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Treatment options for migraine have expanded considerably over the past two years, with several new classes of targeted, migraine-specific drugs coming to the market.

The expansion of therapies for acute migraine and migraine prevention is welcome news for migraine sufferers, many of whom do not get adequate relief despite trying multiple treatments.

For neurologists and others who treat migraine patients, the new options may provide a clearer rationale for how to approach treatment because, until recently, most of the drugs used for migraine were developed for other conditions such as epilepsy. The newer medications are designed to target pathophysiologic pathways involved in the migraine process in the hope of achieving better pain relief with fewer side effects.

“For our patients with migraine, we often have to say, ‘I am going to give you this medicine that was originally created to help seizures (or blood pressure, or depression), and it is going to help your headache,’” said Rebecca E. Wells, MD, MPH, associate professor of neurology and founder and director of the Comprehensive Headache Program at Wake Forest Baptist Health.

With the new drugs, she now can tell patients how the drug is different and how it targets the pathophysiology of how migraine is working in their brain.

The CGRP Inhibitors

Among the newer class of preventive drugs generating excitement are calcitonin gene-related peptide (CRGP) inhibitors, monoclonal antibodies that block a pathway involved in the migraine process.

“There are over 30 million people (in the US) with migraine, and yet only about 40 percent of them get adequate treatment,” said Jessica Ailani, MD, FAAN, director of Medstar Georgetown Headache Center and professor of clinical neurology at Medstar Georgetown University Hospital.

She and other migraine experts say the newer migraine drugs aren't a panacea for all patients and don't render obsolete the older, less expensive migraine therapies that work well for many people. But they hope that a broader range of treatments will lead to more people being effectively treated and sticking with their medicines because of fewer side effects.

“We are definitely seeing more patients come back to the practice we haven't seen in a while,” said Dr. Ailani. “Some patients come in saying, ‘I hear there is something new.’”

Erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality) are humanized monoclonal antibodies that block CGRP by either binding to the CGRP receptor (erenumab) or binding to the CGRP ligand (fremanezumab and galcanezumab).

The injectables are administered every one to three months, depending on the drug. Erenumab carries a warning of possible hypersensitivity reactions, and the drug can also cause severe constipation. Galcanezumab is also approved for cluster headaches.

Epitenezumab (Vyepti), which works by binding to the CGRP ligand, is the first approved intravenous treatment for migraine prevention. It is administered via IV infusion at a clinic every three months. Because the drug was approved by the US Food and Drug Administration (FDA) in February just as the pandemic was taking off in the US, doctors say they have minimal experience in prescribing it.

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