S5 E4: Exploring new anti-CGRP treatments for migraine

Exploring new anti-CGRP treatments for migraine

Series 5, episode 4

Heads Up is the award-winning podcast series on all things headache, brought to you by the National Migraine Centre.  Produced by leading headache doctors, it’s the trusted source of information and support for all those affected by migraine and headache.

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Transcript

00:00:00 Welcome to the Heads Up podcast, brought to you by the National Migraine Centre, the only UK charity treating headache and migraine. Visit our website to book your appointment with a world-class headache doctor, wherever you are in the UK. There is no need for a referral. You can refer yourself. Our headache specialist doctors are looking forward to helping you soon.
00:00:34 Dr Katy Munro
Hi everybody and welcome to this episode of Heads Up podcast. We are now in Series 5 and I hope you have found the other episodes useful. Feel free to dip back into any of them and re-listen. We have done an episode on this topic before, but we thought today we would do an update for you on the new CGRP medications, so my friend and colleague Dr Becky Walker is joining me today, and we’re going to update you on the state of things with these amazing new medications, which specifically are designed to help people with migraine. So Becky, do you want to introduce yourself?
00:01:14 Dr Rebecca Walker
Hi Katy. Thank you so much for inviting me to be on your podcast. I’m really very excited to be here and helping you with this update. For our listeners, a little bit about me, I am a GP and I’ve had an interest in migraine and headache medicine for a long time, and jumped at the chance of joining you in the team at the Migraine Centre in in 2021 and I’ve been working as a headache specialist with you ever since. In my GP work, my patch is Devon, and I work with David Kernick at our local integrated care headache service. And another big passion of mine is menopause care. So I work with a group of menopause specialist GPs at Mila Health looking after women going through this often challenging transitional time.
00:02:00 Dr Katy Munro
I think it’s really lovely actually. We’ve got a lot of headache specialists on the team now and many of them are very interested in perimenopause and menopause care. And so I think that because a lot of the women we see are in that stage of their life may not always realise it, people in their mid to late 30s and into the 40s. And I know personally I didn’t recognise it, but it was a time when I started getting migraine attacks, having never had them before. So it’s really great I think, we’re all very focused on working holistically and talking to women about hormones as well.
00:02:39 Dr Rebecca Walker
And trying to anticipate these changes rather than reacting or having a very reactive approach, which is often when things have got really quite debilitating. And life has been quite significantly impacted, so yeah.
00:02:50 Dr Katy Munro
Definitely. And so, hormones. We have had some episodes of the podcast on hormones and I think we may do one again soon. Another one on the perimenopause. But today we’re focusing more on the CGRP medications. And these fall into two groups at the moment – injectable forms and tablet forms. So Becky, do you want to explain what CGRP stands for and why? Why are we talking about it? What is it?
00:03:21 Dr Rebecca Walker
So this is a really interesting — I’m going to call it a protein just for ease of terminology. We’ve known about CGRP, which stands for calcitonin gene-related peptide for some time, but it was back in the late 1980s when Professor Goadsby first really identified its role in migraine pathways. And this then formed the basis of further research into medicines that might specifically target migraine. So it’s been a very exciting time over the last couple of decades.
00:03:54 Dr Katy Munro
Yeah. And Professor Goadsby I know also works with Lars Edvinsson and they and their colleagues did a rather groundbreaking study by infusing CGRP into people and seeing if it caused migraine attacks and it did. I mean, what kind of — volunteers to go and have a migraine attack being forced upon them? But that was a very important discovery, I think, to know what kind of things we could do to block that neuropeptide or protein, that’s produced and seems to be significant. But of course, it’s not the only one, is it? There are lots of other ones that may be as significant. But research is going on into those, so they have names like vasoactive intestinal peptide and substance P. And what we think happens is that these kind of neurochemicals are produced in the brain, but they cause the blood vessels to dilate. That’s one of the secondary effects of them and this seems to be quite significant in generating migraine attacks. So, hopefully lots more research will be going forwards and the more we know about why people get migraine and what the underlying mechanisms are, then the more we can help and not have to borrow medications from other conditions, which is what we’re largely doing at the moment. You know, trying to prevent migraine with things that were also for blood pressure or also used for epilepsy or also used for depression. So it’s really great.
00:05:37 Dr Rebecca Walker
I was just going to say, Katy, just in terms of borrowing other medicines, we do find that side effects can be quite problematic with lots of the tablet medicines that we have because they’ve been designed for other indications and we’ll talk in a bit about the side effects associated with anti-CGRPs. They seem to be really low and they should be really well-tolerated medicines.
00:05:58 Dr Katy Munro
Yeah, I agree. Yeah. So we at the National Migraine Centre, we were lucky that we were able to start prescribing these back in 2019, but they have been available on the NHS now. So let’s talk about the CGRP monoclonal antibody injections. So there are four now available. Do you want to just outline what those are, Becky?
00:06:25
So there are three that are self-injectable medicines. So these are medicines that are given once a month with an auto-injector and I’ll use the brand names because they’re probably easier to say and easier to remember. They are Aimovig, Ajovy and Emgality. Ajovy’s a little bit different because you can give three injections as a loading dose at the start of the three month course. So those are the three that have been around for longest, still a relatively short period of time. And then very recently, just this year, NICE have just approved to eptinezumab or Vyepti, which is an intravenous infusion that’s given in a hospital setting for about thirty minutes and that lasts for three months.
00:07:08 Dr Katy Munro
Yeah, that’s a really exciting new one. We haven’t had any experience of using that, but I know they are beginning to use it in some secondary care headache clinics. We’ll talk a little bit about that. Talking about Aimovig and Ajovy and Emgality: Aimovig targets the CGRP receptor, where Ajovy and Emgality actually target the neurochemical itself. In your experience, have you noticed that there’s a great deal of difference in whether patients respond better to one or the other? I get the feeling that they’re much of a muchness and we don’t have any way of knowing which one will suit an individual patient, would you agree?
