Experts Say CGRP Drugs Are First-Line Therapies for Migraine Prevention

By Pat Anson, PNN Editor

Migraine medications that block calcitonin gene-related peptides (CGRPs) are “equal to or greater” than other migraine prevention drugs and should be considered first-line therapies, according to a new guideline from the American Headache Society (AHS).

It’s the first time the organization has endorsed CGRP inhibitors for migraine prevention, despite their high cost and limited availability due to insurance requirements. Many insurers have step-therapy policies that require patients to start with cheaper first-line treatments before trying other 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," Andrew Charles, MD, AHS president and lead author of the guideline recently published in the journal Headache. 

CGRP inhibitors block a protein that binds to nerve receptors in the brain and trigger migraine pain. Since 2018, the FDA has approved over half a dozen CGRP medications for migraine prevention and/or treatment, the biggest innovation in migraine therapy in decades.   

Older drugs that have long been used for migraine prevention were originally developed for other conditions. They include amitriptyline, a tricyclic antidepressant; simvastatin, which is used to control cholesterol; topiramate (Topamax), an antiseizure medication; and beta-blockers commonly used to control blood pressure.  

The AHS says there is growing “real world” experience that CGRP inhibitors work better than the older, repurposed medications.

“The evidence for the efficacy, tolerability, and safety of CGRP-targeting migraine preventive therapies is substantial, and vastly exceeds that for any other preventive treatment approach,” the AHS said. “The data indicates that the efficacy and tolerability of CGRP-targeting therapies are equal to or greater than those of previous first-line therapies and that serious adverse events associated with CGRP-targeting therapies are rare.”

The biggest problem with CGRP inhibitors is their cost, which can reach tens of thousands of dollars a year. Eight doses of Nurtec, a tablet taken daily, cost over $1,000; while the listed price for Emgality is $706 for a self-injectable syringe used monthly. Prices will vary, depending on insurance and whether a patient qualifies for discounts or patient assistance programs.

By comparison, amitriptyline and simvastatin are bargains. A bottle of 30 simvastatin tablets will cost about $14, while amitriptyline costs about $13 for a supply of 28 tablets. A recent study suggests that amitriptyline and simvastatin work just as well as CGRP inhibitors in reducing the need for medications to treat migraine pain, an indication that they are effective at prevention.

Despite the disparity in cost, the AHS maintains the overall benefits of CGRP inhibitors may justify the price. There are substantial hidden costs to migraine attacks, which can result in lost productivity, income, education, and personal relationships.   

“We recognize that the CGRP-targeting preventive therapies are significantly more expensive on a yearly basis than most of the previously established therapies, and some argue that this expense is a primary consideration in clinical decision-making,” the AHS said. “On the other hand, we argue that it is critically important to consider not only the direct cost of the treatment but also the substantial costs to the individual and society if effective treatment is delayed.”

Migraine affects about 39 million people in the United States and 1.1 billion worldwide. In addition to headache pain, migraine can cause nausea, blurriness, and sensitivity to light or sound. Women are three times more likely to suffer from migraines than men.  

Why Women Are More Likely to Suffer Migraines

By Pat Anson, PNN Editor

German scientists may have finally proven a link between hormones and migraines, and why women suffer migraines at triple the rate that men do. In studies on animals and humans, researchers found that calcitonin gene-related peptides (CGRPs) increase in females during menstruation.

CGRP is a protein that binds to nerve receptors and dilates blood vessels in the brain, causing migraine pain. Several medications are now on the market that inhibit CGRP, one of the biggest innovations in migraine treatment in decades.

“This elevated level of CGRP following hormonal fluctuations could help to explain why migraine attacks are more likely during menstruation and why migraine attacks gradually decline after menopause,” says Bianca Raffaelli, MD, of Charité – Universitätsmedizin Berlin in Germany. “These results need to be confirmed with larger studies, but we’re hopeful that they will help us better understand the migraine process.”

Raffaelli and her colleagues measured CGRP levels in the blood and tear fluid of 180 women during their menstrual cycles, and found that those who suffer from episodic migraines had significantly higher concentrations of CGRP during menstruation, when estrogen levels are low.

“This means that when estrogen levels drop immediately before the start of a menstrual period, migraine patients release more CGRP,” said Raffaelli, lead author of a study published in the journal Neurology. “This could explain why these patients suffer more migraine attacks just before and during their monthly period.”

In women who take oral contraceptives, there were hardly any fluctuations in their estrogen or CGRP levels. The same was true for postmenopausal women.

“Taking birth control pills and the end of menopause do in fact bring relief for some female migraine patients. But as our study also shows, there are women who suffer from migraine even without any hormonal fluctuations. We suspect that other processes in the body play a role in triggering attacks in those patients. After all, CGRP isn’t the only inflammatory peptide that can cause a migraine attack,” said Raffaelli.

The study also suggests that measuring CGRP levels in tear fluid is feasible and warrants further investigation, because accurately measuring CGRP in the blood is challenging due to its short half-life.

The research team now plans to study how other physical processes are influenced by the menstrual cycle, such as blood vessels and brain function. They also plan to take a closer look at CGRP levels in men of varying age groups.

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound.