CGRP-targeted therapies herald a new era in migraine management

Calcitonin gene–related peptide (CGRP)–targeted therapies are likely to become a mainstay of migraine headache treatment in the coming decades as they have demonstrated efficacy for acute and preventive treatment, according to Dr Yi-Jing Zhao of Mount Elizabeth Hospital, Singapore, who spoke at AIM 2025.  

“CGRP-targeting therapies [both monoclonal antibodies and gepants] have become first-line options for migraine prevention in the US and Europe very shortly after their debut, revolutionizing migraine patient care,” said Zhao. “This is because they have demonstrated equal or greater efficacy compared with previous first-line therapies and have a good safety profile.” [Headache 2024;64:333-341; J Headache Pain 2022;23:67]

Acute Tx: Real-world efficacy in Chinese patients

“The effectiveness and tolerability of rimegepant [an anti-CGRP] have been demonstrated in the first real-world study on acute migraine therapy in Chinese patients,” reported Zhao. Rimegepant was found to be effective in treating migraine in the full cohort (n=99) as well as the prior-nonresponder (n=40) and rimegepant + eptinezumab (n=28) subgroups, with a significant decreasing trend in the proportion of patients experiencing moderate-to-severe pain postdose (p<0.05) and a marked increase in the proportion of patients who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24 and 48 hours postdose compared with predose. The onset of action was as early as 30 minutes, with benefits sustained through 48 hours. [J Headache Pain 2024;25:160]

Reduced headache frequency with long-term acute Tx

“Patients with pre-existing primary headache often develop high-frequency episodic migraine or chronic migraine due to overuse of headache medications,” she continued. “Overuse of triptans has been found to lead to medication overuse headache [MOH] earlier than other medications for acute treatment of headaches, such as analgesics.”

A post hoc analysis (n=1,044) of an open-label safety study showed that long-term use of rimegepant 75 mg as acute treatment on an as-needed basis reduced the mean number of monthly migraine days (MMD) over a 1-year period, without an increase in monthly tablets taken. [J Headache Pain 2022;23:10]

Another US retrospective cohort study of 19,818 patients found that significantly more patients in the rimegepant cohort persisted with treatment compared with those in the triptan cohort (75.8 vs 53.5 percent; p<0.001), regardless of specific triptan taken or chronic migraine status. “This indicates that, over time, rimegepant has some modifying effect in decreasing headache frequency without predisposing patients to MOH,” Zhao remarked.  [Jenkins A, et al, Pain Week 2024, poster abstract P-072]

Effective in preventive Tx

Clinical efficacy in preventive treatment was demonstrated in Study 305, where rimegepant 75 mg taken every other day resulted in significant reduction in mean MMD during observational weeks 9–12 (-4.3 vs -3.5 days with placebo; p=0.0099). In the long-term (12-month) open-label extension of the study, reduction in MMD averaged 6.2 months over 16 months. “This translates into giving the patient 1 week of their life back for every month they are living with headache,” noted Zhao.   [Lancet 2021;397:51-60; Lipton RB, et al, Medscape LIVE! Conference, Sept 20–22, 2022]

Patient education on preventive measures

“Migraine is easily treatable,” said Zhao. “For patients to benefit from these therapies, physicians should actively educate patients on the phases of migraine so that they can recognize an eminent attack and take preventive measures or medication during the premonitory phase,” she urged.