00:07:58 Dr Rebecca Walker
Absolutely and I think that’s borne out in the literature that we have available. So there haven’t been any studies that have compared these medicines head to head. So the analysis has looked at basically comparing the studies and the outcomes appear to be the same, and certainly our real world practice experience suggests that that’s the same. There doesn’t seem to be one that’s preferential over the others. So yeah, I agree with you.
00:08:23 Dr Katy Munro
I was going to say it does sometimes happen that somebody will not do so well on one, and then we’ll change to a different one and they sometimes do better. So I think as we advise with the triptans, it’s probably worth just not giving up if one doesn’t work for you. If you are able to get a trial of a second one, that may be useful.
00:08:42 Dr Rebecca Walker
And I think being a charity working outside NHS restrictions and commercial agreements, we are in a fortunate position of being able to offer our patients all three, whereas I think quite often NHS trusts are bound and can only offer one of these treatments.
00:09:03 Dr Katy Munro
Yeah. So in the NHS obviously we have NICE which is the organisation which decides what things are going to be available through the NHS and all of these have been approved by NICE and there are some strict criteria for the NHS to use them. So I was just double-checking my memory. So it’s much the same for all of them, for the self-injected ones. You have to have had four or more migraine days a month. You have to have had at least three preventive drug treatments which haven’t worked successfully for you, and there’s usually some sort of commercial arrangement between the pharmaceutical companies and the NHS to make these affordable to the NHS. And then they suggest that these drugs are stopped after twelve weeks if their migraine frequency hasn’t reduced by at least 50% if they have episodic migraine and at least 30% if they have chronic migraine. And just to remind people, the difference between episodic and chronic is really a number, so if you’re affected on more than fifteen days in a month with eight of those being migrainous, then you’re classified as having chronic migraine. And if you’re affected on less than fifteen days in the month, we call it episodic, slightly arbitrary numbers, I think. We have to have some way for research studies to be looking at comparable patients and so they’ve picked the number fifteen. We clinically often talk about high frequency migraine, don’t we, people who are having some ten-fourteen days, but that’s not an official term.
00:11:02 Dr Rebecca Walker
So what I think a big stumbling block for people when they’re sitting with their GPs trying to work through the process on this journey to try these new medicines, is that what constitutes a trial of a tablet medication and why they have to do this? I don’t know whether you could expand a little bit on what a treatment trial is, on what a trial of these medicines is?
00:11:24 Dr Katy Munro
I think it’s a real tricky one, that one, isn’t it? Because NICE very kind of vaguely puts that you have to have tried at least three preventive drug treatments. But we know from our listening to our patients that sometimes people will have been on something for about two weeks and given up on it, they’ll have had a tiny dose and then not been given very good advice about how to use that preventative drug treatment. So what we would say is to have a good trial of a preventative drug, you need to be on the maximum tolerated dose for a minimum of three months. That’s what I generally say anyway. So the maximum tolerated dose implies that if you get to a dose where you have side effects then you go down one dosage step and stay on that dose for a minimum of three months. You don’t just throw out the baby with the bath water, so to speak.
Some people can’t take certain medications, so people with asthma can’t take the beta blockers, so that excludes them from trying those. But I have been hearing from some patients that they’ve been asking in secondary care headache clinics and have been told, Oh well, you haven’t tried that high enough dose or you haven’t tried four or five different drug treatments, so one of the problems, I think is that all over the UK, individual hospital trusts are making up their own guidance as to whether or not they will offer these. Are you finding the same?
00:13:08 Dr Rebecca Walker
Absolutely. And so you know, someone in the east of England might, as you say, have to try five. For someone in the southwest it might be very adherent to NICE recommendations, which is three. It does seem to vary and how far patients are pushed on these medicines again seems to vary. But I think that advice that you were just outlining is really important about persevering, making these changes gradually, because migraine brains take a long time to adjust to the medicine changes and to medicines. But I think the key is that often support is needed, isn’t it, on these journeys. And I think that’s often what’s lacking — support.
00:13:52 Dr Katy Munro
It is frustrating for patients, isn’t it? And I had a gentleman the other day who had been over the years, had been on many, many different preventives, but he was saying to me, why is it that this treatment, which is specifically for migraine, I can’t access it and I’m being told I need to take these other borrowed medications, as we were saying earlier, and I really feel sympathy for that. You know, I think it’s really, really hard because we have to balance that against the pressures on the NHS at the moment and we know that funding is an issue and staffing is an issue to set up access for these injectable therapies. The hospital trusts do have to put in place perhaps a new clinic or a headache nurse or some sort of systems. And some are much quicker than others at doing that, I think. We’ve had some who’ve been providing these right from the get-go as soon as they were licenced and as soon as NICE was saying that they were approved, and others who are still not quite on board. They have to be prescribed by a headache specialist and there aren’t enough headache specialists in my opinion in the UK at the moment or probably globally. There need to be more people interested in headache. But the other constraint is that some hospital trusts are offering these to patients for a year and then saying now you have to have a break, you have to have a three month break. And this again is variable, isn’t it? So I’ve had some patients who say, oh, no, I’m so good on it that they said I can just carry on. And I’ve had others who’ve been told very firmly, you have to have three months off it and see what happens.
00:15:42 Dr Rebecca Walker
That’s really interesting. I’ve not come across anyone that’s been allowed to stay on it. Actually, my experience is that most of the time there is this twelve month cut off and then it’s re-assess after three months to see how much your migraine has returned.
00:16:00 Dr Katy Munro
And what is your experience of what patients are reporting when they come off it for that three months?
00:16:07 Dr Rebecca Walker
It’s variable. People do enjoy a period of remission, I think, but quite often we see migraines starting to come back after that two or three to six months.
