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CGRP monoclonal antibodies : summary and effectiveness

Dr Elizabeth Leroux, MD, FRCPC 

October 2019 

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 [1]. 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? 

Please note that Ajovy is NOT available in Canada yet. It is expected in 2020.  

CGRP monoclonal antibodies: a comparative table

Brand nameAimovigEmgalityAjovy
Chemical nameErenumabGalcanezumabFremanezumab
Type of antibodyHumanHumanizedHumanized
Dose70 or 140 mg120 mg(load first dose 120 mg x 2)225 mg / month OR225 x 3 doses every 3 months
How to take itAuto-injectorAuto-injectorSyringe
What is the target?CGRP receptorCGRPCGRP
What is the cost per dose? $ 535 CAD70 and 140 mg same price$ 623 CADComing 2020
Name of Patient Support ProgramAimovig GOLilly PlusComing 2020


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). If there is an interest in this topic for more data about all the drugs more information could be made available. 

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, how many will experience:

Episodic migraine: 1-14 days per month

Chronic migraine [2]: >15 days per month, 8 of which with migraine attacks (See this post [3])

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 [4] 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? 

Well…the only way to predict a response is to see if a person has a migraine after receiving IV CGRP, which is done in research in Denmark. But that’s for research only. 

So in  practice NO, at present time we cannot predict who will respond to a MAB. 

If one does not work, should I try another?

Real world experience suggests that yes, people who don’t respond to a MAB 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 or Ajovy).  

How long should I try a CGRP antibody before seeing a response? 

Some people respond very fast, 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. 

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 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 [5]). 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 [6])

Other associations are also providing information on CGRP Antibodies: 

REFERENCES

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 [9]). 

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