A National Migraine Centre Heads Up Podcast transcript
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[00:00:00] Did you know the anti CGRP drugs are the first preventers designed specifically for migraine. Marking a significant new era for the treatment of this condition. Welcome to the Heads Up podcast brought to you by the National Migraine Centre, the only UK charity treating migraine and headache.
Dr. Jessica Briscoe [00:00:27] Hello and welcome to this recording of our podcast and it’s me, Dr. Jessica Briscoe. Hello. And we’re joined by Dr. Katy Munro virtually.
Dr. Katy Munro [00:00:39] Hello, a virtual hello to you.
Dr. Jessica Briscoe [00:00:43] A virtual hello. I mean, we can see each other, but unfortunately we’re not in the same room today. So we’re doing an episode, a long awaited episode, actually, we’ve teased this quite a few times before, but we’re doing it on the CGRP antagonist today, and it’s been an episode we’ve wanted to do for quite some time, and I know you’ve all wanted to do an episode on this too.
Dr. Katy Munro [00:01:05] It’s such a hot topic.
Dr. Jessica Briscoe [00:01:09] It is a really hot topic. And I think particularly with the UK has been campaigning to try and get this on the NHS, even though it’s been available for quite some time now privately. But we’ll talk a little bit more about that later on. So maybe if we start off with an introduction a little bit about what CGRP is and what the antagonists do, and I’ll hand over to Katy for that.
Dr. Katy Munro [00:01:32] Well, CGRP is a very short way of saying a very long name, calcitonin gene related peptide. So peptide gives a clue that this is a protein, it’s found throughout the body, not just in the nervous system and in the brain, it’s found in lots of tissues and in blood vessels. And there are slightly different types of CGRP in different parts of the body and they have different actions. But back in about, I think was, 1984 it was discovered that CGRP was a key protein in the migraine pathway in some people. And so once it was discovered that this was one of the pain neurochemicals that was implicated in migraine and particularly in chronic migraine, but also in high levels in acute migraine attacks, the researchers started looking really hard to see if there was a way of blocking or reducing CGRP and so making specific migraine treatments.
Dr. Jessica Briscoe [00:02:30] Yeah, and I think they’ve actually been searching for a way to target this for quite some time. And at the moment there are, sort of, two types of CGRP type medication. There’s the one that most people know about, which is the preventative, which is the, sort of, monoclonal antibody CGRP antagonist, the mAbs. And there’s also more of an acute- well it can be acute or preventative, type CGRP medication called the gepant. And I think we are going to largely focus on the monoclonal antibodies today. I’m going to explain a little bit more about what that means later. But we will touch on the gepants, too. But we also wanted to have a quick update about the current state of play with the monoclonal antibodies too. When we first were planning to do this episode or we decided to do this one, the monoclonal antibody Ajovy or fremanezumab- is that how you say it?
Dr. Katy Munro [00:03:26] Yeah, take a run up, you’ll get it.
Dr. Jessica Briscoe [00:03:29] Fremanezumab. When we originally said that we wanted to be this podcast, that one had just been approved by NICE for use in the NHS in the UK. Unfortunately, due to the current pandemic, the COVID pandemic, that has been put on hold for now. So the hope is that it will be available, but we just don’t know what the current status is. We’re all really excited when we thought it was going to be available on the NHS.
Dr. Katy Munro [00:04:00] Yes, that was good news. And we do know, of course, that it has been approved and in use in Scotland, as has Aimovig, but neither of those are currently available in Northern Ireland, Wales or England. So yeah, we’ll hope to have more news on that as the end of the lockdown comes and things get a little bit back to normal but just at the moment it’s only really available in England and those other countries, other than Scotland, in private clinics.
Dr. Jessica Briscoe [00:04:32] And I mean, we do have some experience about use of three of the monoclonal antibodies. Hopefully we’ll try and touch a little bit on our experience later on in the episode.
Dr. Katy Munro [00:04:44] Yes. So of course, some of our listeners are in the USA and all of these have been widely used in the USA for quite some time. They were studied in the USA, were approved by the FDA long before they were approved here in the UK. So I’m sure that people over there know a little bit more about what we’re talking about. If they’ve had chronic migraine and they may have tried one, two or even three of these. So CGRP, as we’ve said, is a protein synthesised by nerve cells. That’s the ones we’re interested in anyway. And it’s implicated in different pain pathways, including arthritis and migraine and possibly in some other headache types as well. So there’s some interest in cluster headache, isn’t there?
Dr. Jessica Briscoe [00:05:30] Absolutely, and hopefully we’ll touch on that later on as well. But we’re mainly focussing on migraine at the moment. So I think as we mentioned, they were initially- when they found out about CGRP as a substance they tried to target the treatment to look at abortive or acute treatments, sort of like an alternative triptan to try and stop migraines initially. But the ones that they came up with, first of all, I think they were not quite selective enough and they caused lots of abnormalities, particularly liver abnormalities. And there were some concerns about heart problems as well but it was really the liver abnormalities that were a big issue. And there was a lot of sort of despondency in the headache world for quite a long time about them and there was a real worry that we weren’t going to be able to use CGRP as a potential target.
Dr. Katy Munro [00:06:20] Yes, that was quite a disappointing thing for the researchers wasn’t it, I think?
Dr. Jessica Briscoe [00:06:24] Really disappointing.
Dr. Katy Munro [00:06:26] But they didn’t give up, thank goodness.
Dr. Jessica Briscoe [00:06:31] So they looked for a more targeted treatment opportunity and that’s when they came across monoclonal antibodies and maybe I’ll let you explain a little bit about that. Because monoclonal antibodies are something we talk about a lot and we thought it’d be quite nice to explain what that means.
Dr. Katy Munro [00:06:48] Absolutely. So antibodies are things that are normally made by the body as part of our immune response to things but they’ve found a way to manufacture these. By using a single parent cell, monoclonal antibodies are produced from that one single parent cell and so we can make large quantities which are suitable for using in this kind of way. So the antibodies are protein complexes and they attach to other proteins known as antigens and by binding to them, they alert our own immune systems to try and destroy that particular antigen, be that a germ or in this case a pain releasing chemical. So it is a really useful thing to have monoclonal antibody treatments and they are used in a wide range of things these days, including some cancer treatments and other things which people have found benefit by manipulating the immune response in different ways. So these migraine monoclonal antibodies are specific for migraine, and that’s the first time we’ve really had any medication that is specifically targeting migraine as such.
Dr. Jessica Briscoe [00:08:06] Very exciting. And I think the other thing, everyone sort of gets a bit nervous when they hear about immune complexes, they think, ‘oh, will that affect my immune system?’ And actually for these migraine monoclonal antibodies, it’s not necessarily the same for other monoclonal antibodies for other diseases, but these ones, these CGRP antagonists, have no effect on your immune system. So they don’t cause you to have a weaker immune system or make you more susceptible to other kind of diseases and things like that. That’s something I always like to stress.
Dr. Katy Munro [00:08:38] I mean especially in this time of pandemics, we’ve had a lot of questions, haven’t we, about, ‘oh, can I still take my monoclonal antibody injections even though there’s this horrible virus going around?’ And the answer is yes, as far as we are aware, there’s no problem with doing that.
Dr. Jessica Briscoe [00:08:57] And the other thing that’s quite nice about this is because it’s specifically targeted to migraine, it’s a neuro CGRP, as Katy mentioned in the beginning, CGRP is also important in other parts of the body, particularly the heart system and blood vessels. The monoclonal antibodies specifically target the ones for migraines. So they have not been shown to cause any problems with the heart at this time. So that’s the other worry, I think, when people talk about CGRP that, because we knew that some it caused liver toxicity or liver problems, the fact that they’ve used monoclonal antibodies makes that much less likely because it does target so much more to that brain or migraine neuronal CGRP.
Dr. Katy Munro [00:09:45] So there are actually now four monoclonal antibody treatments which have been developed, but only three of them are available in the UK at the moment. One is intravenous, so we’re going to concentrate on speaking about the ones that we’re more familiar with because of course we can prescribe these to people under a fee system at the National Migraine Centre.
Dr. Jessica Briscoe [00:10:12] We have been for about a year now.
Dr. Katy Munro [00:10:12] Yes, we have. So the three that we commonly discuss with our patients are erenumab or Aimovig, fremanezumab or Ajovy and galcanezumab/Emgality. And there is one big difference about the different ones, isn’t there, Jess? Do you want to explain about those?
Dr. Jessica Briscoe [00:10:33] Yeah. So erenumab or Aimovig target- so they essenially all have different targets. Erenumab targets the receptor which the CGRP binds to. So if you think of it a bit like being a lock and key, so the CGRP binds to the receptor and then sets off the pathway. The erenumab targets the receptor so that CGRP cannot bind there and then the migraine pathway cannot continue on and that’s how it stops migraine. Whereas fremanezumab and galcanezumab, or Ajovy and Emgality, actually target the CGRP itself so they change the shape of it all, in different ways actually, so they make it so that it cannot bind to the receptor and that’s what stops the pathway from continuing. So, you know, that’s quite important actually, because it probably has an implication on the side effects and it’s probably why some people will find one more effective than others, because it does give you that option if one hasn’t worked to try another one, which is really useful from our point of view.
Dr. Katy Munro [00:11:41] Absolutely. Yes, all three of them are working along the same pathway but as you said- I sometimes explain it thinking about a plug going into a plug socket and you know, those safety things you put on to stop children putting their fingers into it so Aimovig is the safety thing that you stick into the socket whereas Ajovy and Emgality are more like those little plastic things you get when you buy a new plug and it’s got a plastic cover on it. So I sometimes think of it that way round.
Dr. Jessica Briscoe [00:12:17] Perfect. So I mean, I think the next thing people really want to know is how are they given and how often do you have to take the medication? For those three they’re quite simple. First of all, they’re all given monthly, which is much nicer than a lot of the other preventatives that people take at the moment where they have to take them every day, except for Botox thankfully we don’t have do that every day. But it’s a monthly self injection. And actually so that’s for the first three months. You have the option with fremanezumab or Ajovy to then take it every three months instead, it’s exactly the same dose but you can take it every three months, which some people do, some people choose not to. There’s no difference in how effective it is. So usually once people have been taught how to do the injections themselves, they’re able to do at home, which means you don’t have to come into a headache centre to have it administered to you. There are some differences with the actual way they’re given though, aren’t there, Katy?
Dr. Katy Munro [00:13:22] Yeah. So there are auto injectors, a bit like the injectors that people may be more familiar with with EpiPens and things like that. So basically you put it on to your thigh or lower abdomen, and you press a button and it does everything for you. But they have also- some of them have been in a needle and syringe more traditional format. So at the moment Ajovy, I think, is just a needle and syringe, but they have made an auto injector that’s coming soon. Oh, just about the beginning dose, I think Emgality has a loading dose doesn’t it?
Dr. Jessica Briscoe [00:13:57] It does, yes.
Dr. Katy Munro [00:13:58] You have to do a double dose to start with and then it’s a single dose, but it’s again monthly. And Ajovy, if you had that three monthly one, then obviously you can space out the injections but you do at the moment have to give yourself three different injections at the same time.
Dr. Jessica Briscoe [00:14:13] Yeah. There’s no- from what I’ve heard, they’re not going to make a single injector because it’s quite a big volume.
Dr. Katy Munro [00:14:19] Quite a volume. Yeah.
Dr. Jessica Briscoe [00:14:21] So I think they would be very hard pressed, no pun intended, to get it down into 1.
Dr. Katy Munro [00:14:29] And you do, if you’re using the auto injector, I always say to people, you do have to allow time for the injection to go in because you know actually if you just click it and take it off, it will spray out into the room. So that’s not a good idea. Don’t do that.
Dr. Jessica Briscoe [00:14:43] I’ve heard of that happening.
Dr. Katy Munro [00:14:45] People do fret about how they’re going to be able to do that. And certainly before the lockdown, all of the companies had a system whereby a nurse would go and visit people and teach them how to do it. But I think now that we’ve all gone into our own homes and are not coming out, hopefully, keeping safe and protecting the NHS and other people, most of these things can be done virtually. So there are instructional videos and obviously Skype or facetime or telephone calls to teach people and even people that have pulled a face when I said, ‘it’s an injection?’ Even people who are quite needle phobic have actually managed really, really well with these, haven’t they.
Dr. Jessica Briscoe [00:15:27] Yeah, yeah, definitely. I’ve had quite a few patients that really don’t like the idea of needles and haven’t wanted to try Botox actually for that reason and have found this and have found it a bit better. There’s been lots of helpful family members who have also been able to do it. It’s not actually a difficult injection to give. So once people have learnt how to do it, it’s manageable, I think is the best way to put it.
Dr. Katy Munro [00:15:54] That’s true, yeah. And also, of course, if it works for you, people are very pleased, aren’t they? So in your experience, Jess, what would you say about how well these work?
Dr. Jessica Briscoe [00:16:05] I’ve found them really effective, actually. I think you always have that- it’s sold as a wonder drug, I think and the answer to all our migraine prayers and I wouldn’t say it’s been the answer to all our prayers, but for people that it works in it’s been astounding how much better off they’ve gotten. So I think we’ll probably move on to what the trial data said actually, because when we when we were first told about the monoclonal antibodies, they’re all pretty much as effective as each other. There’s not a huge amount of difference in the trial data, and it was very, very encouraging. So 50% of the people in the trial had a 50% reduction in the frequency and severity of their migraine. So whether or not that’s reduction in migraine days or reduction in actual level of the pain or disability, I think they mainly looked at pain, to be honest in trials, it’s very hard to measure disability. And I’d say that people who’ve responded to it have really found that that’s true. I’ve had people who’ve had their first crystal clear day in years, 5 to 10 years even. And other people have certainly found that even if they do have an attack, they can get on top of it much more easily so I think that’s probably right.
Dr. Katy Munro [00:17:26] Yes, that’s been quite impressive. And I think, you know, even if you are having pain scores of sort of eight, nine and ten every single day to improve that down to four or five is really very, very helpful for people. They begin to function and also, if it goes more quickly with the acute medications they’re trying to take, then they can reduce the number of days that they take those on and that helps if there’s an element of medication overuse headache. So it does seem to be really helpful even if people have been doing this- and there’s an episode we did back in Series 1 all about medication overuse headache, which is a really important thing to be aware of when you’re a migraine sufferer and we see it very, very commonly. But the nice thing about CGRP drugs is that you don’t have to have stopped all of your acute medication before you start them. And so by reducing the amount you need, you’re also helping reduce the medication overuse factor.