00:16:16 Dr Katy Munro
Yeah, I think that’s backed up in the studies, isn’t it? And I’m talking to consultants around the UK. A lot of them are saying, well, you know three to six months later, migraine attacks are creeping back again, which is really frustrating, isn’t it? Because then what we would hope is that the brain quietens down, irritability settles, the threshold for having attacks moves further away and people experience a long period where they don’t have migraine attacks
00:16:48 Dr Rebecca Walker
But that might be the case, it might just be that period might be two or three years. I think we’ll know in years to come. It might just not be quite long enough, and certainly I think if you put this into the context of a woman going through the transitional change of menopause, we know that that transitional process can take years and years and years and so similarly, it might well be that settling the migraine machinery also takes a bit longer than twelve months.
00:17:13 Dr Katy Munro
I think that’s a really good point actually. And I think generally a migraine does tend to improve with age, doesn’t it? And so hopefully – I say to people, even if they’ve had a break and things have returned, they’ve got these episodes of migraine again coming back. It’s worth keeping on and then maybe having another try at coming off these medications. The trouble is, they haven’t been around for long enough for us to know really what the long-term benefits or possible side effects might be. So yeah, a lot of ongoing research I think to see what’s the optimum length of time to be on them and all those sort of questions.
00:17:58 Dr Rebecca Walker
They do seem to be different to the tablet medicines that we have there and I’m echoing Jess from your previous podcast, I say that rather than patients saying “how long do I have to be on this? When can I come off?” It is a different conversation, isn’t it? It’s “Do I have to come off, can I not stay on it? I’ve got my life back, I’m working.” It’s so rewarding to look after people who come back and tell you that they’ve gone back to work, that they’re socialising again, they’re exercising again when they’ve been through, you know, maybe years when they haven’t been able to live life to the full because of migraine.
00:18:36 Dr Katy Munro
What percentage of patients would you say respond well to these injectable anti-CGRP monoclonal antibodies?
00:18:48 Dr Rebecca Walker
You always say anecdotal evidence is not evidence, but I have to say that in my time at the National Migraine Centre, I think I probably enjoyed a pretty near 100% response rate with these medicines, which is a big statement but truly, I think that I haven’t had anyone to come back to me to say it’s not… It might not be that everyone has had their life completely transformed, like super responders, but it’s generally people are having enough of an improvement with them to feel like they have got some control back and they’re living life again.
00:19:25 Dr Katy Munro
I would say I haven’t had 100% success with them, so I never like to promise people that it’s going to be a miracle for everybody.
00:19:39 Dr Rebecca Walker
I don’t either.
00:19:41 Dr Katy Munro
I would say again, talking to consultants from the headache clinics around the country as well, I think they’re generally saying about 70% of people get some benefit. Some of those people will be, as you mentioned, super responders where they come in and they they’re almost crying with joy, aren’t they, with relief that suddenly they’ve got their lives back. But there are a number of people who get maybe a 50% benefit. Maybe the pain is half as bad. I gave a talk the other day and somebody afterwards was chatting to me and she said, “I’ve been on one of these CGRP drugs, and although it hasn’t melted my migraine attacks away it’s made the impact go from an 8 down to a 4 and I’m really happy with that. I can function at 4”.
00:20:38 Dr Rebecca Walker
Yes, like that. I would certainly say that so. So yes, I suppose in my professional headache specialist role so far I have not seen anyone who hasn’t had any response to these, but you know, as I say, I’ve got a pretty long career to go and that’s going to happen at some point, but they seem overall to be really beneficial and really well-tolerated.
00:21:00 Dr Katy Munro
So that brings me on to side effects. What kind of side effects have you heard people reporting to you?
00:21:07 Dr Katy Munro
So the most common one is constipation, and I think that came up in your last podcast too, I think that by far and away. We know that CGRP is expressed in the gut as well, so it’s logical that there might be some gastrointestinal side effects with this type of treatment, but the constipation tends to be manageable. It tends to be preferable to migraine for most people who have been battling chronic migraine and often lots of the supportive supplemental therapies like magnesium taken alongside anti-CGRP for improved migraine control can really benefit that side effect.
00:21:46 Dr Katy Munro
I’ve had some people talking about injection site reactions. And is that one you’ve come across commonly as well with sort of redness stinging for a short period of time around the site?
00:21:59 Dr Katy Munro
Yeah. And again, that seems to be manageable.
00:22:01 Dr Katy Munro
Yes. It’s not a game changer that one usually. Although I did have somebody who said yesterday that she did have quite a strong reaction. She was somebody who had Ehlers-Danos Syndrome and mast cell issues and she’s quite sensitive generally to medications and she had struggled a bit with it. Sometimes taking antihistamine on the same day seemed to have helped a few of my patients if they have that little reaction.
00:22:29 Dr Rebecca Walker
Have you had anyone who has discontinued with anti-CGRP therapy because of side effects?
00:22:34 Dr Katy Munro
Very few but yes, possibly one or two. Yeah. OK. Yeah.
00:22:43 Dr Rebecca Walker
And would that be injection site reactions? Would it be for that reason?
00:22:44 Dr Katy Munro
Yeah, injection site reactions or really severe constipation. One or two have had really severe constipation. I think it’s more common with Aimovig. It doesn’t seem to be such an issue with Ajovy and Emgality, and that may be because they work slightly differently. Yeah. But I think in general, the side effects are very much more possible to put up with than having chronic migraine, which is what we’re normally prescribing this for.
00:23:18 Dr Rebecca Walker
I had one lady who mentioned hair loss and I think that is listed in the side effects of Emgality – is it Emgality? I’d have to double check – she said again the improvement in the migraine was such that she wasn’t going to stop and actually nine months down the line, her hair growth had returned, so whether it was a temporary phenomenon, whether it was making the medication, I don’t think we’ll ever know. But it is possible.
