Kaitlyn was 10 years old when she had her first migraine.
At the time, she had no name for it. She only knew that the lights suddenly became too bright in the room in the church where her mother led a Girl Scout troop. Kaitlyn ran to the bathroom – also harshly lighted – and threw up. The experience was as mysterious as it was traumatic.
“I remember it clearly. I didn’t understand what it was. We wrote it off as something weird,” said Kaitlyn, who prefers not to use her last name.
It wasn’t long before Kaitlyn, now 29, and her parents couldn’t write it off. She suffered through more episodes like the first one, and they became more frequent. After about a year and a half, she was struggling through the attacks more often than not. A pediatrician finally diagnosed the problem as migraine – a neurologic disease frequently misidentified as severe headache. It affects nearly 40 million people in the United States alone; about 10 percent of those are chronic sufferers (at least 15 episodes a month).
Kaitlyn had identified her childhood foe but finding the weapons to battle it proved elusive. Nearly two decades later, migraine remains a defining feature of her life. She hasn’t worked in nearly a year and a half. Pain, fatigue, and cognitive difficulties are nearly constant, unwelcome companions. Because of migraine, Kaitlyn is frequently homebound, unable to get outside or hang out with friends.
“It limits a lot of what is possible,” she said.
In May, Kaitlyn, and millions of other people who suffer from episodic (between four and 14 episodes a month) and chronic migraine received a note of hope. The Food and Drug Administration approved Aimovig, the first medication developed specifically for migraine prevention. It’s a once-a-month treatment that patients self-administer through an autoinjector that looks like an EpiPen with the aim of preventing, rather than treating, migraine attacks.
“It’s a new option for patients,” said Marius Birlea, MD, a neurologist and medical director of the Headache Clinic at UCHealth University of Colorado Hospital on the Anschutz Medical Campus.
Aimovig targets the neuro pathway for calcitonin gene related peptide (CGRP), a protein specifically implicated in causing migraine. The pathway has been studied for over two decades, Birlea said. Early work used small molecules to successfully block the CGRP’s receptor. However, the effort was shelved because the molecules caused liver damage. Aimovig skirts this issue with a monoclonal antibody – one designed to bind specifically to the CGRP receptor – that doesn’t require clearance through the liver or kidneys, Birlea explained.
Aimovig “is not a panacea,” Birlea emphasized, and it will not supplant an array of treatments he prescribes for migraine. But the clinical trial results were promising: for chronic sufferers, more than two fewer days of migraine a month versus a placebo. In a separate study of migraine patients who had not gotten relief from other treatments, those who received Aimovig were about twice as likely to see a 50 percent reduction in their migraine days as those who received a placebo. The drug was also free of side effects frequently produced by other migraine medications, such as fatigue, concentration problems and weight gain.
The findings as a whole are significant, Birlea said. “The study showed that for patients who received Aimovig, migraines were less frequent and less disabling,” he noted. “And our goal with preventive treatment is to decrease the burden of migraine by at least 50 percent.”
Only a first step
Aimovig’s minimal side effects and the need to administer it just once a month should encourage patients to adhere to their treatment regimen, Birlea added. While there are no contraindications in the label, experts are looking for more data before determining if these medications will be offered to pregnant women, those who are breastfeeding or plan to, and people at high risk for cardiovascular disease and stroke, he said. As part of its approval, the FDA also “requested” that Amgen, the manufacturer of Aimovig, conduct “post-marketing surveillance” of patients for these potential issues and for liver toxicity.
“There are some unknowns about the potential side effects of Aimovig, although no concerning signals came out of studies involving about 2,500 subjects,” Birlea said.
As might be expected, the cost of the drug also generated discussion. Amgen listed it at $6,900 a year, or $575 a monthly dose. To begin, patients may receive their first two doses free, and Amgen announced a copay program that would allow some patients to pay as little as $5 a month for the medication. Birlea also pointed to a recent study that argues that erenumab, the antibody in Aimovig that blocks the CGRP receptor, will reduce the direct and indirect costs of migraine while increasing the number of “quality-adjusted life years,” a measure of the cost-effectiveness of medical treatment.
Birlea didn’t participate in the erenumab (Aimovig) trials, but he’ll be an active observer in evaluating its effectiveness going forward. One day after the FDA gave the go-ahead for writing Aimovig prescriptions in late May, Birlea said he’d already written three – one of them for Kaitlyn. He estimated that the drug could benefit as many as 2,000 patients the Headache Clinic treats for migraine.
“We see the most severe cases,” Birlea said.
Aimovig offers promise for specialists outside of neurology. For example, Rachael Rzasa Lynn, MD, medical director of the Pain Management Clinic at UCH, treats migraine sufferers with a variety of techniques, including Botox injections, nerve blocks and medications. She said she called Birlea after hearing news of the FDA approval to discuss adding Aimovig to her array of migraine treatment options.
