Newer Anti-CGRP Migraine Prevention Drugs Should Be First-Line Treatment, Says American Headache Society
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People with migraine may now get relief sooner, under new guidelines that recommend patients start therapy with newer medicines that specifically target the headaches and other symptoms of this complex neurological disorder — instead of using older and less effective drugs first.
Those older drugs, designed for other conditions and repurposed for migraine attacks, have long been the first option offered to patients for prevention — including therapies like the antiseizure medicine topiramate (Topamax), the antidepressant amitriptyline, and blood pressure pills known as beta-blockers. Up until now, newer therapies targeting calcitonin gene-related peptide (CGRP), a protein directly involved in causing migraine, have been reserved as backup options after people tried and failed to find relief with older drugs.
“Moving CGRP-targeting therapies to the first line of treatment could have a transformational impact on the prevention of migraine attacks and their associated burdens,” says Andrew Charles, MD, the lead author of the statement, the president of the American Headache Society, and the director of the migraine program at the University of California in Los Angeles.
What Are Anti-CGRP Therapies?
CGRP is a protein in the brain and nervous system that plays a role in pain transmission and the way that tissues and blood vessels respond to pain. Blood levels of CGRP are elevated when a migraine attack strikes, and subside when these attacks are effectively treated.
Targeted CGRP therapies can prevent migraine attacks by blocking the ability of this protein to transmit pain signals in the nervous system, says Chia-Chun Chiang, MD, a headache specialist and an assistant professor of neurology at Mayo Clinic in Rochester, Minnesota.
“These treatments can keep the blood vessels in the brain from reacting in a way that leads to migraine attacks,” says Dr. Chiang, who wasn’t involved in the position statement.
According to Nada Hindiyeh, MD, the director of headache neurology at the Metrodora Institute in West Valley City, Utah, there are five CGRP targeted therapies that work for migraine prevention:
Some CGRP drugs can also be used to treat symptoms when people have an acute migraine attack, including the pills ubrogepant (Ubrelvy) and rimegepant as well as the nasal spray zavegepant (Zavzpret). This is known as abortive treatment, intended to reduce CGRP levels so that migraine symptoms ease.
“All patients will require an acute treatment for their migraine attacks, whether it’s a CGRP antagonist or other option,” Dr. Hindiyeh says. “And many patients will need a preventive as well.”
The goal with CGRP targeted therapies for prevention is to reduce the frequency and severity of acute migraine attacks, especially for chronic migraine, which is defined as 15 or more days with migraine symptoms per month. So it makes sense for people with migraine to try these drugs first, or to consider switching to CGRP therapies if they started with something else, says Huma Sheikh, MD, an assistant professor of neurology at the Icahn School of Medicine at Mount Sinai in New York City.
“For some patients who have chronic migraine, this class of medication is added on to other therapies in hopes that they will work in conjunction to have a better effect,” Dr. Sheikh says.
Why Earlier CGRP Treatment Helps With Migraine
Because older traditional migraine treatments were developed for different purposes, they can have side effects or cause problems for people with certain health conditions, which make them hard to tolerate or unsafe to use, says Lauren Natbony, MD, the medical director at Integrative Headache Medicine of New York. Starting with these can delay effective treatment, or lead some patients to give up trying to achieve relief, Dr. Natbony adds.
“On the other hand, CGRPs have demonstrated superior efficacy compared with many current treatments, and patients typically experience faster symptom relief,” Natbony says. “They are generally well-tolerated with few or no side effects.”
Up until now, patients have faced delays getting CGRP targeted therapies because insurance coverage often won’t kick in until after patients have tried older options that failed, Natbony says. “Moreover, the higher cost and the often-required prior authorization for CGRP therapies present additional barriers to access.”
The new treatment guidelines should help address these access challenges. “This shift in treatment strategy could significantly improve patient outcomes, especially for those who have not benefited from traditional therapies or who are unable to tolerate them,” Natbony says. “Essentially, we would be giving patients the best possible treatment for their condition first rather than waiting to try other treatments that might not work as well.”
Still, the new guidelines don’t mean older medications and therapies will be disregarded altogether. Many people have found relief from combination therapy, using the older migraine prevention drugs such as onabotulinumtoxinA (Botox for migraine) along with the new ones.
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