00:23:47 Dr Katy Munro
I think it’s really important if anybody is starting on these medications and they have anything happen that they think may or may not possibly be related. There’s a thing called the Yellow Card reporting system for side effects. So if you go on Google and type in “yellow card safety” then you can as a patient or as a professional to report any adverse events. So that may be something big that’s happened to you, or it may be something quite mild, and in that way we gather more and more data about the real world of using these medications. So I would urge and always encourage my patients if they’ve had anything that they think might be related to fill in the details, it doesn’t take very long and it’s a really useful source of information.
00:24:35 Dr Rebecca Walker
Yeah, absolutely. These injections are given every four weeks, do you see any wear off in any of your patients?
00:24:48 Dr Katy Munro
Yes, it’s funny that, isn’t it? So sometimes we do find that patients come back and say in the last week before that, if they’re in week four, “I start to feel that it’s wearing off and my migraine attacks seem to be starting to come back again. Then I give myself the injection. It all settles down for another three weeks and then it wears off again.” Not everybody though, and for some people it just works all the time. I mean our mantra is nothing works for everybody, everything works for somebody and migrate is so individual that it’s really about each individual person finding their own recipe for success, I think. We don’t have any tests. I’ve been wishing that pharmacogenetics would catch up with migraine because I think if we could take a cheek swab, send it off and you know the genetic sequence thing.
00:25:44 Dr Rebecca Walker
Yes, it’s your treatment.
00:25:47 Dr Katy Munro
Yeah. And then to say this will be the one for you. I mean, that’s got to come, I think. But we’re not there yet with it and when it does come, it may transform how we choose medications in all sorts of areas.
00:26:03 Dr Rebecca Walker
That’s really helpful. What do you do? You have any tips for managing that wear off period for people who start to find migraine creeping back in?
00:26:12 Dr Katy Munro
That may bring us on to talking about other CGRP drugs that may become available later. Managing your acute breakthrough migraine attacks in that wear off period I think is just how you would normally manage them and hopefully having your acute rescue remedy handy will mean that you can get through. Anticipating it, I sometimes use things like naproxen, a non-steroidal anti-inflammatory, which is a little bit longer acting than ibuprofen. Obviously people need to be sure that they can safely take these things. But sometimes using that regularly three times a day for a short period of time can just tide somebody over and I offer suggestions about that. I’ve been talking to a lot of fifteen-year-olds lately. GCSEs are coming. They’re sort of saying, “How can I get through my GCSEs without having a migraine attack?” And that sort of short-term use of non-steroidals can be quite handy for them and for people who are travelling or who have to go to a wedding or something like that. Taking a non-steroidal anti-inflammatory for maybe one or two weeks and then when the risky time is gone, going back to their usual intervention can be quite a helpful strategy.
00:27:38 Dr Rebecca Walker
I think something else that’s probably quite important to say is that what people often find is that medicines that in the run up to starting anti-CGRP treatment might have stopped being quite as effective as they used to be for getting on top of their migraine and aborting their migraine attacks like triptans suddenly start working again and I think I hear that a lot as well that triptans start rescuing in the right way again,
00:28:12 Dr Katy Munro
Yeah, I think you’re right. Definitely. I think one of the benefits of the CGRP drugs improving migraine is that people then stop taking the acute medications too frequently. So this thing called medication overuse headache, which is not a very nice term, and I’ve heard people calling it medication survival headache, when you have to take something to get through the day. But if you’re getting acute episodes very frequently, you take your acute medication very frequently. You can actually be aggravating your migraines. So once that is improved by the CGRP drugs, the amount of medication people are taking drops down and then it starts to work more efficiently. So yeah, I think that’s probably what’s happening there.
00:29:00 Dr Katy Munro
Then just to go on to who would you advise these for? So we know they’re licensed for episodic and for chronic migraine, but I’ve been asked do they work for vestibular migraine as well – that particular type of vestibular dizziness where maybe their most bothersome symptom is not headache, but it’s that unsettled, spaced out and dizzy feeling. People saying, “Do they work for brain fog? Do they work because I get lots of aura.” What would you say is your experience of using them for those?
00:29:33 Dr Rebecca Walker
Oh, it’s really difficult. I think there isn’t very much data out there yet on using these medicines for these cohorts of people. I think that will come in years ahead. There is early preliminary observational data certainly from the USA that anti-CGRPs can help with vestibular migraine and not just with the headache symptoms, but also with brain fog and that sense of imbalance that they experience. So I think it’s promising and I would certainly support people with a trial of these medicines to see whether they help with these symptoms. I don’t know whether you agree.
00:30:17 Dr Katy Munro
Yeah, I think I definitely agree with that. I think it’s one of those things where we have to think about migraine as a brain process, don’t we? It’s not just a headache and we’re always banging on about that, it’s not just a headache. I sometimes say, oh, it’s a genetic, whole body, lifelong neurological condition. And if you think about it as that then I think it makes more sense that if you’re trying to block the process that generates migraine attacks, then it will probably help all aspects.
00:30:55 Dr Rebecca Walker
Those symptoms as well.
00:30:57 Dr Katy Munro
It does make some logical sense, but I agree with you. I don’t think the data’s there for us to know 100% whether that’s true. So that’s just my hypothesis really.
00:31:08 Dr Rebecca Walker
I like it, I’ll share it.
00:31:10 Dr Katy Munro
What about children?
00:31:12 Dr Rebecca Walker
So we don’t use these medicines in children yet but there is research going on again I think focused in the USA. I think early mumblings are that they are effective. But at the moment they are very much reserved for last resort treatment when lots of other medicines have been tried because we don’t really yet understand what impact they might have on growth and development. So I think possible in the future, but not at the moment. I think with kids, if you look at the data on preventative treatments for children, actually the most important migraine measures for young people and children are lifestyle measures so looking after sleep, looking after nutrition, looking after hydration, managing stress, all of those sorts of things actually are far more important and probably more effective than the medicine.
