When I first covered the anti-CGRP medications, it was 2019, just 1 year after they had come out. Since then, we have much gained more exposure to these medications, though none are approved by the FDA for those under age 18 yet. We get asked all the time about these medications, and while they do represent an great advance in treating and preventing migraine, they are not ‘miracle drugs”. There are clinical trials going on now looking at safety and efficacy of these medications for teens, but it is a fairly long process.
What are these medications and what do they do?
CGRP stands for calcitonin gene-related peptide, a protein. CGRP does a number of jobs in the body, including pain transmission through the brain along the trigeminal nerve into the brain stem. Research has revealed increased levels of CGRP in both blood and saliva during a migraine attack. People with chronic migraine (more than 15 migraine days/month) had chronically elevated levels of CGRP. Researchers hypothesized that blocking CGRP and/or its receptor might play a role in migraine therapy. During migraine, CGRP can cause pain, nausea/vomiting, dizziness, photophobia, phonophobia and osmophobia.
There have been 3 monthly injectable medications developed with the purpose of blocking the release of CGRP proteins and/or its receptor. These medications work by using monoclonal antibodies, which target the neurotransmitter’s communication with the brain to block the CGRP release. With this process, the anti-CGRP medications block inflammation in the trigeminal nerve cells, prevent blood vessel dilation which causes pain, and inhibits pain signals.
These monoclonal antibodies are large molecules, reportedly too large to cross the blood brain barrier, and are not metabolized by the liver or excreted by the kidneys, decreasing the adverse renal or hepatic effects. They do not interact with other medications.
Aimovig (erenumab), the first released in May 2018) targets the CGRP receptor, and is given in monthly self-administered injections. Side effects reported are injection site irritation and constipation. It is available in both 70mg and 140mg doses,
Both Ajovy (fremanezumab) and Emgality (galcanezumab), released in September 2018, target the CGRP protein itself, and are also monthly self-administered injections. Side effects are injection site irritation, but not as much constipation, as well as fatigue, muscle spasms and cramps, and depression. Emgality dosing is 2 doses (240mg) in the first month and then 120mg/month (though insurance coverage often makes the double dose in the first month difficult to get). Ajovy is 225mg/month and can also be given every 3 months (675mg, but need to give 3 injectors- I have no personal experience with this dosing). All are approved for prevention of both episodic and chronic migraine.There can be hypersensitivity reactions to all three of the medications.
When you compare the medications, Aimovig reduces migraine days by 2.5 days/month and Emgality and Ajovy are comparable and reduce migraine days by 2-3 days/month. Some patients have achieved a reduction of 50% fewer headache days. If there is a partial response over the first 2 months, improvement in frequency may continue. However, if there is no response in the first 3 months, then the medication is not likely to be effective. If there is no response to one of these medications, then another could be tried, as it might be effective.
There is no real predictor for which one of the medications will work best for the individual patient. The decision is made on basically whichever medication the health insurance company has in its formulary. They generally will deny it if not on formulary, and insist on a trial of the formulary medication before approving any of the others. You need to show failure or significant side effects. This is a bit problematic for our patients with chronic constipation, in that it would be your clinical judgement not to use Aimovig The patient has to try Aimovig and show the lack of effect or worse constipation before another medication can be approved.
The age barrier is significant with these medications. Oftentimes, you can make a great case for trying the medication but if the patient is under age 18, it is automatically denied, and then denied again on appeal. We rarely go further than a 1st appeal as the result is usually not positive.Frankly it takes a lot of effort and time, without much hope for success.
Each of the pharmaceutical companies offer a discount or coupon plan for these medications, which reduces the cost significantly. This is not available for those under age 18. I recently priced it for someone who wanted to buy it without insurance approval, and it was going to be over $2000 for 3 injectors. That is more than most families can pay for something that might not magically eliminate migraines.
In a post in January 2022, I discussed the gepants, another new category of similar medications (oral), for use as rescue medications, to block CGRP. Nurtec (rimegepant) is also now being promoted as a preventive medications, given orally every other day. We have had mixed results with this protocol as far as effectiveness. There is also Qulipta (atogepant) which has been newly developed specifically as an oral migraine preventive. We have had no experience with Qulipta yet. There are clinical trials ongoing for the pediatric patient.
For those under age 18 years, there are significant barriers to access, including cost, lack of insurance approval, and no access to the discount plan..
Families often have unrealistic expectations of the medication, when in fact, even a positive effect can be quite modest in reducing migraine frequency.
The injections are painful! Use ice first before injecting to reduce the pain.
Sometimes the injectors fail, squirting the meds all over the place. Don’t throw it away! Contact the company as they will replace it.
Depending on the insurance, the pharmacy may only dispense 1 per month, despite the Rx ordering to dispense 3 month supply. This can be a problem.
The injectors needs to be refrigerated. Families will need to plan accordingly for potential travel. They may need a refrigerator in a dorm room, etc.
We have several clinical trials in our area. When a family REALLY wants the medication, we can refer them there. However, the trials often involve using a placebo, which for some families is unacceptable.
So are they worth it? For some of my over 18 patients, these medications have been very helpful. For some with really problematic chronic headache, a combination of an injectable med and Botox is needed to keep them functioning. For some, they have made no difference. It is good to have more options, though of course frustrating not to be able to access these options easily.