CGRP

1 September 2021

Is This Why Aimovig Won’t Work For You?

James Discoveries & Stats, Medications 0

Aimovig (erenumab) has been a great help for many migraine patients, but not all. Do we know of any reasons why it doesn’t work with some people?

Different medications - problems together?

A good doctor doesn’t want to randomly throw medications in your direction, trying on after the other. A good doctor knows which drugs have good scientific evidence behind them, and if possible which seem to work best for a patient like you – perhaps someone with your symptoms, or your lifestyle, or your medical history.

Now we all know that each person is very different and complex, so we will never type in “10 facts about Me” and have the computer spit out the perfect treatment. But we do have some clues once in a while that help us choose one treatment over the other.

Last year at the 62nd Annual Scientific Meeting of the American Headache Society, a report was presented entitled “CGRP Monoclonals: Efficacy, Side Effects, and Switching”. It attempted to start answering questions about which CGRP related medications were good for whom, and whether or not a patient should consider switching. Another concern is that more side effects were showing up in the real world than had shown up in clinical trials (not uncommon, but something to watch).

There were a couple of interesting notes in particular regarding erenumab, brand name Aimogvig.

First, and not surprisingly, patients with “moderate or severe refractory chronic migraine” were less likely to be helped. That is, those with significant chronic migraine that has not responded to several other common treatments. However, if patients had “mild refractory chronic migraine”, the medication may help.

The second predictor that Aimovig may not work was that the patient was taking opioids.

Opioid medications have helped many migraine patients, but must be used with extreme care because they are notorious for making the migraine condition worse. Occasional or very temporary use may be helpful for pain, but there are usually better options.

So for some reason, patients taking opioids were less likely to benefit from erenumab. This raises an interesting question – if patients stopped taking opioid medications for several months, might they be able get more benefit from Aimovig? Or, if they stopped taking opioids upon starting Aimovig, would symptoms improve several months later?

For the average patient, the study found that most patients could tell after a couple of months if Aimovig was going to be worth it for them. (A good rule of thumb for most treatments is to try them for three months.)

And what about trying a different but similar medication? In this small study, there did not seem to be a general benefit – but remember, for an individual, it may be worth it. The study did note that some patients did switch because of financial reasons, and “more than half of the patients did well”.

17 June 2021

Big News for Nurtec ODT (Rimegepant)

James Medications, News 0

Last month it was announced that the migraine medication Nurtec ODT was approved for the preventative treatment of episodic migraine in adults. This is big news – but you need to understand a little bit of background.

Nurtec ODT, or rimegepant, is one of the new medications that targets CGRP. There are a number of different treatments that are emerging related to CGRP (calcitonin gene-related peptide). And researchers have been investigating which treatments might be better for prevention, and which may be better to take to stop a migraine attack as it happens.

Rimegepant is in the “gepant” class (hence the last part of its name), a CGRP receptor antagonist. It has been noted for a while that the gepant drugs tend to work very quickly – excellent as an abortive drug to take during a migraine attack. And when Nurtec ODT hit the market, one of its selling-points was that it came as a a fast-acting orally disintegrating tablet – ODT.

But while these drugs have been shuffled down into either the “preventative” or “abortive” category, the question has remained – is it possible that some may be effective as both? In the case of rimegepant, researchers noticed that it tended to have a more sustained effect than some other CGRP related medications. So it seemed like a good candidate for a preventative.

And it seems that this is the case. This from the Biohaven Pharmaceuticals press release:

This new approval makes NURTEC ODT the first oral CGRP antagonist approved for the preventive treatment of migraine, and the only migraine medication approved as a dual therapy for both the acute and preventive treatment. NURTEC ODT is approved for acute treatment in all eligible adult patients with migraine, regardless of the number of monthly migraine days.
FDA Approves Biohaven’s NURTEC® ODT (rimegepant) for Prevention

For abortive use, the medication is taken as a 75mg dose. Because of the sustained effect, only one tablet is taken within 24 hours.

For preventative use, it’s the same – 75mg, once every other day.

Not only does Nurtec ODT have a good safety record, it will be very attractive for patients who are looking for a preventative, especially if they don’t like to take a number of pills every day. Of course, you do have to find a way to remember to take it every other day – but migraine patients do learn to be organized!

So this is big news. We’ll see if other CGRP related medications also cross the line from one type of medication to another. Meanwhile, many migraine patients who are experiencing a lot of migraine symptoms in a given month will be looking to see if Nurtec ODT is right for them.

For more information:

30 March 2021

The Brain Prize 2021 (video)

James Discoveries & Stats, News 0

Each year, the Lundbeck Foundation in Denmark awards “world’s largest brain research prize” to one or more researchers who have done important research on – you guessed it – the brain! And this year, the prize is bringing more attention to breakthroughs and continuing research in the field of migraine treatment.

