by Silberstein et al., adverse events were reported for 64% of the patients receiving placebo, 70% of those receiving fremanezumab quarterly (P=0.06 vs. placebo), and 71% of those receiving fremanezumab monthly (P=0.03 vs. placebo). Events were mild to moderate in severity in 95 to 96% of the patients in the three groups. The most common adverse event was injection-site pain, which occurred in 30% of the patients in the fremanezumab-quarterly group, 26% of those in the fremanezumab-monthly group, and 28% of those in the placebo group. Injection-site induration and erythema were more frequent with fremanezumab than with placebo. Serious adverse events occurred in 2% of the patients given placebo, 1% of those given fremanezumab monthly, and less than 1% of those given fremanezumab quarterly.
A: Although the trial included patients with a long history of disease and those who had previously not had a response to or were currently taking preventive medications, it did not include patients with more refractory disease — those who had not had a response to at least two clusters of preventive medications or who had continuous headache. As in other clinical trials of migraine treatment, eligibility was still restricted to relatively healthy patients. Further studies will be needed to assess the safety and efficacy of fremanezumab in a population of patients with migraine and coexistent diseases.