New Understanding of Migraine Biology Paves Way for Innovative Therapy Options

Now that investigators have a better understanding of the biological mechanisms of migraine, new treatment and prevention options are making their way to patients and fueling an exciting time for the field, according to a presenter at the National Association of Managed Care Physicians Virtual Spring Managed Care Forum.

Andrew Charles, MD, professor of neurology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) and director of the UCLA Goldberg Migraine Program, kicked off his talk by outlining the burdens of migraine as a public health issue. It is the second leading cause of time spent disabled worldwide, according to the World Health Organization, and is often comorbid with other issues like depression, anxiety, and neck pain, placing migraine at the hub of the most disabling disorders on the planet.

Charles spoke of the traditional ideas about migraine that had to be dispelled to set the stage for new therapies. The vascular theory—that spasms and vasodilation of blood vessels cause migraine—has been around for decades, but recent research has shown that dilation is neither necessary nor sufficient to explain the condition, and investigators have begun to understand migraine as so much more than just about blood vessels. In addition to the debunking of the vascular theory, the multifaceted symptoms of migraine and the involvement of different brain structures throughout an attack have given rise to the idea of migraine as a “complex neurovascular event involving multiple brain regions and symptoms,” Charles said.

Diagnosis of migraine has also evolved in recent years, as more providers are moving away from using the complex International Classification of Headache Disorders criteria toward a simplified 3-question screener, ID Migraine, which asks patients simple questions about photophobia, impairment, and nausea. This screening has good specificity and sensitivity, as 93% of those who answer “yes” to at least 2 of the questions have migraine.

Once a diagnosis is in place, clinicians and patients work together to identify triggers, but Charles cautioned that some supposed triggers may actually be symptoms (eg, bright light may seem to be a trigger, but photophobia is an early symptom of a migraine attack). In terms of lifestyle changes, he emphasized that a focus on achieving consistency in one’s diet, sleep, caffeine intake, and exercise is more realistic and effective than radical changes.

The go-to acute therapy for migraines is the triptan class, but for patients whose migraines are interfering with their daily lives despite acute treatment, preventive therapies are available. Interestingly, there are no real biomarkers indicating which patients will respond to which therapy, so prescribers tend to choose based on patients’ other comorbidities. For instance, a patient who needs to lose weight may want to try the antiepileptic drug topiramate, whereas one with insomnia may see benefits from an antidepressant such as amitriptyline.

Recent advances have brought new migraine-specific therapies to the market. Lasmiditan is a selective 5HT1F agonist that can be used for acute treatment in place of a triptan, especially for those with cardiovascular disorder, in whom triptans are contraindicated.

Another major breakthrough was the realization of the role of calcitonin gene-related peptide (CGRP) in migraine. “There’s a very solid foundation of evidence supporting the use of therapies targeting CGRP,” Charles said, including that CGRP administration can trigger a migraine attack, showing that it is not just correlated but actually a causative event.

There are now 2 small-molecule CGRP receptor antagonists approved by the FDA for acute migraine treatment, ubrogepant and rimegepant, and these have the strengths of a longer half-life than most triptans and no vascular contraindications.

Additionally, there are now 4 large-molecule monoclonal antibodies (mAbs) in use: erenumab, galcanezumab, fremanezumab, and eptinezumab. They were approved by the FDA starting in May 2018. Unlike the small molecules, these agents have high target specificity, a longer half-life, and different methods of administration (subcutaneous or intravenous rather than oral).

Charles noted that the real-world experience with these drugs has shown that their impressive efficacy even exceeds that seen in clinical trials. “We’ve heard the words ‘my life has changed’ more over the last 3 years than over the last couple of decades within our practice,” Charles said.

Looking to the horizon, he noted that the “gepant” small-molecule CGRP drugs are currently in trials to test whether they are effective for migraine prevention. The major questions remaining in the field of migraine center around prioritizing treatments for migraine and predicting therapeutic response to the various options.

“These are very, very exciting times for those with migraine and those of us who take care of the millions of people in this country who suffer from this disabling disease,” he summarized.