New Migraine Prevention Guidance Highlights CGRP Drugs, Broad Eligibility

New guidance from the American Academy of Neurology (AAN) and the American Headache Society (AHS) aims to help clinicians identify which migraine prevention drugs may be most effective for certain patients.

The guidelines — the first update since 2012 — were published in Neurology and were based on evidence from a systematic review of migraine prevention drugs, said author Rebecca Burch, MD, of the University of Vermont Larner College of Medicine in Burlington.

“Since the previous guidelines were published in 2012, there has been a wealth of new treatment available for prevention of migraine, and specifically, the migraine-specific CGRP [calcitonin gene-related peptide]-targeted therapy category,” Burch noted in a press briefing.

CGRP is a potent vasodilator thought to play a significant role in migraine. In 2018, erenumab (Aimovig), an injectable treatment targeting CGRP receptors, was the first monoclonal antibody approved for migraine prevention; fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti) soon followed. Oral CGRP receptor antagonists rimegepant (Nurtec) and atogepant (Qulipta) were approved for migraine prevention in 2021.

Earlier drugs approved for migraine prevention include onabotulinumtoxinA (Botox), the antiseizure medications topiramate (Topamax) and valproate, and the beta-blocker propranolol. Other treatments are used off-label.

“The guideline says preventive treatments should be offered to people who experience 4 or more migraine days per month or 4 or more moderate-to-severe headache days per month, or if migraine is affecting their ability to work or complete daily tasks,” Burch said.

It includes recommendations for both episodic migraine and chronic migraine — headache that occurs 15 or more days a month which, on at least 8 days a month, has the features of migraine headache.

The systematic review included 217 studies published through June 4, 2024. For episodic migraine, galcanezumab and erenumab outperformed placebo in reducing headache frequency, with high-confidence evidence, the review showed. Atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate showed benefits with moderate-confidence evidence.

For chronic migraine, high-confidence evidence indicated patients had fewer headaches with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefits with atogepant, eptinezumab, erenumab, topiramate, and valproate.

In both types of migraine, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate, and onabotulinumtoxinA led to improvements in patient-reported quality-of-life outcomes. Studies comparing treatments were limited.

Unlike previous guidance, the update includes “specific recommendations according to different areas that patients may prioritize or care about more, including effectiveness, side-effect profile, long-term history of safe use, and cost,” Burch noted.

“The research shows many different types of medications may be effective for preventing migraine attacks and reducing symptoms,” she added. “If one type of medication is not working well, a different type may still be effective. It is important for clinicians and patients to know that there are many options.”

Burch pointed out that she and her co-authors also make “some recommendations about an approach to treatment in pregnancy.”

Neurologic conditions are the leading cause of disability worldwide, and migraine accounts for one of the highest levels of disability-adjusted life-years.

“Migraine is a chronic disease that typically fluctuates over the course of a person’s life,” Burch said. Besides headache, attacks are often associated with nausea and sensitivity to light or sound, and can impair functioning.

“We know from studies of the U.S. population that many more patients with migraine are eligible for preventive treatment,” she added. “One of the goals with this guideline was to be clear about who is eligible for prevention, and it really is more people than are receiving preventive treatment right now.”