Dr. Jessica Briscoe [00:18:29] Yeah, I think that’s really important because a lot of the preventatives, apart from Botox, actually, they just won’t work as well as we’ve mentioned before, but the monoclonal antibody seem to be just as effective whether or not medication overuse is there. So I think that’s a really important point, actually, definitely worth bearing in mind when thinking about which preventative people want to try.
Dr. Katy Munro [00:18:52] There is a certain group, of course, that don’t really find that things are getting any better for them and they I’ve called ‘the disappointed group’. You know, there’s ‘the amazed and astounded group’ that have had their lives transformed. Then there’s ‘the pleasantly surprised group’ who have got a 50% improvement. And then there’s ‘the really disappointed group’ who have just put all their hopes and, in the UK certainly, put all their money into buying three months supply and they come back and say it’s no different. So what do you say to those?
Dr. Jessica Briscoe [00:19:29] I find it heartbreaking. So I mean, I find it very difficult- much more difficult probably in the UK than clinicians may find it elsewhere, just because we’re less used to people paying for the medications anyway. But I always advise people that the amount of time that it takes to be effective is variable. So it can be as little as two weeks, but it can be as much as six months. And that I think was particularly- that was something we picked up when we went to that big meeting last year when we had all of the headache specialists from around the world, particularly in the US and Australia, talking about their experiences where they’d been prescribing it for four years or so since it first came out. And it looks like it can take at least six months in some people to really get working. It does seem to have a cumulative effect. Now that can be really difficult if you’ve taken it for three months, you’ve spent quite a lot of money on it for that amount of time and you’re finding that there’s no improvement at all. What do you do? Do you keep going for another three months? Where, actually, it may not be helpful or you might find a bit of improvement. So I try and advise people that it can take that long. And if they’re willing to carry on for six months, some people have noticed a difference at that point. The other option is whether or not they switch to a different monoclonal antibody, because some people who don’t respond to one will respond to another one. That’s the advice I tend to give.
Dr. Katy Munro [00:20:55] That’s certainly been the case. When we were initially prescribing Aimovig, of course, we were prescribing a 70 milligrams starting dose but I think both you and I and our colleagues have now started just going straight to 140mg. Although I have had some patients on the 70mg who did really, really well, but there’s no price difference so there was no point really in carrying on with- quite often we were having to double up the dose, weren’t we?
Dr. Jessica Briscoe [00:21:22] At the beginning don’t forget, it was two injections before they had the single injection device. So that certainly made a difference as well.
Dr. Katy Munro [00:21:28] Yes, that’s true.
Dr. Jessica Briscoe [00:21:31] So people were having to give twice the injections. I think that also played into why we were giving the single dose first of all. But it does seem to be- actually if you look at the licencing, they have suggested 70 milligrams for episodic migraine and 140 milligrams for chronic. So, you know, I mean, I usually prescribe it in high frequency episodic migraine, which we discuss in another episode.
Dr. Katy Munro [00:22:00] It is possible to take it if you have just episodic but then it becomes a judgement call really doesn’t it, as to when is it worth having something. If you’re only getting one migraine a month, it’s a very expensive way of getting rid of your migraines, whereas if you getting high frequency migraine then I think a lot of people feel that it’s worth it. Now of course on the NHS, it is not going to be licenced for high frequency, it’s only going to be licenced for chronic migraine. Hopefully when we finally get the final guidance it will be more clear. But I think as far as I’m aware, it’s going to be for people who have tried and failed three preventers. They didn’t specify Botox- I’m talking about Ajovy at the moment.
Dr. Jessica Briscoe [00:22:44] And in the UK and Northern Ireland and Wales. It’s slightly different in Scotland again because they’ve got a different body and it’s actually licenced for frequent episodic there.
Dr. Katy Munro [00:22:57] Yes, it is. Yes. But then of course, it’s local discretion up there, as well. It’s a bit of a minefield, isn’t it, really? And I’m very aware for our chronic migraine sufferers and also for the high frequency ones, you know, to have to wait till the end of lockdown to get a chance to have this. To then have to be referred through the NHS, through a, probably, a general neurology department via then to a headache specialist department and all the delays and hold ups that they have, I feel really sorry for people who have to wait so long for this.
Dr. Jessica Briscoe [00:23:35] It’s awful. And also, don’t forget, people who are having- I mean, there are still a very few injectable clinics happening. I was reading about one today that they’re still doing one in Glasgow, I believe, but it’s very much area dependant.
Dr. Katy Munro [00:23:49] I think that’s just about to finish.
Dr. Jessica Briscoe [00:23:52] Exactly. So I mean, there are one or two injectable clinics going on, but people who have been relying on Botox or nerve blocks, because some people still use regular nerve blocks for their migraine. And we’re obviously not doing any injections either. You know, it’s heartbreaking to not even have this as an option, at the moment. This would be what a lot of people would move on to. Anyway, we’ve digressed but I wanted to talk about who it’s safe for. Who is it safe for?
