How to Prescribe Monoclonal Antibodies for Migraine

Internist Vincent Martin, MD, said every primary care clinician should know about calcitonin gene-related peptide (CGRP) monoclonal antibodies for preventing migraines. These newer drugs are changing the lives of his patients.

“These should be primary care meds,” said Martin, director of the Headache and Facial Pain Center at the University of Cincinnati Gardner Neuroscience Institute in Cincinnati. Physicians “can dramatically improve the quality of their migraine patients just by learning how to use this group of medications.”

Many of his patients who formerly could not tolerate or had inadequate responses to conventional migraine medications are now doing very well with the CGRP agents.

Until recently, patients have had trouble accessing the newer drugs without going through step therapy with less expensive, older medications. But Andrew Charles, MD, director of the UCLA Goldberg Migraine Program, said he has recently heard from colleagues that insurers are easing access.

In March, the American Headache Society published a position statement calling for CGRP monoclonal antibodies to be used as first-line treatment for migraine prevention. Charles, a professor of neurology at UCLA’s David Geffen School of Medicine, co-authored the new guidelines.

“They are more expensive, yes, but because they work so well — really better than anything else out there — we should think about them as a first-line approach,” he said.

The US Food and Drug Administration (FDA) has approved four CGRP monoclonal antibodies: Erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti). Eptinezumab is given quarterly by intravenous, typically in an infusion setting. The others are monthly injections patients can self-administer at home. Fremanezumab also can be administered on a quarterly dosing schedule as three shots every 3 months.

Fremanezumab, galcanezumab, and eptinezumab target CGRP, a protein that increases in the bloodstream during a migraine and recedes after. Erenumab targets the receptor to which CGRP binds.

The Headache Society recommends use of CGRP monoclonal antibodies for patients who have episodic migraine, with or without an aura, for 4-14 migraine days per month based upon the International Classification of Headache Disorders, third edition, and for whom the migraine produces at least moderate disability. The group also recommends the drugs for patients who have chronic migraine, with or without aura, and who have 15 or more migraine days per month.

Nearly any adult who regularly experiences migraine could be a candidate, with few exceptions such as pregnant people, Charles said. All previous migraine prevention therapies like beta-blockers, antidepressants, and anti-seizure medications were developed for other indications and later adopted for migraine. The antibodies targeting CGRP, however, were developed specifically for migraine.

“The old, conventional preventive therapies took 1-3 months to work. In some instances, these medications can work in a week or less — their onset of action is much quicker,” Martin told Medscape Medical News.

The autoinjectors are similar to other devices used in patient-administered medications such as epinephrine or diabetes medications, Martin said. For instructions, a pharmacist can help, or clinicians can refer patients to online videos produced by manufacturers.

Side effects are minimal, such as injection site reactions, he said. Erenumab, the first to receive approval, in rare cases can cause constipation or elevated blood pressure, he said.

Not all insurers have adopted the Headache Society guidelines for the products, which can cost from $300 to $1000 per month using insurance coverage. Many plans require fail-first policies with two older preventive medications such as beta-blockers, tricyclic antidepressants, or topiramate, Martin said.

But about one third of people who should be on these preventive therapies for migraine are not taking them, said Jason Rosenberg, MD, a neurologist with Mercy Medical Center in Baltimore, who has specialty certification in headache medicine.

“A day with full-blown migraine is essentially a lost day,” he said. “You’re out of commission, you’re not a computer, you’re not on a phone, you’re not working, you’ve lost that day of your life. The first lesson is you’re got to identify the people that should be on a preventive.”

Rosenberg said he uses asthma as an analogy: If someone has an occasional asthma attack, they can use a rescue medicine. If a patient is wheezing all the time, they need to be on a maintenance drug.

“They’re both what we call chronic diseases with episodic manifestations. The disease is always there, but if the symptoms are bad or frequent, you want to treat them to suppress the symptoms rather than treat after the fact,” Rosenberg said.

Some patients may not know about preventive medications, and some primary care clinicians may not be aware to ask patients about migraines, Rosenberg said.

“They may hear, ‘Somebody has migraines; I’ll give them an as-needed drug’. But if [patients are] losing days of the month to their headaches, they really ought to be on a preventive medicine,” Rosenberg said. Individuals who do not respond to migraine treatment or who have neurologic symptoms such as auras should especially be considered for the preventive drugs.

Some primary care physicians seem more comfortable instead prescribing gepants for migraine prevention, Charles said. These small molecules, available as oral tablets, work similarly to the monoclonal antibodies but must be taken daily or every other day. Two are FDA-approved for migraine prevention: Rimegepant (Nurtec) and atogepant (Qulipta).

More drugs are on the horizon for the treatment of migraines.

One target is pituitary adenylate cyclase-activating polypeptide (PACAP). A phase 2 trial reported in The New England Journal of Medicine in September found a single 750 mg infusion of a monoclonal antibody directed against the PACAP ligand reduced the frequency of migraine by about 6 days over the subsequent 4 weeks.

“These are very, very exciting times for migraine,” Charles said. “There are now multiple other monoclonal antibodies with other targets on the horizon, so it really is a new era of treatment.”

Karen Blum is a freelance medical/science writer in the Baltimore area.