An Update on Migraine Prophylaxis

ROUGHLY 39 MILLION Americans are affected by migraine, of whom more than 28 million are adult women. Due to nausea, light and sound sensitivity, throbbing pain and visual disturbances, among other symptoms, migraine attacks are usually debilitating and can last from four hours to 72 hours.¹ As a result, many migraineurs miss out on social opportunities and have much less time to perform daily tasks due to the illness.

Healthcare workers who do not suffer from migraine often misunderstand the condition and the suffering induced by the attacks. A migraine is not merely a bad headache; it is a primary headache and neurological disorder, which places it in a league of its own (Table).² Causes are not fully understood, but the illness can be linked to heredity, sex, hormonal changes, diet, weather, sleep changes and sensory stimuli.^2,3 The pain is so awful that one sufferer describes migraine as a “red-hot waffle iron stuck to the side of my head.”⁴ It’s no wonder that migraine accounts for more than 800,000 emergency room visits in the U.S. annually.⁵

In addition to patients’ misery, employers endure migraine consequences. More than 90 percent of migraine sufferers, for example, are unable to work or function normally at work while experiencing one. According to a 2020 analysis, the annual economic burden of migraine in the U.S. is approximately $78 billion.¹

For decades, researchers have worked to understand migraine and to find new methods and medications to mitigate the excruciating pain and financial costs. Approximately 38 percent of patients with episodic migraine could benefit from preventive therapy, but surprisingly, less than 13 percent take prophylactic medications. Fortunately, this year looks brighter for migraineurs and employers with the efficacy of new drugs that promise to improve medication compliance and health.⁶

Yet, in today’s rapidly changing pharmaceutical scene, healthcare workers may struggle to stay current regarding migraine medications. Following is a brief rundown of what’s new and approved by the U.S. Food and Drug Administration (FDA).

Calcitonin Gene-Related Peptide (CGRP) Inhibitors as Migraine Prophylaxis

CGRP inhibitors are perhaps the most encouraging new prophylactics for migraine in decades. CGRP is a protein that, among other functionalities, carries pain signals along nerves. Its main role in migraine is to stimulate sensory nerves, causing inflammation, vasodilation throughout the meninges and inevitable pain. But it has been shown that by blocking CGRP or the receptor to which it links with an antibody, a very effective migraine treatment is possible.⁷

In fact, CGRP inhibitors demonstrate distinct advantages over more traditional migraine medications, including beta blockers, anti-seizure medications and antidepressants. What’s more, CGRP inhibitors don’t cause the same types of unpleasant side effects that can make other migraine medications hard or even impossible to take. Indeed, clinical trials have shown CGRP inhibitors have minimal side effects overall.⁸

There are two types of CGRP inhibitors: CGRP monoclonal antibody receptors and CGRP receptor antagonists, both of which work by interrupting the sequences that cause migraine pain, thereby relieving acute migraine in some cases and providing migraine prophylaxis in others.^8,9 Available in injectable and oral forms, most are approved for prevention alone, while others are approved for both prevention and treatment.⁵

While side effects of CGRP inhibitors are minimal for most people, the risk that a patient might react differently and more severely is still present. Common side effects include allergic reactions or hypersensitive skin; hives, rash, flushed skin; nausea, constipation or abdominal pain; fatigue; injection site reactions; weight loss; elevated liver enzyme blood tests; shortness of breath; soreness at injection site (for injectables); and muscle spasm.^6,9 Nevertheless, for many migraineurs, the minimal risk is very much worth the benefit of managing severe pain.

FDA-Approved Monoclonal Antibody Receptors

Ajovy (fremanezumab-vfrm) from Teva Pharmaceutical Industries, administered through subcutaneous injection, is a fully humanized monoclonal antibody that targets the CGRP ligand. It has been shown to reduce migraine days with a 225 mg monthly injection or a 675 mg injection given every three months. Research shows Ajovy reduced migraine by five days a month in patients with chronic migraine, and it reduced migraine by an average of three-and-a-half days a month when taken quarterly or monthly over a 12-week period. Overall, 32 percent of patients with chronic migraine and 46 percent with episodic migraine had their monthly migraine days reduced by at least 50 percent over a 12-week period. However, those who are pregnant, breastfeeding or planning to become pregnant should not take this medication.