Dr. Katy Munro [00:24:21] Yes. So it’s generally very safe, which is really very nice to be able to say. But of course, we don’t do studies on these kind of new drugs in people under 18, there is also very limited study data in people over 65, although one of the drugs has started to look at some over 65s and that’s the Emgality. There’s no data for pregnancy of course, we don’t use these in pregnant women. And the current advice is to stop and let the medication wash out of your system for about six months before trying to conceive so that’s really important. That’s mainly because we just don’t know. It isn’t because we know it’s dangerous. It’s because we don’t know if it’s dangerous and that’s the thing to emphasise about any of these new drugs is that the more that they’re used, the longer that time goes on with us gathering data, then the more information we’ll have about safety and side effects and things like that.
Dr. Jessica Briscoe [00:25:28] With the pregnancy, it’s a bit like we discussed in our Botox episode, isn’t it? Hopefully more data will come over time. But as we can see from Botox, it takes a long time for that safety data to come through.
Dr. Katy Munro [00:25:39] Yeah.
Dr. Jessica Briscoe [00:25:40] You were about to talk about heart.
Dr. Katy Munro [00:25:42] Yes. I was going to say about cardiac things.
Dr. Jessica Briscoe [00:25:45] I think it’s important. So, as we’ve mentioned, CGRP is something that is around in heart muscle and also the blood vessel system as well. And we always check blood pressure and a lot of other clinics, when they were doing the trials, seem to do that too, just because we don’t know whether there is an effect on people’s blood pressure when taking the monoclonal antibodies. Now, on the trial, there was no evidence of any safety problems, nothing’s been officially put out there yet. But it is something that we are looking out for because we’ve had one or two anecdotal pieces of information about blood pressure. But as Katy’s always telling me, anecdotal stories don’t constitute-
Dr. Katy Munro [00:26:35] It’s not evidence.
Dr. Jessica Briscoe [00:26:36] You put it better than me.
Dr. Katy Munro [00:26:39] The plural of anecdote is not evidence.
Dr. Jessica Briscoe [00:26:42] Thank you. That’s a memory I love that phrase. And then I think the other thing to talk about, which we’ve touched on, is the cost. The cost is the other real, I’d say, contraindication to the CGRP cbecause it is very expensive.
Dr. Katy Munro [00:26:58] Especially as a lot of our chronic migraine patients have had a real financial hit as a result of their migraines. They may well have had to give up their job or go part time or you know, a lot of them are really struggling. So, you know, we as a charity, of course, can’t afford to give it out free, sadly. And so we do have to charge for it just by the nature of things. But, you know, if people are paying for it, even if they are still, you know, reasonably comfortably off, they still find it pretty heavy because it’s working out anything between £300 or £400 a month, isn’t it? At the moment. It seems to vary as prices get tweaked by the companies, so always double check the price before you- this is not official. Things may change.
Dr. Jessica Briscoe [00:27:52] I have to double check the price every day. I think the next thing to talk about is side effects. That’s the thing that everyone with migraine medications, particularly preventative medications, is always very keen to talk about. I’m often saying to people, people with migraines tend to seem to be much more sensitive to medication side effects, but this is actually one of the ones where we have some good news, actually, because there aren’t many significant side effects with CGRP that we’ve discovered so far. As I’m always saying, it’s a new medication, things change. But the main things that I’ve seen are injection site reactions. So particularly muscle spasms, some rashes around the injection site. Pain. I think some people get indentations, but I’ve not seen huge amounts of that. That usually improves when people get better at self injecting, when people have practised it more and rotating sites and also finding out where works best for them. So some people find injecting into the abdomen better than the legs and things like that. And then I’ve seen a couple of episodes of generalised itching, but the big one that everyone worries about is constipation.
Dr. Katy Munro [00:29:06] Yeah, constipation is quite a common one I think. Normally people say, ‘oh, I’d rather have constipation than migraines’, so that’s fair enough. And also there are some quite easy remedies for constipation. The one I normally recommend first is just dosing yourself up with magnesium citrate because it’s a nice medication for preventing migraine anyway, a supplement that you can buy easily over the counter and it is quite laxative. So yeah, two birds with one stone.
Dr. Jessica Briscoe [00:29:34] That’s usually the downside to it.
Dr. Katy Munro [00:29:37] Yes.
Dr. Jessica Briscoe [00:29:37] Yes, I agree. I often say that. And other simple things like increasing your water intake, flaxseed works quite well, but usually I advise the more natural things. But I have actually had one or two that have had a really significant constipation, but they have been people that have been prone, they have had a slightly sluggish gut in the first place. And then the other thing- I think you’ve seen it- I’ve certainly seen it, but insomnia. I’ve particularly seen it with higher doses of the erenumab/Aimovig, but it has been reported as a side effect as well and seems to resolve if people go down to the lower dose or change to a different one. I’ve not seen it so much with the other ones, but it’s definitely has been reported.
Dr. Katy Munro [00:30:19] I haven’t seen much of that, I have to say.