00:32:15 Dr Katy Munro
Yes, I agree there’s not enough data on effective treatments for migraine in children, although we do use some of them and they can seem to benefit individual children. And I’m just going to put in a quick plug here for thinking about abdominal symptoms in children, because every time I give a talk I include something about children getting migraine pain in their abdomen, getting tummy aches. And so if any listeners there have migraine and they also have children, do think “migraines” especially as your children come up into the many changes of secondary school, puberty, all of the stresses that go around that, we see a peak instance at fourteen, but I’ve been seeing quite a number of primary school children recently who’ve had pallor, they feel a bit sick from time to time, and they need to go and lie down in a dark room with tummy aches, and then nobody has thought about migraine as the underlying diagnosis. So yeah, that’s my quick plea to think about children.
I wanted to ask you because of your interest and skill and expertise in perimenopause. When somebody comes to you and they are perimenopausal and they’ve had a worsening of their migraine attacks, would you start with hormones first, settling down the hormonal fluctuations with HRT? Or if they’ve tried a lot of other preventers, would you jump into the anti-CGRP drugs? What are your thoughts about those or would you do both?
00:33:52 Dr Rebecca Walker
Possibly both. I certainly think it comes down to individualised care as much as we possibly can and patient choice, obviously with hormone replacement therapy, there’s a lot of counselling that’s involved in working out whether it’s right for a woman and what type of hormone treatments might be helpful. There are definitely women with very hormonally sensitive migraine who absolutely benefit from a nice steady, smooth hormonal state that can be provided by using oestrogen therapy and continuous progesterone therapy and I know that you’ve spoken to Professor MacGregor about that in the past. But then there are some women who might have high-risk breast cancer genes in the family, for example. And actually they really don’t want to take any risk even if it is small with HRT and actually they prefer to focus on management of migraine which you know essentially is an underlying condition that is exacerbated by hormones. I have a lot of women who decide that they don’t want to go through the trials with lots of different preventive medicines, which may have significant side effects, and they do opt for anti-CGRP therapy over and above tablet medicines and they can work very well. So we don’t have any data specifically looking at women with menstrually related migraine or menstrual migraine which comes with, we believe, the drop in levels of oestrogen around the time of the period. But data extrapolated from the original studies into these medicines suggests that these anti-CGRP therapies are effective in reducing the impact of menstrually related migraine so they are a good option for women with hormonally sensitive migraine I think.
00:35:47 Dr Katy Munro
That’s really helpful, isn’t it, because menstrually related attacks are often quite tricky to treat. They can be more severe, they can be more prolonged, and women are often more likely to have issues around the perimenopause if they’ve had menstrually related attacks as younger women. The other group I suppose we haven’t talked about are people who are wanting to start a family or have further children, so pregnancy and breastfeeding. And of course, at the moment, the guidance with these monoclonal antibody injections is you need to stop them at least about six months before you try for a pregnancy because they have a long half-life, so they hang around in the body for quite a long time and we just don’t have enough data to know whether they’re safe. But it does seem, and I think I’m right in saying that, if women are wanting to breastfeed because they’re quite large molecules, it’s thought that they don’t go through into breast milk. And so it’s been quite reassuring that we think they probably are safe, but I think that’s something, if any woman is wanting to become pregnant and then to breastfeed, need to have a good discussion with whoever is prescribing that CGRP drug for them to make sure that they know that up-to-date advice on that, would you agree?
00:37:17 Dr Rebecca Walker
Absolutely. I think again it comes down to the discussion and informed decision with whoever’s sitting in front of you so that they can make the right decision for themselves. We know how debilitating migraine can be and we know how it can rear its ugly head in the aftermath of having a baby. Sometimes the benefits of treatment might outweigh any tiny, tiny, negligible risk. As you say, it’s unlikely that the medicines are passed into breast milk. So yes, a risk-benefit discussion.
00:37:50 Dr Rebecca Walker
Look at who’s in front of you.
00:37:51 Dr Katy Munro
There’s a bit of interest in these monoclonal antibody treatments as to whether they’ll help people with cluster headache. Cluster headache is a different primary headache disorder, probably one of the most severe pains that you can possibly experience, and it comes on extremely suddenly. It’s always one side of the head. It gives a watery red eye, stuffy nose and the onset of pain is very, very quick. And people who have cluster headache tell us that when they have an attack, they want to pace around, they feel very agitated. They may even punch their head or bang their head on the wall. I’ve even had extreme cases of people hurting themselves to try and distract themselves from the pain of cluster headache. Quite a different history from people with migraine, who tend to want to stay still and keep very calm and quiet in a dark room. So anything that will help people with cluster headache is a real step forward because there aren’t that many medications that help. So I think it’s Emgality which is the one which has got a bit of evidence in cluster headache, hasn’t it?
00:39:07 Dr Rebecca Walker
That’s right, yeah. And for episodic cluster headache.
00:39:13 Dr Katy Munro
Yes, I think you’re right. Yeah. So again, episodic cluster headache is where you may have recurring attacks or anything between two weeks and three months, and then you have a long break, hopefully, where you’re back to normal and no headaches are occurring. Chronic cluster headache is where people are getting attacks pretty much all the time, much harder to treat, but episodic cluster headache can benefit, I think, in some people if they are prescribed Emgality.
00:39:47 Dr Rebecca Walker
I suppose the challenge there is accessing it when you need it.
00:39:52 Dr Katy Munro
Yes. Normally if we see people with cluster headache, we do normally encourage them to be under a specialist headache clinic in the NHS for that very reason really, that they can then get quicker access to these things.
00:40:08 Dr Rebecca Walker
Katy, do you know of any centres that are offering immediate or urgent access to Emgality for cluster?
00:40:17 Dr Katy Munro
I don’t particularly, although I do know that Guy’s and Thomas’ have a rapid access cluster headache clinic. The trouble is, with all of the headache clinics, I think they’re all very overwhelmed and the more that people know about these new treatments, the more referrals they’re getting. And with the way that the NHS is at the moment, there are long, we hear it all the time, don’t we? And people have been referred and had to wait and wait and wait and wait and wait for months. So yes, it’s very difficult.
