CGRP monoclonal antibodies : summary and effectiveness
Dr Elizabeth Leroux, MD, FRCPC
Disclaimer: this information is based on published data but may not be applicable to your specific medical situation. This information does not replace a medical opinion provided in person after a full evaluation and examination. Discuss ALL medical decisions with your health care provider. As this is a new class of medications, knowledge is changing quickly. Stay up to date with the help of your pharmacist and physician.
What is CGRP and how is it related to migraine?
CGRP (calcitonin gene-related peptide) is a substance that is naturally present in our bodies. It plays many roles, including stimulating sensory nerves, which causes pain, and dilating blood vessels. Research has shown that CGRP plays a role in migraine. Blocking CGRP, or the receptor it links to with an antibody could treat migraine. (See more HERE for our summary PDF LINKIN 915).
How many CGRP monoclonal antibodies (also known as MABs) are there? Are they different?
There are currently 4 MABs approved by Health Canada.
- Aimovig (erenumab)
- Ajovy (fremanezumab)
- Emgality (galcanezumab)
- Vyepti (eptinezumab)
CGRP monoclonal antibodies: a comparative table
|Type of antibody||Human||Humanized||Humanized||Humanized|
|Dose||70 or 140 mg||225 mg / month OR 225 x 3 doses every 3 months||120 mg / month (load first dose 120 mg x 2)||100 mg IV every 3 months|
|How to take it||Auto-injector||Auto-injector or Pre-filled Syringe||Auto-injector||Intra-veinous infusion|
|What is the target?||CGRP receptor||CGRP||CGRP||CGRP|
|Name of Patient Support Program||Aimovig GO||Ajovy Teva Support Solutions||Lilly Plus||Vyepti Today|
Who pays for these medications?
There are two main payers: public drug plans (government) and private insurance plans (through an employer).
Private insurers make their own decisions. Some private payers have decided to cover CGRP antibodies, usually with clinical criteria (headache frequency, previous medication failure).
Public insurers (linked to provincial Health Ministries) make decisions based on recommendations by an agency called CADTH.
All the medications listed above are available in Canada. Many private insurance companies have included these medications on their drug plans although the criteria from one insurance company to another may vary.
We are hopeful these medications will soon be covered by the provincial drug programs across Canada in the coming months. We will provide regular updates on our website and through social media channels. Until then, there is no public reimbursement/access in any province.
Patients do have the option to pay out of pocket with no financial support from the government or insurance companies*.
Share your voice about the importance of having access to medications and improving care for people living with migraine. Take a few minutes of your time and send a letter to your local elected official and Minister of Health through our seamless new advocacy platform. The process is seamless and simple!! Learn how here [ https://migrainecanada.org/advocacy/ ]
Patient Support Programs
Manufacturers commonly offer Patient Support Programs (PSPs) to support patients and healthcare professionals.
Enrollment is initiated by your physician and these programs usually include:
- Financial support, often to bridge the patient’s while reimbursement is secured through the insurance company.
- Support may also be given to provide financial support to patients who have a co-pay.
- Financial support to patients paying out of pocket (up to 20% co-pay)
- Note: All requests are reviewed on an individual basis by the patient support program.
General criteria for PSP financial assistance and private plan coverage (may vary from one company to the other):
- 8 days or more of migraine per month
- Two or more previous trials of migraine preventives with failure or intolerance
- Some insurance companies ask for a trial of Botox before trying a CGRP antibody.
Out of Pocket (Patient Pays)
Once a product is approved by Health Canada, patients with a prescription can pay for their medication(s) out of pocket. The CGRP’s are more expensive than the older medications (most are generic) and we encourage you to shop around by phoning a few pharmacies in your city/town. Prices may be different from one compared to another.
It is also important to call the manufacturer’s Patient Support Program to see if you may be eligible for some financial support (could be up to 20%) and will be assessed on case-by-case basis for financial assistance.
Does it make a difference if we target the receptor or CGRP itself?
We do not know that yet. This is a hot topic for researchers and experts but so far both the antibodies against CGRP and its receptor appear effective and safe according to clinical trials on thousands of patients.
What are my chances of responding positively to a CGRP antibody?
See our other post on this topic for Aimovig (LINKIN 915 PDF).
A response rate is the proportion of people who will improve after taking a treatment.
Example of 50% response: start with 12 days per month, down to 6
Example of 75% response: start with 20 days per month, down to 5
Overall here are a few ballpark approximative figures on response rates from the studies:
If 10 patients try a CGRP MAB, the following will experience:
- 50% response (episodic): 5-6/10
- 50% response (chronic): 4/10
- 75% response (episodic): 3/10
- 75% response (chronic): 2/10
- 100% response (episodic): 1/10
Episodic migraine: 1-14 days per month
Which CGRP antibody is the most effective?
CGRP antibodies have not been compared head-to-head to one another. They all have shown effectiveness in the prevention of episodic and chronic migraine in separate studies. There is a lot of variability in migraine in general. NO ONE SIZE FITS ALL! For example, the response to triptans varies from one person to the other. Likely some people will respond to one antibody, some to another, some to all and some to none.
Can I predict which CGRP antibody will work for me?
The only way to predict a response is to see to assess migraine frequency and intensity after starting any new medication. So, the short answer is NO. At the present time it cannot be predicted who will respond to a MAB or any medication for that matter.
If one does not work, should I try another?
Real world experience suggests that yes, people who don’t respond to one medication may still improve with a different one. If you have tried a MAB against the receptor (Aimovig is the only one), it may make sense to try a MAB against CGRP itself (Emgality, Ajovy or Viyepti). Still, even within the «ligand MAB» category, some patients might respond to one and not the other.
How long should I try a CGRP antibody before seeing a response?
Some people can respond quickly, as early as the first week. Others may take 4-5 months to see a response. In theory, people who have very severe migraines may need more time to improve. A standard trial would be 3 months, and a longer trial of 6 months may be justified in some people. It is important to again remember, everyone is difference and you should not compare response rate to others. It’s important to track your symptoms and discuss your personal situation with your healthcare professional.
Can I still improve if I have failed other treatments or if I have medication overuse?
Yes to both questions. Studies have shown that people who have failed other preventives (up to 11 in a Mayo Clinic study!) can still improve with CGRP antibodies. The same observation has been made for medication overuse. Interestingly, medication overuse and previous failures mostly decrease the placebo response (See this post). Please note that people taking opioids (morphine and other) were not included in any studies to date. Opioids should not be used to treat migraine. (See this post)
Other associations are also providing information on CGRP Antibodies:
- CGRP-Blocking Antibodies: Q&A With Dr. David Dodick
- What to Know About the New Anti CGRP Migraine Treatment Options
Updated: November 2022
An excellent summary article has been written by Dr Stewart Tepper:
Tepper SJ. History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment. Headache. 2018;58 Suppl 3:238-75.
A full reference list for CGRP antibody trials and clinical evidence can be found here (PDF CGRP references).
THE MIGRAINE TREE
- ACUTE TREATMENTS
- DEVICES AND NEUROMULATIOIN
- PREVENTIVE TREATMENTS
- PROCEDURES AND INJECTIONS
- SELF-CARE AND LIFESTYLE
- SOCIAL LIFE