Facebook Live Recap with Dr. Stewart Tepper
In groundbreaking news for the migraine community, the FDA recently approved the first anti CGRP migraine treatments specifically created to prevent migraine. Designed to target CGRP, the protein known for causing migraine, these treatments are the biggest news in migraine treatment and prevention in decades. With one treatment option released on the market and three more expected in the next year and a half, migraine patients are asking if these treatments apply to them. The American Migraine Foundation sat down with Dr. Stewart Tepper, a professor of Neurology at the Geisel School of Medicine at Dartmouth and Director of the Dartmouth Headache Center at the Dartmouth-Hitchcock Medical Center, to answer the most pressing questions surrounding the monoclonal antibodies designed to target CGRP and the CGRP receptor.
What is CGRP?
CGRP stands for calcitonin gene-related peptide, and it is a protein that is released around the brain. When CGRP is released, it causes intense inflammation in the coverings of the brain (the meninges), and for most migraine patients, causes the pain of a migraine attack. In fact, if you give CGRP by an intravenous method to a person with migraine, within four hours, most of them will get a migraine. That’s the basis of all the new treatments.
How do the new drugs work and what is their relationship to CGRP?
Once it was determined that CGRP caused migraine, it became clear that if we could do something to stop CGRP, we could probably stop migraine. Four companies decided to create antibodies against CGRP and against the receptor to which CGRP binds. These large molecules are called monoclonal antibodies, and they do not cross into the brain. They are not eliminated by the liver. In fact, they are such big molecules that they have to be injected to get into the system. The drug approved last week, which is called erenumab, the brand name of which is Aimovig, is a monoclonal antibody against the CGRP receptor. The additional three are monoclonal antibodies against the CGRP protein.
What kind of side effects come with these treatments?
These drugs are extremely well tolerated. In fact, for most people, they don’t seem to have significant side effects other than some pain at the injection site.
How fast can one expect to see results?
With these new drugs, the monoclonal antibodies, most patients who are going to respond will see significant clinical benefit within a month. They are fast. For typical preventive medications, we usually work up to the correct dose and then we wait three months to see whether they’re effective.
How are these drugs administered?
The first three of the treatments are going to be by patient self-injection with a subcutaneous auto-injector at home. Two of them will always be monthly, and one of them will be either monthly or quarterly self-injection. The fourth one is going to be available by an intravenous infusion, which will be given every quarter, but patients would have to come into the doctor’s office to receive the fourth one, which we would expect at the end of next year or in 2020.
Who will benefit from these treatments?
The monoclonal antibodies have all been studied in episodic migraine and in chronic migraine and work in both, and they’re approved by the FDA for both, which is significant. These treatments are effective for migraine with aura or migraine without aura, for medication overuse and for no medication overuse. They have been proven to work in patients who have had a lack of success in two, three, and four previous preventive medications.
How much relief can patients expect to receive?
For patients with episodic migraine, that is less than 15 headache days per month, the new drugs dropped the number of migraine days per month by two to four days, generally around four days. If you multiply four days per month of no migraine times 12 months, then you have 48 days of no migraine per year, that otherwise would have been migraine days. That’s roughly a month and a half of no migraine per year compared to no treatment.
For the chronic migraine patients, those who have headache 15 or more headache days per month, these drugs dropped the number of migraine days by six to eight days per month. Of course, people with chronic migraine have more headache days per month to begin with, but six to eight days per month multiplied by 12 means that people could be expected to have at least two and a half months of no migraine, even three months of no migraine per year that they previously had migraine. That’s a pretty dramatic drop in the number of days of no migraine in a year and per month. That’s why we’re very, very excited.
Are there any reasons, another question, for pre-existing health condition or another medicine that would prevent somebody from receiving the treatments?
Erenumab, the drug that was approved, has been studied in patients with angina and heart disease. In that study, there was no impact on the angina in patients with pretty frequent angina. Erenumab has also been studied in people with risk factors for coronary disease and vascular disease without problems noted. There don’t seem to be any drug interactions that we know of with these monoclonal antibodies and other treatments. People would still be able to use their acute treatments when a migraine breaks through because for most people, these are not going to completely eliminate migraines. They’re going to help with frequency, severity, and duration.
Should people living with migraine approach this treatment option with caution, or is it a viable option for most?
I think that the insurance companies are going to limit the access to these drugs to people who have had a lack of success with two or three of the conventional preventive medications. Having said that, the one that was approved, erenumab was studied in people who had already had two to four preventive medication failures, and I mean complete failures. These were people that had taken antidepressants, anti-epilepsy drugs, anti-blood pressure drugs that were supposed to be effective for migraine prevention, and they had not worked at all. Then, they were given the monoclonal antibody, and it still seemed to work. The other monoclonal antibodies are also being studied people who have had a lack of success with their previous preventive treatments, and they also very good in terms of likelihood of success, even though people have had a lack of success with previous treatments.
Still, I don’t think we would give everybody with migraine this treatment option, because we’re likely to be limited by insurance and by cost. The more disabled people, the people that have tried the hardest and done the most and have still had a lack of success in reducing their migraines, are the candidates for whom these medicines should be made accessible.
Are the treatments expected to work for most migraine cases or for only specific types of migraine or symptoms?
These monoclonal antibodies were tested for migraine with aura, migraine without aura, episodic migraine, chronic migraine, medication overuse headache, and they worked equally well in every single one of those groups. If you are somebody who’s very disabled by migraine and has had a lack of success with prevention and if you currently have commercial insurance, a monoclonal antibody would be a very reasonable option.
If these treatments have been said only to alleviate a few headaches a month. Would it be worth it for me to try?
It is a gross under-estimate to think that these are only going to alleviate a few days per month. I think they’re going to reduce not just the frequency of migraine days per month but the intensity and the duration of the attacks, and they will likely help with the acute treatments as well because when people get their foot off the accelerator, the brake works better. They have also been shown to reduce the number of acute migraine treatments people need to take per month.
Are these treatments safe for women who are pregnant?
I certainly don’t want my patients who go on these to get pregnant. I am going to ask my patients to have very good birth control in place before we initiate the treatment. We don’t know about pregnancy safety, but monoclonal antibody effects last for months, and I don’t want one of my patients to be the one to try to find out whether there is a problem.
Is the treatment available only in the United States?
The United States is the first country to get the first anti-CGRP receptor monoclonal antibody, and we are the only country that has erenumab available.
Why is this so groundbreaking for migraine patients?
We’ve never had preventive medication designed for migraine in our lifetime. We’ve never had preventive medicines that are very, very well tolerated. All of our current preventive medicines have side effects that often prevent people from using them. We’ve never had preventive medicines that kick in and give significant clinical benefit within a month. If you add all of that up, this really seems like a watershed moment.
I really feel like the ground is shaking under our feet. I feel like this is a time when prevention and the way we treat migraine is about to change for the better, and I’m extremely happy for people with migraine across the country at this time.
For more information on the new anti CGRP treatments, please contact your healthcare professional.