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10 Articles in this Series
An AAPM 2019 Preview
APRNs/PAs in Pain Medicine SIG Gets Underway
Cannabis Has Entered Pain Management and Is Here to Stay: What Clinicians Need to Consider
Managing Pain in Marginalized Populations, including Ethnic Minorities, LGBTQ, and the Obese
Neuromodulation: A Roundtable on Current Best Practice & Key Questions
Pro/Con: CGRP Antibodies and Treatment Choice for Chronic Migraine
Pro/Con: Conservative Care is the Best Route for Chronic Pelvic Pain
Pro/Con: CRPS - Use Everything but Stimulation
Pro/Con: Ketamine for Complex Regional Pain Syndrome, Neuropathic Pain, and More
Pro/Con: Radiofrequency Denervation is Effective (The MINT Studies)

Pro/Con: CGRP Antibodies and Treatment Choice for Chronic Migraine

A Pro-Con Debate* on the following statement, held at the 2019 annual meeting of the American Academy of Pain Medicine (AAPM):  "CGRP Antibodies May Be the Treatment of Choice for Chronic Migraine."

PRO, offered by Alan M. Rapoport, MD:

When we start a migraineur on a new preventive therapy, of any kind, there is an 83% chance that they will be off it at the end of the year and we know there are multiple possible adverse events causing this. We now have 3 new CGRP ligand or receptor blockers available and their long-term benefits are unknown as the first one released has only been on the market since May 2018. However, there have been very few serious adverse events in about 10,000 patients in all the clinical trials. We now have over 200,000 patients who have tried these therapies in the real world. All primary endpoint data for these new migraine preventive therapies have shown a reduction in mean monthly migraine days that is statistically better than placebo. While using such an endpoint is key for FDA approval, this data is not something I like to talk to my patients about. For instance, I cannot say to a patient: “This new treatment is fairly expensive and it may reduce your headache days 1.3 days more than if you take a placebo injection.”

However, if I focus on the secondary endpoints, I can compare them to those of current migraine preventives which tend to only provide mediocre efficacy with no specificity for migraine, not to mention lots of potential adverse events, poor adherence, and they often require long lead times to find the right dose to achieve benefit. Everyone today talks about the 50% responder rate—that is, at least 50% of headaches per month are gone in 50% of patients treated, such as reducing 10 headaches a month to 5 headaches a month. Some even had 75% response rates of 20% (20% of patients in a trial had 75% of their headaches gone each month). All of this is clinically relevant as these patients had multiple failures with previous trials of other preventives.

This new class has wide therapeutic targets—episodic migraine, chronic migraine and possibly cluster headache. It is also very effective in treating medication overuse headache (MOH), which is the biggest problem I see in my patients with chronic migraine. The time to onset of efficacy is less than 1 week, whereas the older drugs took 2-3 months to be effective. These treatments cause few side effects and improve patients' global impression of change. They reduce days of acute medication use as well as produce a big decrease in disability. They are well tolerated and there are no contraindications! Thus, if safety is confirmed and, so far, it looks ok, these preventive biologics could be considered first-line treatments in the future. This potential paradigm shift will depend on cost and access, which is improving as we speak. 

My takeaway: One must always be cautious about a new type of treatment. We should use it wisely. But rather than be overly concerned about theoretical side effects, we should offer these new monoclonal antibodies to CGRP or its receptor to our most difficult-to-treat migraineurs who have failed multiple other treatments and have lots of disability. Otherwise, it will be hard to treat them effectively.

CON, offered by Robert B. Cowan, MD, FAAN, FAHS:

I have nothing to argue on the points made by Dr. Rapoport—everything he said is true, but what is important to keep in mind are all of the things that he did not say. The lack of safety data for CGRP monoclonal antibodies (mAb), for example, was not presented. Patients in the clinical trials were very carefully selected.

Think back to the drug Vioxx, which was withdrawn from the market after 100 million prescriptions were written. So far, about 200,000 CGRP prescriptions have been written. Long-term effects are not known although there is emerging 5-year data, including the potential impact on wound healing and the cardiovascular system, where CGRP participates in the inflammatory process and is present in nerve fibers that innervate blood vessels in the heart, among other functions. How might CGRP mAb in the body affect a patient who has a traumatic head injury or a myocardial infarction with circulating mAbs? Look at the GI and CNS systems—CGRP mAbs are not selective and affect receptors and ligands throughout the body and some CNS structures are not protected by the blood-brain barrier. We do not know if this is a problem and neither do the manufacturers. Read more about what may be at stake regarding unknowns about the CGRPs.

What about hemiplegic migraine patients—could an attack become a completed stroke because CGRP is not there to facilitate recovery? We need CGRP in our systems. The FDA FAERS reports to date are complaints, they are not validated, but there were 8,000 as of December 31, 2018 for Aimovig (erenumab-aooe), in particular, which has been out the longest.

My takeaway: the role of CGRP is complex and these new preventives may be the best things to enter the migraine treatment space, but do not jump into prescribing them just because they are new and look good. Think twice. If you use them in a patient, okay, but be cautious and critical about which patients you use them in terms of comorbidities and known unknown safety data in certain populations.  

See early clinical data on Aimovig in a retrospective 6-month review by Lawrence Robbins, MD. 

-Reported by Angie Drakulich 


*Quotes and comments are paraphrased for clarity and style. Commenters’ disclosures may be found on the AAPM35 speakers’ website; updated March 18, 2019.

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