Emgality (galcanezumab-gnlm) from Eli Lilly, administered through subcutaneous injection once monthly, is also a fully humanized monoclonal antibody that targets the CGRP ligand. It is effective in preventing migraine, as well as cluster headaches. Emgality can be given as a single 300 mg injection to relieve an acute cluster headache episode and repeated monthly if needed. However, to prevent migraine effectively, it is given as a 240 mg loading dose the first month followed by 120 mg monthly injections. Research shows the drug can reduce the number of monthly migraine days by 50 percent or more for some patients. However, individuals younger than 18 years and anyone considering pregnancy, becoming pregnant or breastfeeding should not take this medication.

Vyepti (eptinezumab-jjmr) from Lundbeck, administered through intravenous infusion once every three months, is also a fully humanized monoclonal antibody that targets the CGRP ligand. While 100 mg is the recommended dose, some migraineurs benefit from the available and approved 300 mg dose. Research shows that after a single dose of 100 mg, patients who took Vyepti had fewer migraine days, on average, over three months.

Aimovig (erenumab-aooe) from Amgen, administered through subcutaneous injection once monthly, is yet another fully humanized monoclonal antibody that works by binding to the CGRP receptor. Research shows a monthly 140 mg injection of Aimovig has been shown to increase the chance of decreasing migraine frequency to at least 50 percent for one year.¹⁰

FDA-Approved CGRP Receptor Antagonists

Qulipta (atogepant) from AbbVie, administered once daily in tablet form, is for migraine prevention only. Prescribed as a 10 mg, 30 mg or 60 mg daily dose, Qulipta has shown efficacy in reducing episodic migraine days at all doses. Clinical studies show it significantly reduced monthly migraine days across 12 weeks. However, individuals who have kidney or liver problems or who are pregnant, breastfeeding or planning to become pregnant should not take Qulipta.

Nurtec ODT (rimegepant) from Biohaven, administered in orally disintegrating tablet form every other day, has proven effective in increasing the chance of being pain-free within two hours of episodic migraine onset. Individuals take one 75 mg orally dissolved tablet at migraine onset and another if needed after at least two hours. Nurtec ODT can also be taken every other day for migraine prophylaxis, making it the only CGRP antagonist with FDA approval for both acute treatment and prevention of migraine. In a study of people who were prescribed either Nurtec ODT (669 people) or a placebo (682 people) to treat their migraine, more people taking Nurtec ODT experienced freedom from pain and other bothersome symptoms after two hours versus a placebo. And, those benefits were sustained through 48 hours for some people. In another study of people who were prescribed either Nurtec ODT (348 people) or a placebo (347 people) to prevent migraine, more people taking Nurtec ODT experienced reduced monthly migraine days. Again, those who have kidney or liver problems or who are pregnant, breastfeeding or planning to become pregnant should not take Nurtec ODT.¹⁰

Nurtec ODT is fast becoming the front-runner in migraine prophylaxis, possibly due to what Forbes calls “an all-out blitz advertising sales campaign,” but more likely because it is effective in both preventing migraine, as well as treating acute migraine pain, which is a novelty in migraine medication.⁵

A Boundless Contest

The rivalry among medications continues in the migraine prophylaxis contest. While it is a complex task for healthcare professionals to stay up to date about the new drugs that can best help individuals who suffer from this debilitating illness, it is also an exciting era for migraine prophylaxis developments and coming trends. The good news is future migraine treatment and prevention will likely greatly surpass the capabilities of current migraine prophylactics. But until then, healthcare providers have an excellent selection of medications that can help migraineurs end their suffering.