“It’s not a magic bullet,” Rzasa Lynn said, “but it’s impressive how few major exclusions it has. It could be useful for a broad spectrum of patients.”
She emphasized that Botox is established as an effective, FDA-approved preventive treatment for chronic migraine, and she expects “the vast majority” of patients will continue with it. “Botox does a very good job of relieving the debilitating pain and vomiting that migraine causes while allowing people to stay fully functional. We’ll see if Aimovig can do the same.”
If it does, Aimovig could be an important alternative to patients who haven’t responded to Botox, Rzasa Lynn said. Others could find self-administering their treatment once a month with Aimovig preferable to Botox, which requires injections at 31 different sites in the face and neck every three months, she added.
Migraine shuts down the show
Kaitlyn’s experience with migraine illuminates the excitement news of the Aimovig approval generated. The chronic migraines she endured through middle school and her early high school years gradually abated and were nearly gone by the time she entered NYU as a theater major. Other than a couple of episodes exacerbated by what she later learned was an allergy to triptans, a widely prescribed group of migraine medications, she was mostly migraine-free and worked steadily for several years, shuttling between Washington, D.C. and California as a stage and production manager for theater groups.
In 2015, however, Kaitlyn began experiencing persistent pain she thought were sinus headaches. To get through long hours on both coasts, she took what she now acknowledges were excessive doses of over-the-counter medications. “I tried to push through the pain,” she said. “It was seven or eight months before I started taking it seriously.”
At that point she had no choice. While she was working in California that summer, Kaitlyn began passing out. Her hair fell out in chunks, and she battled a bout of hives. She encountered severe digestive problems. She chalked it up to stress and decided to find another job, but an otolaryngologist in the District who heard her history concluded that her migraines had returned and sent her to a neurologist. She spent three or four days in the hospital for rest and to cleanse her system of the over-the-counter medications that she now knows can cause migraines to rebound. She worked with neurologists in the District to find relief from the disease that so disrupted her life.
The ordeal, however, continues, and migraines are a nearly constant presence for her. “I have good days and bad days,” Kaitlyn said. Bad weather is a trigger, as is bright light, dehydration and fatigue. She describes the pain from her migraines as intense sinus pressure that starts deep in her ears and spreads.
She wants people to understand that a migraine is not simply a severe headache. “Migraines are a neurologic disorder; headaches are not,” she said. “For the most part, people who have headaches have the ability to push it to the side and continue to do their work. A migraine for me is a true breakdown of my body. It’s like the computer chips start to break down in my head.”
Search for relief
Kaitlyn began seeing Birlea for her migraines after moving to Colorado with her boyfriend last November. She credits Birlea for a number of treatments that have improved her symptoms. They include tweaking her medications; prescribing an SPG (sphenopalatine ganglion) block, which delivers pain-numbing lidocaine to nerves implicated in migraine via nasal injections; and ordering two procedures that use her own blood to patch a cerebrospinal fluid leak that may exacerbate her migraine symptoms.
The first of those procedures produced two weeks of pain-free mornings, Kaitlyn said, something she hadn’t experienced in more than two years. The second was less successful, but it still helped to keep her more functional during the day.
“I’d seen multiple neurologists and none of them considered a cerebrospinal fluid leak,” she said.
Birlea also keeps Kaitlyn’s prescribed mix of medications in the Epic electronic health record, allowing her to get relief from a severe attack quickly by visiting the Infusion Center at UCH. Without that option in the District, her migraine attacks forced her to the emergency department, where she often sat for hours under bright fluorescent lights before getting medications of “whatever they had on hand.”
“I can also talk to Dr. Birlea about changing my medications when something isn’t working as well as I’d like,” Kaitlyn said. “The back-and-forth is incredible. The last six months of treatment I’ve gotten more care and options than I’ve gotten the past three years.”
As for Aimovig, Kaitlyn was well aware of the trials and was elated when she heard of its approval. “I’ve had my eye on it, she said. “I’m pretty excited about it.” Her treatment goals are basic: more opportunities to get outside to camp and hike, travel, meet with friends and, most of all, work.
“I tied my identity to being able to work,” she said. “Not being able to work removes a lot of feelings of self-worth in my life.”
Birlea sees the Aimovig approval as an important first step in expanding the range of migraine treatments for both providers and patients. He anticipates more options coming online soon. Three other preventive treatments that block CGRP itself, rather than the receptor, have been developed, he noted.
“It’s extremely exciting,” he said. “We will be able to develop guidelines for how to choose these medications for patients and how to use them in combinations.”