Dr. Jessica Briscoe [00:30:21] Oh, I thought you had.
Dr. Katy Munro [00:30:23] I have had a couple of people who’ve had kind of flu symptoms for day or two after the injection and then that’s gone off. And I think also initially reported were lots of upper respiratory tract infections.
Dr. Jessica Briscoe [00:30:38] Yeah, and UTI infections.
Dr. Katy Munro [00:30:40] Yeah. But whether that is just because that’s quite a common thing to get anyway, I don’t know that there is any real logic behind that, but none of them are significant or serious side effects are they? Just minor really.
Dr. Jessica Briscoe [00:30:55] I haven’t seen any particular increase in upper respiratory tract infections. It’s something I get asked a lot over winter, I’ve noticed, but actually it does seem to be the normal winter bug. But it’s certainly not a significant trend that I’ve seen at all. And then the other thing- we’ve touched on it, blood pressure. As we said, we check blood pressure in our patients and get people to check it themselves at home. I haven’t seen anyone have an increase.
Dr. Katy Munro [00:31:20] I haven’t, no. I haven’t come across that as a problem at all in anybody.
Dr. Jessica Briscoe [00:31:25] No, I tdare say it seems quite safe, but it is early days and if anyone is on it and does find that they have side effects, it’s really important to mention these to your doctor so that it can be reported because the only way we learn about these is to report them.
Dr. Katy Munro [00:31:44] Yes. And I have a couple of patients who have reported things which I am not even 100% sure whether they are anything to do with the medication, and I have filled out yellow card reports and sent them off because that’s the way that doctors report significant side effects from new drugs. And the companies are very, very keen to hear if there is anything that is untoward that’s happening, even if you’re not 100% sure, just let your prescriber know about it.
Dr. Jessica Briscoe [00:32:12] So you were about to ask, before I rudely interrupted, how long people should stay on them for? And again, we’ve alluded to this a little bit. So the more time- we’re going on the basis of the data from other countries, because Australia and the US have had it for a lot longer than we have and we’re going from what they said. But the current advice is to try it for at least six months because it can take that long to start working and then staying on it for at least one year. At that point people can try coming off it because you know fairly quickly whether or not- it comes out your system fairly quickly. Well, they say six weeks. It’s got a half-life of about six weeks, I think. I don’t really want to be quoted on that, it could be a bit shorter than that. But you usually know fairly quickly. But there is a question- it doesn’t seem to be like the other preventative where we’ll say stay on them for between six months and a year and then try and come off them because your threshold will stay up. That doesn’t seem to happen so much with the CGRP drugs. I don’t know if you feel the same way, Katy?
Dr. Katy Munro [00:33:21] Well, I normally say to people, it depends, especially the way that we’re prescribing them where people are having to pay. I tend to be saying, well, it’s partly a cost discussion that we’re having, if you want to keep paying for it after a year or even after six months, because if you know that you’ve dramatically improved- normally on a preventor, we would say, well, if your migraine has settled down, your brain has settled down, the irritability is much better, then you can wean yourself down, but you can’t really wean yourself down off these. You have to just stop taking it and see what happens. But at least if you stop them and things reccur, then you have got the option to go back on them again knowing that they work. The only thing I would say about a couple of patients who’ve I’ve had this discussion at around a year and they are so happy and their lives have been so transformed that there is no way that they want to come off them ever. But I think we will keep having the conversation again as knowledge and confidence grows.
Dr. Jessica Briscoe [00:34:25] I was going to a completely agree with you. The people that I’ve had- I suppose because of the amount of time that we’ve been prescribing it for, the number of people that have stayed on it for the year are so happy with it that they’ve, sort of, more been asking, do I have to come off it? And we say, No, not at all, if you would like to carry on, please do.
Dr. Katy Munro [00:34:44] I think, there’s been, in the studies, they’ve had people who’ve been on it for four or five years now that they’re following. So as far as I’m aware, there’s no evidence that that’s a dangerous thing to do, or that there’s any problem of tolerance building up.
Dr. Jessica Briscoe [00:34:59] Yeah. So that was the other thing I was going to mention. Everyone gets worried, for obvious reasons, about whether they’ll become tolerant or it might be less effective over time and that doesn’t seem to be the case. I mean, the other thing I always like to point out to patients is that your normal migraine activity still goes on underneath. So you may find that some months are worse than others, but that will be to do with what is going on in your life. Don’t take that as a sign that you’re becoming tolerant to it or that it’s not working.
Dr. Katy Munro [00:35:33] Yes.
Dr. Jessica Briscoe [00:35:33] Just think about how much worse it probably would have been before you were on the monoclonal antibodies.
Dr. Katy Munro [00:35:40] I think that’s true. Yeah, I had somebody the other day and he said, ‘well, I was really not so good in that second month, but then I was travelling for work, really, really stressed, didn’t have a good night’s sleep’. And you think, well, yeah, I mean, you know, it’s not going to solve- it’s not a miracle cure. But, it’ll help. It will help.
