CGRP inhibitors

7 July 2022

Did You Quit Your CGRP Preventative Too Soon?

Typically, it seems to be a good idea to try any new treatment for three months. But a new study from Italy is suggesting that some patients may be quitting certain treatments too soon.

In this case, we’re talking about CGRP inhibitors that are used as migraine preventatives.

The study was presented at last month’s annual American Headache Society meeting. The study followed patients who were taking anti-CGRP medication for 48 weeks (about 11 months). The overwhelming majority of patients did indeed respond to the medication within 12 weeks. But depending on the medication, between 7.6% and 15.5% responded in weeks 13-48, the median time of response for the “late responders” being 20 weeks, or about 4.5 months.

Studies like this, though preliminary, raise some interesting issues. Dr. Deborah Friedman (from the University of Texas Southwestern Medical Center), quoted in an article in Neurology Today, gives her response to some of the online chatter that’s been happening:

There are colleagues of mine who said anybody who would keep somebody on a medication that didn’t work longer than three months, it’s unethical. Well, I keep my patients on it for four to six months and that’s what we did with Botox, because I’ve seen people respond late.
Dr. Deborah Friedman

Unethical? Why unethical?

Think about it. Even if there are a few people who may respond late, your chances of responding to the medication do significantly drop after 12 weeks. So if every patient is now put on a trial of 20 weeks or more (some are suggesting 6 months to a year), the drug company selling the product certainly benefits. The insurance company may not be so sure. And most of the people taking the medication for those extra weeks will never benefit from it, and so are only dealing with any side effects with no benefit at all. That’s the cold number crunching.

But the fact remains that some patients may be missing out because they’re only trying the medication for 12 weeks.

All right then, is there a way we could identify those patients – the ones that will benefit eventually – thus improving the odds?

The study has perhaps started to point the way. The researchers did note some tendencies among the late responders:

More likely to have a higher average body mass index
Slightly less likely to have one-sided pain with allodynia (more on this below)

Of course, this works both ways. If you have one-sided pain with allodynia, you may be a little more likely to benefit from an anti-CGRP preventative. Because basically the late responders were simply a little more like the non-responders.

This is a long way from a way to identify which patients will respond late. But what the study does tell us is that we should be looking closer to find out how we can identify those patients – it shows us that there may be a way, eventually.

Right now, it’s probably best to have a good relationship with a specialist you trust, and let them help you decide if it’s worth it to try your medication (or other treatment) for longer. They know you best, and know your medical history.

To delve further into this topic, check out the article at Neurology Today by Thomas R. Collins: Late Migraine Responses Seen for Anti-CGRP Therapy

Also the National Headache Foundation has put out a video on the optimistic side, explaining this study:

22 October 2020

What Is Surprising Us About The New CGRP Preventatives?

James Discoveries & Stats, Medications, News 0

Can you believe it? It was in the spring of 2018 that Aimovig (erenumab) was approved in the USA. My! Time flies!

Really, all the CGRP related drugs are still extremely new, when it comes to prescription drugs for migraine. Long term trials are still a future hope. And we’re just starting to guess at some trends that we may be seeing from patients.

But what are some of the trends we’re seeing? Let’s take a moment to talk about them, and you can comment if you’ve had a similar of very different experience.

(1) For many, these drugs are working better than expected!

First, the (very) good news. For many patients, these CGRP inhibitors are working better than the clinical trials even led us to believe.

As drug companies rush to market new migraine drugs, we expect to see headlines that use phrases such as “life-changing!”. But in the case of drugs like Avojy and Aimovig, this does seem to be the case with many patients – a very significant improvement in their symptoms.

And these are not always “just any” patient. These are patients who have not had a lot of success with other medications.

So there are good reasons to have a lot of hope that these new drugs will help many more people around the world in the next few years.

(2) Sometimes these drugs are less effective after a while.

This is a biggie. Reports are coming in that, for many patients, the benefits tend to “wear off” after a while.

Will switching to another CGRP preventative help? It’s very possible, and it’s not at all a surprise that you may need to try more than one before you find the right fit.

But this is one that researchers are going to pay a lot of attention to in the next few years. Which patients are having this issue, and why? Will some CGRP preventatives work better than others? Even if they’re not as beneficial as they were in the first few weeks, do they still provide significant benefit? What’s your experience?

(3) Side Effects

Any surprises with side effects? Side effects are not a huge problem for many patients, but it is starting to sound like constipation is an issue for some, especially with Aimovig (and in this case, switching may provide significant benefit). It seems that it may be more likely to make constipation issues worse if you already have a pre-existing condition.

In a recent discussion published in The American Journal of Managed Care, two neurologists pointed out some of the other side effects they’re seeing – “. . . a worsening of Reynaud syndrome, fatigue, hair loss, sexual dysfunction, and in women, some reports of irregular menstrual periods.”

Again, discussing side effects shouldn’t make it sound like patients are running away from these medications in droves because they’re all having major problems. Side effects may be rare, but we have to keep an eye on them because certain patients may be more prone to certain side effects than others.

If you’ve been taking a new preventative, such as Vyepti, Aimovig, Ajovy, or Emgality, how long have you been on it? What has your experience been? Anything you might share could be a help for our community.

7 November 2019

Very Different “CGRP Drugs”

James Information, Medications 0

With our current obsession with the four magic letters, “CGRP”, and the CGRP related drugs that are now hitting the market, many people have not realized that there are two very different types of CGRP drugs out there. So here’s a quick description to get you up to speed.

