1. In this randomized controlled trial, Fremanezumab slightly decreased the amount of headache free days in those with episodic migraines compared to placebo.
2. Fremanezumab was associated with greater mild injection site reactions but not more serious adverse events.
Evidence Rating: 1 (Excellent)
Study Rundown: Fremanezumab, an anti-Calcitonin Gene-Related Peptide (anti-CGRP), has shown efficacy in reducing migraine symptoms in those with chronic migraine, representing the first approved drug designed specifically for migraine prophylaxis. However, most migraine sufferers have episodic migraines, defined as less than 15 days per month with migraine symptoms, and it is unclear if fremanezumab would benefit these patients. In this randomized controlled trial, monthly or quarterly fremanezumab was associated with a slight decrease in migraine-free days per month over a 3-month period compared placebo. Both treatments paradigms also resulted in a significant increase in 50% reduction of days with migraine, decrease in number of days using acute migraine medications, and a decrease in migraine symptom scores. While fremanezumab was associated with a greater amount of adverse events, mainly drive by an increase in injection-site reactions, it was not associated with serious adverse events or injection-site hemorrhage.
While this study supports expanding the indication for fremanezumab to patients with episodic migraines, further investigations are warranted. First, it is unclear if fremanezumab has increased benefit over other more established prophylactic drugs or if prolonged fremanezumab therapy will result in similar benefits to the sub-acute use in this trial. Further, the small effect size in terms of reduction in number of days with migraine dampens enthusiasm for this medication, though without head-to-head comparison against other prophylactics, this is hard to assess. Finally, this trial excluded patients who had failed multiple other prophylactic medications, and it is unclear if fremanezumab may be more efficacious for these patients.
Relevant Reading: Fremanezumab for the Preventive Treatment of Chronic Migraine
In-Depth [randomized controlled trial]: In this trial taking place in over 123 sites in 9 different countries, 791 patients (90% of recruited) with episodic migraine, defined as migraine for less than 15 days per month for at least one year, were randomized 1:1:1 to receive a monthly dose of fremanezumab, a one-time, high dose of fremanezumab as a quarterly dose, or placebo and were tracked over 12 months. Patients who had received botox injections, failed 2 or more prophylactic medications, or had TMS for migraines were excluded.
In terms of the primary endpoint, days with migraine, fremanezumab showed a significant decrease in both the monthly (mean difference -1.5 days; CI95 -2.01 to -0.93) and quarterly doses (-1.3; CI95 -1.79 to –0.72) compared to placebo. Both treatments paradigms also resulted in a significant increase in 50% reduction of days with migraine (monthly dose compared to placebo 19.8%; CI95 12.0% to 27.6%; quarterly 16.5%; CI95 8.9% to 24.1%), decrease in number of days using acute migraine medications (monthly dose compared to placebo -1.4 days; CI95 -1.84 to -0.89; quarterly -1.4 days; CI95 -1.76 to -0.82 days), and a decrease in migraine symptom scores on the MIDAS scale (monthly dose compared to placebo -7.0 points; CI95 -10.51 to -3.53; quarterly -5.4; CI95 -8.90 to -1.93). While fremanezumab was associated with a greater amount of adverse events (48% with monthly dosage, 47% with quarterly, 37% with placebo) mainly drive by an increase in injection-site reactions, it was not associated with serious adverse events or injection-site hemorrhage.
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