As many of you know, the connection between CGRP in the body and migraine has become a major focus of new treatments, leading to the development of many new medications that are already on the market. The four winners of this year’s prize, from four different countries, were involved in that research. This presentation of the Brain Prize for 2021 gives each researcher a chance to share about the importance of this research, so I don’t want you to miss it.

The winners were:

Lars Edvinsson (Sweden)
Peter Goadsby (Australia)
Michael A. Moskowitz (USA)
Jes Olesen (Denmark)

Now, here’s your chance to listen to the presentation, and hear from these four important researchers. (If the video isn’t visible below, see the video here.)

24 November 2020

Emerging Treatments and Sleep

James Discoveries & Stats 0

Research from the past few years had led to a sudden influx of new pills and injections for migraine, with many more under investigation. But there could be an interesting connection between some of these treatments – your body’s regulation of sleep patterns.

Anyone with migraine will immediately know the connection if we say the words “sleep” and “light”. Sleep is a classic “abortive treatment” for migraine. Changes in sleep schedule are a classic trigger. For many, light patterns and flashes may trigger an attack – and once an attack starts, bright light is the last thing you want!

All this is related to your body’s “clock”. Except that it’s not really that simple. Although you could say that there’s a “master clock” in the hypothalamus, there are also many individual clocks. Some are trying to “sync” with their environment (light plays a big role in this). Others seem to have a mind of their own.

We usually think of the 24 hour clocks, but there are also yearly (circannual) cycles. Cluster headache patients are especially aware of certain rhythms that help explain the “clusters” of these terrible headaches.

Not only are we just beginning to understand how the body regulates all these things, we are really just starting to study these rhythms in migraine patients (and we have a lot to learn about cluster as well). So we have a very long way to go!

But Dr. Philip Holland of King’s College London is a lead researcher who is noticing an interesting connection between the body’s clocks and recent research into migraine treatments.

If you’ve been watching the news, you know that drugs acting on CGRP (calcitonin gene-related peptide – a peptide which occurs naturally in the body and is linked to the migraine chain-reaction) are all the rage. You may also know that there are many upcoming treatments targeting PACAP (pituitary adenylate cyclase-activating polypeptide) are being researched.

So – more drugs and injections. But one thing that CGRP and PACAP have in common is that they’re related to sleep regulation. PACAP works with light to help the function of the hypothalamus clock.

What if sleep patterns could tell us which drugs would work the best? Or what if, instead of developing new drugs, we could find natural ways using light and sleep schedules to minimize or eliminate migraine and cluster headache?

Of course, as we know, these behaviours are already being studied and used to fight headache. What’s new is that we’re starting to see how sleep/wake schedules work in the chemistry of the body. But emerging research is perhaps pointing to the fact that we need to pay more attention to light (think especially of how we use screens, or how working “by the clock” instead of “by the sun” effects us) and our sleep patterns.

By the way, we mentioned Dr. Holland. He is a runner-up in this year’s Medical Research Foundation Emerging Leaders Prize. Read more about the research he is doing at the link above, or at The Migraine Trust here. One of his recent papers can be accessed here: PACAP in hypothalamic regulation of sleep and circadian rhythm: importance for headache (pdf).

28 September 2020

Aimovig after Concussion?

James Discoveries & Stats, Medications 0

Now that several CGRP related medications are on the market for migraine, researchers are interested in finding other uses for the same drugs (even to fight COVID-19). One case in point is the use of Aimovig (erenumab) for headache from a hit in the head.

There are a series of different types of headache that are due to head or neck trauma. Under the heading of “Acute headache attributed to traumatic injury to the head“, the International Classification of Headache Disorders 3 points out that the common definition is a headache that starts within 7 days of the injury, although this is “somewhat arbitrary”, because there is some evidence that the headache could start up to three months later. The problem is that, the longer the interval, the harder it is to connect the headache with the injury.

Millions and millions of head injuries happen every year, so this is a very common issue. A concussion is really a type of brain injury, and there is still a lot that we don’t know about how concussions affect the body (although we’ve learned a lot in the past 20 years).

So from this small initial study, how did Aimovig measure up when it comes to post-traumatic headache (due to mild traumatic brain injury, or concussion)?

It should be noted that these patients were all women, and had suffered from their headaches for over a year (to several years). They had also already tried at least one other daily preventative for headache. So this is not a case of someone with a bit of a headache a couple of weeks after a fall – these are ongoing, difficult cases. And the headaches were moderate to severe.

Taking erenumab, the patients found that, on average, the pain decreased by about half. All five patients were able to stop taking at least one other medication. Four out of five patients continued taking erenumab after the study was completed. But even better, patient #5 stopped taking it because their headaches disappeared completely.

There were no serious side effects, though three patients did have some constipation.

It’s a small study, but for challenging headaches like these the results look good. It may be that other CGRP receptor blockers will also have a wider application for headache treatment.

For more, read the study abstract here: Use of CGRP receptor blocker erenumab in the management of post-traumatic headache: a case series of 5 women