What is the role of calcitonin gene-related peptide (CGRP) inhibitors in migraine prevention?

Updated: Oct 21, 2019
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Helmi L Lutsep, MD  more...
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Inhibiting the calcitonin gene-related peptide (CGRP) pathway is a new method to prevent migraines. CGRP is a potent vasodilator and is a key neuropeptide that is central to migraine pathophysiology. CGRP concentrations decrease following administration of triptans when treating a migraine attack. Three monoclonal antibodies that bind to the CGRP receptor were approved in the United States in 2018 (ie, erenumab, fremanezumab, galcanezumab).

The first CGRP inhibitor approved by the FDA for migraine prophylaxis was erenumab (Aimovig) in May 2018. Approval was based on findings from the LIBERTY, ARISE, and STRIVE clinical trials. [119, 120, 121]

The LIBERTY trial studied difficult-to-treat patients (n=246) with episodic migraine who had failed 2 to 4 previous treatment. Patients treated with erenumab 140 mg had about a 3-fold higher odds of having their migraine days cut by half or more compared with placebo. [119]

In the ARISE trial, 577 adults with episodic migraine were randomized to placebo or 70 mg erenumab (570 were included in efficacy analysis). Patients receiving erenumab experienced -2.9 days change in monthly migraine days, compared with -1.8 days for placebo (p < 0.001). A ≥50% reduction in monthly migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of (p = 0.010). Migraine-specific medication treatment days were reduced by -1.2 (erenumab) and -0.6 (placebo) days, a treatment difference of -0.6 (p = 0.002). [120]

The STRIVE clinical trial compared erenumab doses of 70-mg (n=317) or 140-mg (n=319) to placebo (n=319). The mean number of migraine days per month at baseline was 8.3 in the overall population; by months 4 through 6, the number of days was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the placebo group (P< 0.001 for each dose vs. placebo). [121]

Two additional CGRP inhibitors, fremanezumab (Ajovy) and galcanezumab (Emgality), were approved in September 2018.

Approval of fremanezumab was based on the HALO study. Fremanezumab was administered monthly or quarterly and compared with matching placebo. The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group (P< 0.001 for both comparisons with placebo). [122]

Galcanezumab’s approval was based on the EVOLVE clinical trials. Mean monthly migraine headache days were reduced by 4.3-4.7 and 4.2-4.6 days by galcanezumab 120 and 240 mg, respectively, and 2.3-2.8 days by placebo (both P < 0.001). [123, 124]

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