Dr. Jessica Briscoe [00:35:57] Absolutely. And then I think, again, you’ve touched on this. Can you switch between different types of monoclonal antibody? Is that safe to do?
Dr. Katy Munro [00:36:07] Well, we used to think that you had to have a bit of a gap. But I understand now that the guidance is, if you’re switching because one hasn’t worked, you can switch straight over to another one and try that. If you’re switching because one has given you side effects, then it is wise to let it have a washout period of anything between three and six months. So that you’re completely clear, there’s no cause for confusion if you then start another one, and then you can give that a decent trial to see if that one will help. Because of course we do find that with triptans and with other preventatives, just because one doesn’t work doesn’t mean that another one won’t as well. So I think it’s a trial and error thing again with the three different ones. And I certainly have patients who’ve come over from the States who’ve tried all three, one after the other, and there doesn’t seem to be any problem in doing that.
Dr. Jessica Briscoe [00:37:04] Yeah. And actually in the early days when we didn’t know- as you said the advice was to wait three months for a while. But back when Ajovy first came out, I was happily switching one or two people before I knew that advice and nothing untoward happened.
Dr. Katy Munro [00:37:19] People have been fine.
Dr. Jessica Briscoe [00:37:22] Very pleased that that advice has changed. Probably we should talk about cluster headache because we’ve done a cluster headache episode and we do have quite a few patients who have cluster headache and, generally the options for cluster headache treatment are even worse than for migraines. So there was a lot of excitement actually as well when CGRP came out and its implications in the treatment for cluster headache. Are they usable or is there any specific one that’s suitable for cluster headache?
Dr. Katy Munro [00:37:52] Well, I think it was Emgality who have actually done some studies on cluster headache, but the evidence is slim at the moment and I think the European licencing body has not approved Emgality for use in cluster headache. So I think sadly and it would be wonderful if they were all super effective in cluster because we desperately need something like that for our cluster patients. But I think at the moment the jury’s out really, isn’t it?
Dr. Jessica Briscoe [00:38:25] Yeah. But hopefully we’ll sort of- we keep our fingers crossed about that because it would be lovely if one- a little plea to the drug companies if someone could do a trial on cluster headache. That would be wonderful, because it is something that I think the cluster headache community are desperately in need of. Some evidence and new treatments that are targeted to that type of headache.
Dr. Katy Munro [00:38:50] So now we’re just going to have a brief section where we discuss the other kind of CGRP medications which are not available in the UK but are available in the US, and that’s the gepants. And these are used as abortive or acute medications and they’re likely to be marketed over in the UK and are already being used in the States as an alternative for triptans, which we have done a very popular episode on in series one. But, of course, the problem with the triptans has been that they are not safe for people with cardiac disease, angina or anything like that. So we do have to be quite careful with them. So do you want to say a bit more about the gepants, Jess?
Dr. Jessica Briscoe [00:39:36] Yes. They are another type of antagonist or a blocker to the CGRP receptors, but they’re much smaller molecules. So unlike the monoclonal antibodies, they do go across- they cross over into the brain, which has been a problem for side effects in the past. They also seem to affect- they don’t just affect the CGRP system, but they seem to also affect another really important system, and again, I think we’ve discussed in a previous episode, called The Trigeminal System, which is really important in lots of headache disorders, particularly the TACs actually, the cluster headache group of people. But also migraine too. The important thing about gepants is that they do not cause vasoconstriction or tightening of the blood vessels, which is the real problem with people who have high blood pressure, heart problems like angina or a history of strokes because if you have any of those problems, you don’t want to close up those bloody vessels anymore.
Dr. Katy Munro [00:40:43] Definitely not.
Dr. Jessica Briscoe [00:40:43] No, definitely not. So that’s why it’s been really important for us to try and find an acute alternative which is targeted to migraine like triptans are- or headache like triptans are. And the good thing about gepants is that when they looked in trials, they were as effective as triptans because actually triptans are a very effective medication. Again, there are seven different triptans. There are also different types of gepants. I think there are five at the moment that have been have- there are two available in America but there are five that have been developed.
Dr. Katy Munro [00:41:24] Yeah.
Dr. Jessica Briscoe [00:41:25] So the first generation of gepant were those ones that caused problems with the liver and because in the trials they caused those problems that really caused a big pause in looking at the gepant. But I think once the sort of monoclonal antibody train got started, people started realising that you could affect the CGRP system more safely and the, so called, second generation gepants were developed, which have been tested and have not had any liver abnormalities and more importantly, have been tested in people who are known to have heart problems and haven’t caused any worsening of the heart problems or made them more at risk of having strokes. That’s really exciting.