Interestingly, I was speaking to a consultant neurologist the other day, who moved to the UK six months ago from Ukraine, and he was asking me what do we use for preventing migraine. And so I went through the normal list of tablet preventers and Botox and CGRPs. And he said, “Oh, we use CGRPs first line, we can just go there”. And I was, “Wow, that’s amazing.” Also the cost that he quoted for me altogether in Ukraine was vastly different, much cheaper than we are hearing over here. So yeah, around the world, I think these medications are being rolled out and we can only hope that access to them in the NHS will improve over the next few years as hopefully prices come down. We can offer them, as we’ve been saying through the National Migraine Centre, but it is quite a real cost implication. Because we’re saying to patients, you know, you can try it for three months, but if it works for you, you’re going to want to stay on it. And you’re probably going to need to stay on that for at least a year, because in the meantime, we can’t guarantee if you haven’t tried three tablet preventers and you then ask to be referred to the NHS, we can’t guarantee that you’ll be seen or that you have access to the CGRP monoclonal antibodies. because we don’t have any links with the NHS. So yeah, I think my advice is to anybody who’s considering having the monoclonal antibody injections is really do your homework and find out about your local services. Find out you know how much it would cost if you came through us. All of the information is on our National Migraine Centre website, which has been newly updated and it’s very easy to find your way around and find the information that you want and of course we encourage people to refer themselves, to come and see one of our headache specialists as well. They’re in the UK and we can give them advice with obviously no obligation for them to have any of these medications if the cost is prohibitive to them.
00:43:05 Dr Rebecca Walker
But I do find that sometimes our role is doing exactly that. It is helping people navigate the system. It’s outlining what the current NICE guidance is, it’s explaining and helping people to see what the journey is to get to these medicines. We know that we work in an NHS system where financial resources are constrained and my job is often providing that guidance and support and helping with that understanding. I was going to ask you before we maybe move on to Vyapti or the gepants, have you got any top tips for self-injecting these medicines? Because occasionally I have people who come back or we get messages from the team to say “So-and-so feels like most of their injection ran down their leg. What do we do next?”
00:44:01 Dr Katy Munro
Oh yes, it’s very important to do the injection properly. When you get a delivery of the auto-injectors to your house, which is the way that we provide these medications, it’s very important to watch the videos or read the information about it, make sure that it’s kept in the fridge. We had one poor gentleman whose fridge stayed open all night and had to throw away a very expensive injection.
00:44:27 Dr Rebecca Walker
Oh no.
00:44:27 Dr Katy Munro
And travelling again is also a tricky time for some people. The injections themselves are similar to an EpiPen, which people may be familiar with, which is used for injecting adrenaline. So you basically put it onto wherever you’re going to do the injection, which is usually the thigh or the abdomen, And you press the button and because there’s a little bit of a volume that has to go in, you can’t just jab and take it away again. Otherwise you have a fountain going over throughout the room, which is not what you want. So you do need to press it and leave it in contact with your skin until you hear the clicking noise that the infection has done its work. I think people sometimes find that moving the site is helpful. It is a matter of preference I think as to where they do it. I don’t think it particularly matters. Would you agree?
00:45:24 Dr Rebecca Walker
No, I agree. I think certainly if you look at the instruction videos that come with these medicines that the tummy is fine, thigh is fine. Sometimes people use the backs of the arms. I think, though, that sounds quite difficult to do for yourself. I think the key is to, you know, just keep that — It’s not quite an in/out movement, it needs to be held in contact with the skin until the medicine’s gone in. So then I think that takes about thirty seconds. So that’s something that I’ve learned through a bit of trial and error.
00:45:55 Dr Katy Munro
When we were first prescribing them, Ajovy was only available with a pre-filled syringe and needle. And so people who are needle-phobic were a little bit concerned about that because you can actually see the needle. But I found that some of the people that had the pre-filled syringe when we then said, “oh, actually now there’s an auto-injector”, they prefer the pre-filled syringe and needle because they have a feeling of more control. But I mean, it’s very much again patient choice. Ajovy’s the only one which offers that availability. Most of the patients I prescribe newly on these treatments now will choose an auto-injection. I think that’s probably the simplest and most straightforward way to access them.
You mentioned about Vyepti. Of course this is another sort of EpiPen, eptinezumab, which is another CGRP monoclonal antibody, but it’s not one you give yourself, it’s one that’s given by infusion. And we haven’t had any experience in prescribing that yet. But I know it’s now approved in the NHS and certainly I’ve heard that Guy’s and Saint Thomas’, in the pain department there, have started during infusions of that. I also anecdotally heard of a teenager who was a boarder at a private school here in the UK, but lived in Singapore and was flying back to Singapore in the holidays to have Vyepti infusions and was doing very well on them. But I have to hasten to add she was fifteen. We will not be doing that for fifteen-year-olds. I was a bit surprised. My eyebrows went up when I heard that. Here in the UK, we do have to abide by licencing and also be guided a bit by NICE guidance. Although being independent from the NHS, we aren’t quite as constrained sometimes.
So I think Vypeti offers a good option and I think one of the reasons it’s been approved is that you know there are some people with migraine who really can’t inject themselves because they’re very needle-phobic or they may have some sort of physical or cognitive disability. That means that wouldn’t be the best option for them, or they may not have responded very well to the other monoclonal antibodies and want to try a different way. Because it’s an infusion that seems to be longer lasting, so it’s at least twelve weeks. And I’m going to be really interested to see how that works for patients as we get a bit more feedback. You know when that’s been a bit more frequently used. Have you met anybody who’s come across it or been asking about it?
00:48:48 Dr Rebecca Walker
People are asking about it because I think it’s out there in the media. I think as you say, there will be certain people who it’s the right treatment for and it’s the most convenient. I think going back to the subcutaneous injections, the under the skin injection needing to be stored in the fridge, that can be quite limiting if you travel frequently. And so as your student has experienced, having a three month or twelve weekly infusion I think could be very convenient for some people. Although you can do, I think I alluded to it earlier, you can do the three loading doses of Ajovy with three injections at a time. There is a way of doing that. It will be used in the auto-injectable medicines as well, but it’s good to have another option.