What is “CGRP”?

CGRP (calcitonin gene-related peptide) refers to a peptide, a type of amino acid, that is naturally in your body. A lot of study is currently being done regarding the connection between CGRP and pain. It does seem to play a key role in the way your body responds to pain, inflammation, and migraine in particular. It may be that problems with CGRP function may cause you to become overly “sensitive”, leading to chronic migraine and other chronic pain conditions. However, we still have a lot to learn about how it works.

Blocking CGRP?

So if we somehow block CGRP, could we lessen the symptoms of migraine, or even stop migraine in its tracks? Well, that does seem to be the case with some people. We could either do this in a preventative way – that is, take a medication regularly to keep CGRP under control. Or perhaps we could use it to stop a migraine attack that has already started – that is, use it as an abortive. But how do we actually lower levels of CGRP?

CGRP Inhibitor

What if we could target CGRP itself? That’s the goal of the new preventative drugs that are hitting the market now. They’re called CGRP inhibiting monoclonal antibodies (mAbs). These include erenumab (Aimovig), galcanezumab (Emgality), fremanezumab (Ajovy), and eptinezumab. These are taken by injection either monthly or quarterly in order to lessen migraine attacks and symptoms. You’ll notice that these drugs use mAb in their names.

CGRP Receptor Antagonists

“Inhibitor” and “Antagonist” have a similar meaning, but you’ll notice that in this case the target is slightly different. Instead of targeting CGRP itself, we go for the CGRP receptor. These drugs work very quickly, but they’re not getting to the market as fast because they’re being carefully studied to make sure adverse reactions are minimal.

However, because they are “fast” they should make great abortives – something to take when the migraine attacks hit. These are the “gepant” drugs – such as ubrogepant and rimegepant. Also called a receptor “blocker”, the mechanism is complicated but you can think of it as another way to keep CGRP from functioning, hopefully lessening migraine symptoms during an attack.

And then…

There are several other types of migraine drugs on the way, each with a different way of attacking migraine. These include 5-HT1F agonists, and anti-PAC 1 drugs. We’ll try to talk more about these in the future. But the idea is to stop the migraine chain-reaction so that symptoms are lessened or stopped. Ideally, the closer we get to the “source” of migraine, the more we’ll be able to stop it altogether.

4 November 2019

Combining CGRP Inhibitors with – Botox

James Medications 2

Now that some of the new CGRP inhibitors have hit the market, studies are beginning to see how they might work with together with other treatments. At the University of Utah, the treatment includes Botox (onabotulinumtoxinA or ONA) and Aimovig (erenumab).

The patients trying the combination treatment, in this case, had already tried 3, 4, 5, or more treatments without success. Many also suffered from depression, anxiety, insomnia, and other co-morbid disorders. Most, though not all, were women.

Both ONA and the CGRP inhibitors such as Aimovig are given by injection. Botox every 12 weeks, Aimovig every 4. (The upcoming drug eptinezumab is meant to be given every 12 weeks, so it would be interesting to see how that works with ONA as well.)

The benefits of ONA are known to be inconsistent over the 12 weeks between treatments. In other words, there may be days, especially near the end, when it’s not helping the way it did at its peak. So combining it with another medication may help the situation.

In this study, which is small but ongoing, the results were not spectacular but they were promising for some patients. Slightly more than half of the patients did see significant improvement with the combination. The bulk of the rest found no improvement, although 18% found that their “headache burden” actually got worse.

So once again this is a treatment that may be a tremendous benefit to some patients. And remember, these were generally patients who have tried several other treatments without success.

One of the biggest challenges when it comes to combination treatment, and combination treatments that work with many but not all patients, is insurance coverage. It is in the best interest of insurance companies in many cases to see stable improvement of migraine symptoms. But convincing them that this is the way to go may take time.

We would be interested to hear your comments if you have tried any of the new CGRP inhibitors in combination with Botox treatment. Leave a comment!

19 June 2019

“First FDA-approved drug that reduces the frequency of attacks of episodic cluster headache”

James Discoveries & Stats, News, Treatments 0

Earlier this month in the USA, the FDA approved Emgality (galcanezumab) for use with episodic cluster headache. This is a big step for CGRP inhibitors, which have shown promise for treating both migraine and cluster (for example, see this article about Ajovy).

As the official Emgality site states:

For adults with episodic cluster headache: Emgality can help reduce the number of weekly cluster headache attacks that occur during a cycle
Emgality.com

As mentioned before, CGRP inhibitors have shown promise for episodic cluster headache treatment, but the treatment of drugs like Emgality is far from a magic cure.

While most of the articles about the recent FDA approval point to the 8.7 fewer attacks per week during a cluster cycle, there is more to the story.

Patients experienced 8.7 fewer attacks, with only 5.2 fewer attacks with placebo. Significant enough to show that Emgality seems to be doing something, but by no means a silver bullet.

But that was in the middle of the trial, which was an 8 week trial. After two months, the difference between Emgality and placebo was even less – a difference which some say “is no longer statistically significant” (see Galcanezumab Offers Help for Cluster Headache and Migraine).

It is good news that cluster patients have something else to try – and we hope that Emgality will help some. But much more needs to be done to help cluster headaches. Sadly, this is only a small step toward better treatment.