CGRP Antagonists: Not for Everyone? Experts Weigh in…

When it comes to the new migraine drugs, such as Aimovig, Ajovy and Emgality, we can say, “So far so good”. Positive clinical trials, minimal side effects – there is legitimate hope that this new class of drugs will help many migraine patients.

That being said, specialists and researchers are not without their concerns about CGRP antagonists. So let’s take a quick look at what some of those concerns are.

Why would anti-CGRP drugs be a problem, if they fight migraine? CGRP seems to play an important role in sending pain signals. Lessening migraine symptoms by inhibiting CGRP seems to be working well for many people.

But here’s the catch – CGRP is in your body for a reason. If we lower CGRP levels, what will that affect? Our knowledge is limited, but it seems that CGRP has a wide range of important functions in the body. And the trials done so far are fairly short-term. What will the long term results be?

As Dr. Lawrence Robbins points out, “We will have a better feel for the true risk in 10 years.” Yes, but meanwhile?

Here’s the big challenge. Which patients will most benefit from these new meds? No one wants to spend more than is necessary – what if a cheaper treatment works better? And what if some patients have a higher risk of problems from anti-CGRP treatment?

Headache specialist Dr. Andrew Hershey wrote:

With the ongoing development of 4 different antibodies targeting the CGRP pathway, it will be difficult to determine whether unique patient populations will have a response to a specific drug or whether one agent is superior to others. Furthermore, many patients will probably still have a response to standard multidisciplinary treatment that is less costly in patient and provider time and dollars.”

Promise and Pitfalls of Preventing Migraine With CGRP Inhibitors

As we’ve already discussed, the clinical trials up to this point haven’t brought any major issues to light. But there is good reason to continue trials, and watch for problems.

Based on the science we have to date, what are the experts concerned about? What types of risk, or what types of concerns are they expressing? Here are a few of the top ones to watch for over the next few years:

• Cardiovascular concerns: CGRP plays an important role in the cardiovascular system. For example it is involved in the dilation of blood vessels. Could long term use contribute to cardiovascular problems? The trials generally haven’t included groups at high risk. This is probably the biggest one specialists are watching for, and some may be reluctant to prescribe CGRP antagonists to those already at high risk for hypertension.
• “Antidrug Antibodies and Immunoallergic Hypersensitivity”: Without getting into the details, this means that a drug can have a long term effect of causing unwanted immune responses, and/or the drug may become less effective as time goes by.
• Hormones: Could these drugs interrupt proper hormone function? Specialists are especially watching those with thyroid problems, and also growth in children and adolescents (these drugs are only approved for adults for now).
• Gastrointestinal disturbances: Could anti-CGRP drugs have a bad effect on your gut? Doctors will be especially watching those who have recently had ulcers or who have irritable bowel syndrome.
• Pregnancy: Or, trying to get pregnant. Could CGRP interfere with pregnancy?

Again, we don’t have all the answers yet. These are concerns based on what we know about CGRP in the body, but there simply isn’t enough evidence to know the effect that these new medications will have, particularly long term. Hopefully, these issues will be minimal – or, in many cases, non-existent.

Some doctors may consider prescribing anti-CGRP medication for a time, and then having patients take a “drug holiday” for a while. Some may be hesitant to prescribe the drugs to those with cardiovascular or gastrointestinal problems.

Consider the risks – but remember, at this point, the risks seem to be small for most of us, especially if we’re not taking these drugs long term, and if we’re not already in one of the high risk groups above.

The question is not whether or not you should get the best possible treatment. The question is – what is the best possible treatment for you? Some patients will still find other treatments and combination treatments to be far superior and far cheaper than the new anti-CGRP drugs. Others will be helped by medications like Emgality, who have not been helped by other meds in the past.

As Dr. Amy R. Tso and Dr. Peter J. Goadsby wrote in 2017

An important task will be to attempt to identify patients more likely to benefit so personalized therapy can begin to offset the cost of the treatments by minimizing the number of patients treated who have no useful response.

Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention?

For a summary of some of the challenges and concerns when it comes to this new class of drugs, check out Promise and Pitfalls of Preventing Migraine With CGRP Inhibitors. For a longer and more technical article for specialists, with many questions that may need to be answered, go to At Stake: The Possible Long-Term Side Effects of CGRP Antagonists.