00:49:41 Dr Katy Munro
I guess the other place that it might start being used, and this is just off the top of my head really, excuse the pun, is in casualty, so if patients are going with status migrainosus, where they’ve been in a migraine attack for certainly more than 72 hours, maybe even a couple of weeks. You know if that can be offered in emergency departments, that may be something that helps. But I’m just speculating now, I don’t have any knowledge that that is where it’s going to be used. Just a thought, really. It may be helpful. We’ll have to wait and see.
I think we need to come on to the other sorts of CGRP blockers that have been available in the States for a while. And that’s the gepants. Let’s talk about the gepants. So do you want to describe them?
00:50:38 Dr Rebecca Walker
So the monoclonal antibodies that we’ve been speaking about are large molecules, they’re antibodies, they’re biological therapies. The gepants are smaller, anti-CGRP antagonists and they are tablet medicines. The one that NICE have been in consultation over most recently is rimegepant in the UK, which has the potential to be used as a rescue medicine for acute migraine, but also as a preventer, and it’s a tablet medicine that’s taken every other day if you’re using it as a preventive medicine.
00:51:16 Dr Katy Munro
Its actual official chemical name is an oral lyophilisate. I was told the other day ,and I have really struggled to say lyophili– Anyway, it basically melts on the tongue. It’s a wafer that melts on your tongue. Yeah. So you don’t have to swallow the tablet. I was pulled up on my description of it the other day, giving a talk, and so we know that rimegepant is currently undergoing NICE consultation. I was just checking because I had a feeling it was going to be announced at the end of March, but actually on the NICE website, if anybody wants to look, there’s a lot of information about the process of the consultation and it’s saying that it’s due June 2023. So we are waiting to hear whether that is going to be approved to be used in the NHS and we have no idea what the answer to that question is.
In the meantime, we are able to prescribe this for patients via the National Migraine Centre. But of course there is a fee for that because it’s a private prescription and the way that it’s working at the moment is that rimegepant is a 75mg tablet which is available in two tablet packs or eight tablet packs. And we can do an electronic prescription, which the patient then takes to whichever pharmacy they want and says “please may I have this Vydura?”, which is its trade name, and the pharmacist then decides how much that’s going to cost. So it’s a little bit of an unknown factor for our patients, which is slightly frustrating because we can’t guarantee how much that will cost. But it can be taken as one tablet in twenty-four hours for an acute attack. It can be taken on alternate days because it has quite a long half-life for prevention, but I would double check this with the company recently and if necessary it could be taken on every single day in a month. So one of the beauties of it is it doesn’t seem to be causing this medication overuse headache that we were talking about earlier on and it’s safe in people who have cardiovascular disease, which of course the triptans aren’t so useful. So a very useful additional option, but at the moment we have to say ‘if you can afford it’.
Are you finding people interested in trying it? Have you had many people asking?
00:53:59 Dr Rebecca Walker
So the people who I have seen who are asking for it are usually patients who have come from the USA and who have been either using Ubrelvy, which is ubrogepant, which is available over there or they’ve been accessing rimegepant in the US. They are often people who are on well-established anti-CGRP treatments and who use it as a very effective additional rescue treatment on top of that. And you know, I hate to be a bit of a broken record, but lots of people say it’s life-changing. And a very effective combination. Because they are smaller molecules, they are a little bit different to the monoclonal antibodies there is the potential for them — I think we do have to be conscious or cautious in patients who maybe have liver dysfunction or kidney impairment. And I think there are certain drug interactions that I also think we need to be aware of when we’re taking our histories and those might be antibiotic medicines or antifungal medicines or medicines used for HIV.
00:55:10 Dr Katy Munro
Yes, I think that’s really important. So again, we need to have the discussion with each individual person, but it’s really interesting what you were just saying. So some people are on the monoclonal antibody injections but can also use these gepant medications for acute rescue treatment. Rimegepant is licensed for acute or for prevention. Ubrelvy or ubrogepant is licensed for rescue medication. Atogepant, which is also currently going through the NICE consultation process and due to be announced whether or not we can use that in August 2023, is licensed to be a preventer. So all of them slightly different. It’s quite an exciting development I think to have these medications, we just need to get them more affordable so that people can start trying them and see if they work for them. They are in the US and I know Serena Williams has been a strong advocate for Ubrelvy and saying how it changed her life. I think she was already good at tennis but playing tennis without a migraine attack I’m sure is more helpful as well.
00:56:42 Dr Katy Munro
So there’s gepants I think. It’s really very much a question of watch this space over the next few months and years. We just really don’t know which way they’re going to go. But if anybody wants to discuss them with us, then again they can refer themselves to us at the National Migraine Centre. Interestingly, you can also take them with the triptans. So a couple of people I’ve been speaking to who’ve had that wear off of the monoclonal antibodies in that final week, they’ve had a packet of rimegepant to see if that helps in that last week, taking them alternately. Or if people are on that borderline of taking triptans on more than ten days in a month, then they may want to add in some rimegepant, don’t know if this is licensed, but these are the ways that I think people are thinking that they might just try them and see whether they can get some benefit, but we need a lot more research on them.
00:57:51 Dr Rebecca Walker
When we’re thinking about when we use medicines or use these drugs, not all of the drug essentially gets to where it needs to or sits on these proteins or sits in the receptor. So there’s always going to be a little bit of area for migraine symptoms to creep through and so yes, I think it makes sense that there is still a role for these gepant medicines on top of the anti-CGRP therapies or triptans. And as you said earlier, nothing works for everyone and something works for everyone and I think that it is great to have some choice and options on the horizon.
