In a head-to-head trial, 55.4% of patients on erenumab (Aimovig) cut their monthly migraine days by more than half. On topiramate (Topamax), the figure was 31.2%. That trial is one of the pillars of a position statement the American Headache Society updated on March 11, 2024.
The society’s wording is short and direct: “The CGRP targeting therapies are a first-line option for migraine prevention. Initiation of these therapies should not require trial and failure of non-specific migraine preventive medication approaches.”
What changed
CGRP inhibitors were the first drugs built specifically to prevent migraine. Everything used for prevention before 2018 began life as a treatment for something else: antidepressants, blood pressure drugs, antiseizure medications. The new drugs block calcitonin gene-related peptide, a small protein that is plentiful in the sensory nerves of the head and neck and helps carry pain signals.
There are two families. Monoclonal antibodies are used for prevention. Gepants, which are CGRP receptor antagonists, can serve as abortive or preventive medicines. Rimegepant (Nurtec) is given for acute or preventive treatment of episodic migraine, and atogepant (Qulipta) for prevention.
The 2021 consensus statement set a higher bar. Patients generally had to show they could not tolerate two or more standard preventives, or had not responded to an 8-week trial at an effective dose. Those standard options included beta-blockers such as metoprolol and propranolol, tricyclics such as amitriptyline, and venlafaxine or duloxetine. For chronic migraine, two quarterly onabotulinumtoxinA (Botox) injections could stand in for two oral drugs.
The 2024 update adds candesartan, the CGRP antibodies erenumab, fremanezumab, galcanezumab and eptinezumab, and the gepants atogepant and rimegepant to the first-line list. For chronic migraine, the gepant listed is atogepant.
The evidence
The older and newer preventives show similar efficacy. The CGRP antibodies, though, often come with better tolerability. In the erenumab and topiramate trial, 10.6% of the erenumab group stopped because of adverse events, against 38.9% on topiramate.
Staying on treatment is its own problem. Commercial insurance claims showed adherence to 14 oral standard-of-care drugs at 26-29% after six months and 17-20% after 12 months in people with chronic migraine. Other claims data pointed to better adherence for galcanezumab (Emgality) than for the oral options.
Against Botox in chronic migraine, anti-CGRP antibodies cut headache days by 11.9 at 12 months, compared with 7.6 for onabotulinumtoxinA. Reductions in MIDAS scores and in monthly acute medication use were also larger at 6 and 12 months.
The cost problem
Price is the catch. Generic propranolol (Inderal) runs about $1,400 a year for prevention. Twelve monthly doses of galcanezumab can cost up to $10,000. Because CGRP inhibitors are brand-name drugs, an insurer may place them on tier 3 with a copay of $300-600 a month, and prior authorization is still required for tier 2 and tier 3 drugs.
The society expects first-line status to lower those barriers. It urged insurers and providers to weigh more than the sticker price, citing the risk that migraine becomes chronic when good treatment is delayed. “Access to care should be modifiable based on medical need and individual circumstances,” the statement said.
Practical points for patients
If one CGRP inhibitor gives no relief after an adequate trial, trying another is reasonable. The drugs belong to one class but are not identical. Women of reproductive age should be counseled on contraception, since the drugs have not been studied in pregnant women. The antibodies have a long half-life, and patients are advised to avoid pregnancy for 6 months after the last dose. Gepants should be stopped 5-7 days before conception.
Patients who respond well may move from chronic to episodic migraine, use far fewer abortive drugs, or clear medication overuse headache. The society’s own caveat is that no medication works for everyone. Anyone considering a change in migraine treatment should talk it over with their doctor.
