In a recent multinational clinical trial, researchers evaluated the effectiveness of two fremanezumab regimens for chronic migraine prevention.
The transmission of pain signals during migraines is thought to be carried out in part by the release of calcitonin gene-related peptide (CGRP) from one nerve and reception by the next. Early trials have shown that fremanezumab, an antibody therapy which targets CGRP and prevents its reception, reduces the number of days in which chronic migraine sufferers experience migraines and headaches. To determine the utility of fremanezumab as a preventative treatment for chronic migraine, its safety and efficacy under different regimens must be tested.
Can Fremanezumab Prevent Migraines?
In a recent trial published in the New England Journal of Medicine, researchers investigated the safety and efficacy of fremanezumab for the prevention of a chronic migraine. Otherwise healthy patients from nine different countries aged 18-70 years experiencing migraines for the past 12 months were recruited for the study. Those who experienced persistent headaches for fewer than 15 days per month or migraine headaches for fewer than eight days per month, who had recently received other treatments for chronic migraines, or who had taken opioids or barbiturates at least four times in the last 28 days were excluded.
Patients were randomly assigned to receive one of three regimens. The Fremanezumab + Placebo group received 675 mg of fremanezumab at the start of the trial, followed by 1.5 mL placebo injections at weeks 4 and 8. The Fremanezumab group received 675 mg of fremanuzemab at the start of the trial and 225 mg/1.5 mL at weeks 4 and 8. The Placebo group received 4.5 mL of placebo at the start of the trial and 1.5 mL at weeks 4 and 8. Patients recorded information concerning the severity, duration, and frequency of headaches and migraine symptoms experienced throughout the study.
In total, 1,130 patients took part in the study: 376 were assigned to the Fremanezumab + Placebo group, 379 to the Fremanezumab group, and 375 to the Placebo group. The average number of headache days at the start of the trial was 13.2 in the Fremanezumab + Placebo group, 12.8 in the Fremanezumab group, and 13.3 in the Placebo group. The average number of headache days over the 12-week period was 8.5 in the Fremanezumab + Placebo group, 8.0 in the Fremanezumab group, and 10.4 in the Placebo group.
Fremanezumab Reduces the Frequency of Migraines
The average number of headache days over the 12-week period was reduced by 4.3 days in the Fremanezumab + Placebo group, 4.6 days in the Fremanezumab + Placebo group, and 2.5 days in the Placebo group. Per month, the average number of headache days was reduced by 50% or greater in 38%, 41%, and 18% of participants and there were average reductions of 4.9 days, 5.0 days, and 3.2 days. Headache-related disability decreased by 6.4 points, 6.8 points, and 4.5 points (on a 42-point scale) after week 8.
Mild to moderate adverse events occurred in 70% of Fremanezumab + Placebo patients, 71% of Fremanezumab patients, and 60% of placebo patients. The most common mild to moderate adverse events were pain, thickening and hardening of the skin, and redness at the site of injection. Liver dysfunction was observed in eight patients (0.8%), three of whom were in the Placebo group.
Fremanezumab May Be an Effective Therapy
These findings suggest that fremanezumab is an effective preventative therapy for a chronic migraine. The two regimens tested were similarly effective in reducing the average number of headache days and headache severity among patients. Though adverse events were common, the majority were mild to moderate in nature and may be attributable in part to the method of delivery, that is, injection under the skin.
As the study population was otherwise healthy, future research would benefit from exploring the efficacy of fremanezumab in patients with conditions which affect the risk of a migraine or a headache, such as obesity or certain infections. To determine the long-term safety and efficacy of fremanezumab, larger trials with longer study periods will still be necessary.
Written by Raishard Haynes, MBS
Reference: Silberstein, S.D. et al. (2017). Fremanezumab for the Preventive Treatment of Chronic Migraine. N Engl J Med 2017; 377:2113-22. DOI: 10.1056/NEJMoa1709038