00:58:32 Dr Katy Munro
I just want to say a quick word about– because people may have heard of this. So I’ve been asked a couple of times about lasmitidan, and the ditans are another group of medications which are available in the US and there’s been some research, but sadly there’s no prospect of them being available in the UK at the moment. So I don’t want to say too much about those because there’s not very much to say really. But just to say, if people have heard of them and were thinking “Hmm, maybe I can try lasmitidan”, unfortunately at the moment, even through us at the National Migraine Centre, it’s not possible to prescribe that. No go.
00:59:17 Dr Rebecca Walker
Just one other thought I had, just coming back to cluster. We always talk about how, until very recently, little research that has been into the treatment of migraine, but even less so into cluster and other, they’re called TACs or TAC headaches. I think there is currently a study in Denmark underway using eptinezumab for the treatment of acute cluster as well, so then that will be out maybe in the next couple of years. So watch this space.
1:00:08 Dr Katy Munro
Yes, that would be great, wouldn’t it, for cluster patients especially episodic cluster which may you know only last a couple of months. If they have something that can be infused and last three months, but we’ll have to wait and see. We don’t know any results from that study yet. So we’ll have to wait and see. And of course again the gepants are not licensed in children at the moment and they tend to be a little bit more ahead of us for research in this in the State. So I believe that they are beginning to look at it in children but we certainly aren’t using them in children. And when I say children, I mean under-eighteens. Really, in this country, I think we would have to be cautious about that and pregnancy and breastfeeding is always a big question mark with any new medication. So currently not available for those. So we’re waiting for guidance.
So in the future, there are research studies going on to the other neuropeptides and the one I particularly found that is being researched in this great headache centre in Denmark and they’re looking at PACAP, which is a basal active peptide and maybe that going forwards we have medications which target some of the other neurochemicals rather than CGRP. And we do find that inpatients who don’t respond to CGRP blockade, maybe it’s because it’s not the most important neurochemical for them in in generating the migraine attacks. So yeah, let’s keep our fingers crossed that more research is funded and successfully finds preventative medications for the future.
01:01:37 Dr Rebecca Walker
Options. Yeah, exciting times. It’s a good time to be working in migraine medicine and I think for our patients too.
01:01:47 Dr Katy Munro
Yeah, definitely. And I always like to leave people with hope and especially if I’m talking to them about their children, they’re saying, “oh, no, I don’t want my son or daughter to go through what I’ve gone through”. And I say, “well, actually, you know, going forwards, there will be a huge number of more options available. There will be choices.” Yeah. Great. Well, I think we’ve probably covered everything we meant to cover. So thank you so much for joining me.
01:02:31 Dr Rebecca Walker
Oh, it’s been my pleasure. It’s been lovely. It’s good to talk about this topic. It’s really important.
01:02:18 Dr Katy Munro
And thank you to all of our listeners. Thank you for tuning in again and we’ll be coming along with further episodes about various topics later in this series. If you have enjoyed listening to any of our podcast episodes, we would love it if you put a review for us, wherever you hear your podcast, so Apple or Spotify or wherever you can write a review because it all helps with the algorithms. Thank you very much.

01:02:48
Next, you’ll be hearing from Josie, one of our patients, in her own words, sharing her experience of using anti-CGRP injections.

01:02:59 Josie
My migraine started when I was about thirteen with the onset of puberty. These were just very mild headaches with auras, which lasted about twenty minutes, and I was able to treat those with paracetamol. And then I had a lovely respite period during my twenties where my headaches became less frequent. But in my thirties they returned with severity and more frequent with my pregnancies and nursing periods with my children. But these most recent debilitating migraines, with or without aura, but with vomiting, started when I was in my forties. With hindsight, it was probably with the onset of the perimenopause which I wasn’t aware of at the time.
So those migraines for the last seventeen years have been chronic episodes, which I was getting on average about six times a month, so those episodes could last anywhere between three to six days plus a recovery period. So during that time I lost over a stone in weight, which I struggled to regain due to the frequency of not being well. I had to give up my job, my full-time job, and find some work that was of more flexible nature. And it’s not just impacted my life, it’s impacted the life of my friends and my family. I’ve missed out on weddings, Christmases, birthdays, holidays have been ruined, and I’ve just not been the mum and partner and friend that I’ve wanted to be because I’ve just been so unwell.
So my first anti-CGRP treatment was on 2 February 2023. The impact it’s had on my life has been life-changing since my first injection and I’ve now had four. I’ve not had one single migraine. I’ve gained ten pounds in weight, which I’ve not been able to do for a long time and I’m feeling much more energetic and confident and I’ve been able to do all the things that I used to enjoy that would trigger a migraine like exercise and getting excited about things. And it’s been wonderful and not just an impact on my life, but also my family around me. We’re doing more family things together which we can now plan confidently, knowing that I can actually make them. In the past I’ve tried lots of preventative medication for quite a long period of time, but although they work sometimes initially and in reducing the severity and the frequency of the migraines, they never stop them completely. So for seventeen years I’ve tried all sorts as well as acupuncture, taking various different supplements, changing my diet. I’ve tried hormonal treatments like the contraceptive pill and HRT, and I’ve just been living off triptans, really for the last ten years.
For anybody out there who’s a bit sceptical about trying these new treatments, I’d say give it a go. You’ve got absolutely nothing to lose. I was a little anxious to start with. I will admit I don’t like needles, I don’t like having my blood taken, but honestly, they are so easy to use. It’s a nice little cartridge. You don’t see any needle. t’s half a minute of a bit of a sting. And then it’s all over. It’s really easy to use and I had really good training from the nurse on Zoom to show me how to do it, so I’m very confident in doing it now So I’d say, give it a go, you might be a super responder like me and your life will be free of these awful miserable migraines which have such a detrimental effect on your life and those around you.

01:07:01 You’ve been listening to the Heads Up podcast. If you want more information or have any comments, e-mail us on info@nationalmigrainecentre.org.uk . Till next time.