Eve Bender June 20, 2024
A position statement released by the American Headache Society (AHS) earlier this year recommended adding calcitonin gene-related peptide (CGRP)–targeting medications to the list of first-line therapies for migraine prevention.
The guidance replaces recommendations published in 2021 that advised clinicians consider CGRP therapy only after patients fail at least two classes of oral migraine prevention medications for ≥ 8 weeks.
“Elevating CGRP-targeting therapies to the first line should reduce barriers for patients to receive these effective treatments and bring hope to countless people who experience this invisible, yet debilitating disease,” Andrew Charles, MD, AHS president and the statement’s lead author, said in a press release.
Statement authors said the guidance is designed to reduce patient suffering and dispense with an unnecessary administrative burden for physicians. But will the new AHS position statement shape the way neurologists manage migraine? And if so, how?
Why Change Course Now?
In the 3 years following the AHS 2021 position statement, there’s been an “explosion” of evidence demonstrating the efficacy, safety, and tolerability of the CGRP inhibitors, Charles told Medscape Medical News. Consequently, the society conducted a series of town halls and meetings between 2022 and 2023 and appointed a task force to evaluate the strength of the evidence supporting migraine prevention treatments.
A literature review uncovered a number of placebo-controlled clinical trials and prospective and retrospective studies conducted at headache centers across the world, all showing that CGRP-targeting therapies offered statistically significant improvement in the prevention of episodic and chronic migraine.
Evidence from the PROMISE-2 trial showed that a 100- or 300-mg dose of eptinezumab at baseline reduced monthly migraine days by at least 75% during a 12-week trial compared with placebo.
The HER-MES trial, comparing erenumab and the anti-seizure medication topiramate, showed that patients taking erenumab reported at least a 50% reduction in migraine days vs a 31% reduction with topiramate.
In results from the 75-site PRODROME trial, treatment with 100 mg of ubrogepant during the prodrome period prevented the development of moderate/severe headache at both 24 and 48 hours post-dose.
Charles noted that these and other findings confirmed neurologists’ real-world experience with CGRP preventive therapies in terms of safety, efficacy, and tolerability.
Potential CGRP-associated side effects can include severe constipation, hypertension — primarily associated with erenumab — and worsening of Reynaud’s symptoms. However, CGRP inhibitors do not typically have to be discontinued.
A Clinical Practice Game Changer?
Prior to the development of CGRP-targeted therapies, migraine prevention relied on medications designed to treat other conditions including epilepsy, depression, or high blood pressure.
“The important distinction with these new therapies is that they were developed specifically for migraine, whereas with prevention medications that are nonspecific, there is more potential for adverse effects and the tolerability isn’t as good,” Charles said.
He also noted that nonspecific treatments tend to increase the stigma around disease. “Now that we’re actually able to treat migraine with a monoclonal antibody targeting a specific molecule, we have proof that migraine is a chemically and neurologically mediated disease.”
In theory, the AHS position statement means patients will no longer have to fail two other preventive medications — topiramate or a beta-blocker, for instance — before they can receive a CGRP inhibitor.
Studies suggest the change could have a real and positive impact on patient outcomes. One recent study showed that individuals with moderate to high frequency episodic migraine who failed two or more trials of preventive migraine medications had significantly worse health-related quality of life, higher depression and anxiety scores, and significantly more lost workdays than those who failed 0-1 trials of preventive medications.
The requirement of prior treatment failures also creates significant administrative challenges for neurologists, noted Charles. This process causes frustration for patients who are unable to take the medication their physician deems best without trying something else first, he noted.
“Frankly, some patients give up when they are forced to take medications that don’t work and cause them to feel lousy. They lose faith in the capacity of the medical system to help them,” he said.
Will Insurers Play Along?
Unfortunately, despite the new AHS guidance, some say that at least for now, patient frustration will likely continue.
“In my experience, it remains difficult to give a CGRP-targeted treatment to someone who has not tried and failed less expensive, oral generic medications. Many health plans still require failure of two oral medications before a CGRP-targeted treatment can be reimbursed,” Richard Lipton, MD, director of the Headache Center, Montefiore Medical Center, in Bronx, New York, told Medscape Medical News.
Lipton said he favors CGRP-targeted therapies over oral generics for several reasons, including more rapid onset of action and fewer side effects.
“While I agree that CGRP-targeted treatments should be first-line therapy for migraine prevention, prescribing is often dictated by rules for reimbursement,” Lipton added.
Historically, insurance companies have not covered CGRP inhibitors because of their high price tag. The price of once-monthly doses of erenumab fremanezumab without insurance run about $740 and $640, respectively.
“The elephant in the room is the high costs of these drugs,” Elizabeth Loder, MD, professor of neurology at Harvard Medical School, Boston, told Medscape Medical News. “[The consensus statement] seems to be a missed opportunity to point a more direct finger at the pharmaceutical industry as the main driver of access problems.”
While some of the pharmaceutical companies that manufacture CGRP inhibitors provide coupons to patients to use the drugs free of charge, Loder noted that these coupons only go to patients with commercial insurance. “These coupons are not for Medicare or Medicaid users, which is an inequity,” she said.
Drug companies offer financial assistance programs to people with public insurance, but “when you are disabled from migraines, it’s extremely arduous to complete all the paperwork necessary to qualify,” Loder added.
Charles noted that while the cost of the CGRP inhibitors is high, the cost of not taking them may be even higher due to expenditures for failed acute treatments, lost workdays/income, and damage to interpersonal relationships.
What’s Next?
In addition to the AHS, the American Academy of Neurology also plans to update its guidelines on migraine prevention to include CGRP inhibitors. However, an AAN spokesperson told Medscape Medical News that at this point, there is no timeline for the initiative.
Britain and Canada released guidelines that endorse the use of CGRP inhibitors, in 2021 and 2023, respectively.
A few of Charles’ colleagues have told him they are using the new AHS position statement to try to obtain insurance coverage for CGRP-targeting therapies for their patients. Others are using the new guidance to keep their patients on the medications.
“I have had some success using the position statement for formulary switching,” Jessica Ailani, MD, director of the Headache Center, Georgetown University, Washington, DC, told Medscape Medical News. “By doing so, I’m letting [the insurance companies know] that they shouldn’t remove my patients from their medications.”
“While we are arguing with the insurance companies, we risk having our patients bumped off their medications for some time,” she added.
In the meantime, Charles said he is keeping his focus on the future.
“These are extremely exciting times for the field of headache medicine,” he said. “We’ve got remarkable new treatments, and there are more on the way based on a much better understanding of migraine as a complex disorder of the nervous system.”
Charles has served as a compensated consultant for Amgen, Eli Lilly, eNeura, and Lundbeck. Loder had no disclosures. The AHS is a nonprofit organization that receives support from industry for educational programming, research, and advocacy. This includes support from multiple companies that are involved in the development, distribution, and marketing of therapies that are addressed in this statement, including (but not limited to) AbbVie, Amgen, Eli Lilly, Lundbeck, Pfizer, and Teva. These companies had no direct or indirect involvement in the development and writing of this consensus statement.
Leave a Reply