Dr. Katy Munro [00:42:12] That is really good news. And I had a patient the other day who’s allergic to triptans, really quite severely allergic, ended up in hospital after taking one, which I have to say is very, very unusual. And so he can’t take any of the triptans but would possibly be able to take the gepants and might be the answer for him. So we’re excited to know whether we will be able to get these. Of course, with any new medication, they’re always expensive. And so we will have to go through the NICE guidance and procedures as to whether or not, even if it’s licenced, whether it’s available easily through the NHS, and there’s no sign at the moment of that being any time soon, so don’t hold your breath. So the ones that we’re talking about that are already FDA approved in the United States are Nurtec or rimegepant, and Ubrelvy/ubrogepant. They like to cause these really tricky names just to keep us keeping our teeth in.
Dr. Jessica Briscoe [00:43:15] Tripped right off the tongue. I thought I’d let you say them.
Dr. Katy Munro [00:43:19] I love a challenge. So yeah, that’s probably about it for CGRPs at the moment. A very exciting area of development. So when people come and they’re feeling very down and they say, ‘Oh, I’ve tried everything’. I’m always happy to say, ‘Look, even if you feel as if you’ve tried everything, you probably haven’t and there’s lots of hope for the future because there’s so much research into these exciting new medications’, probably not enough research because we think migraine should be a lot higher up the agenda.
Dr. Jessica Briscoe [00:43:54] And also the other thing, I think really important to highlight, I think our discussion about cluster headache made me think you know, migraine doesn’t get enough research, these rarer forms of headache get infinitesimally less research. So I really think there should just be more headache research in general.
Dr. Katy Munro [00:44:12] Definitely. And you know, it is devastating when you have any kind of severe recurrent headache pain and we really hear that on a very frequent basis.
Swati [00:44:25] That was Dr. Jessica Briscoe and Dr. Katy Munro sharing with you the various antiCGRP medications we have available in the UK. In the next section we are sharing with you the experiences of two patients who’ve tried and are currently using Aimovig and Ajovy for treating their migraines. Hi, Ken. Thank you for joining us on our podcast today. We understand that you are currently using Ajovy, antiCGRP injections for treating your migraines. How has the experience been so far? When did you start it?
Ken [00:45:09] I started it in December or end of November, and initially it was fantastic. December, January, three attacks in both of those months. And it was like, you know, my life had changed. This was the wonder drug. But it has started to tail off. It’s still good but for February, March I had seven attacks in those two months, seven in each month. And then this month hasn’t been brilliant and I’m up to eight so far this month. So it’s tailed off a bit, but it’s still better than not doing anything, if you know what I mean.
Swati [00:45:54] Before using the antiCGRP injections or before using Ajovy, how many headache days or how many migraine days would you have in a month?
Ken [00:46:02] Well, like I say, I went straight from Aimovig to this one. So again, that one started quite well and then by the end I was up to 15 a month and that’s sort of where I was at before I started taking the Aimovig as well. So yeah, sort of, 15-16 a month and then since like say the first couple of months on Ajovy was fantastic, it was only three. February, March seven. So, kind of, where I’m at at the moment it’s probably about half the attacks that I would get if I wasn’t taking it at all.
Swati [00:46:43] Okay. And how about the severity of attacks?
Ken [00:46:49] Pretty bad. The severity isn’t any better, shall we say, which I was expecting it would. I say that they are not all, you know, 10/10s, if you like.
Swati [00:47:00] Okay.
Ken [00:47:01] They’re, sort of- over February-March let’s say, I had two 10/10s and the rest are sort of around about a 7/10 or 6-7/10 mark. So I can still function on those ones. But when it gets up to 9s and 10s, that’s when it knocks me out. So I am still getting them but not as frequent.
Swati [00:47:26] Okay. At least it’s improved on the frequency of it, if not the severity, but which is often what we look for.
Ken [00:47:31] Yeah. More so on the frequency. Yeah. Exactly.
Swati [00:47:36] Is it something you would recommend for people to try?
Ken [00:47:40] I would recommend people giving it a go. Yeah. I mean, you know, if you’re sort of where I was at with, you know, over half the month, if you like, in pain. I’d try anything. But like I say, I will continue this for the next few months, but it’ll be interesting to see whether the severity or the frequency, should I say, starts getting more and more worse. But yes, I would recommend it definitely. I would recommend people trying it.
Swati [00:48:08] Well, great. Thank you so much for sharing your experience with us, Ken. Thank you.
Ken [00:48:12] That’s alright. No problem at all.
Swati [00:48:16] Thank you, Joanne, for joining us today on our podcast. Just to understand, Joanne is currently taking Aimovig for her migraines, and I’m going to ask her some questions about the CGRP treatments and how she feels about that. To start off with, Joanne, could you just tell us a bit about your migraine journey. So when did you start getting migraines?
Joanne [00:48:36] I started getting migraines about ten years ago. They started quite sporadically. I wasn’t really affected terribly by them and then they just got worse and worse to the point that I had to give up my job and various things that I was doing like counselling, teaching children and I did a little bit of acting and it all had to go by the by because I was held up in a room for so many days and months being so ill.
Swati [00:49:08] Horrible.
Joanne [00:49:08] So yeah, it wasn’t good. It was pretty awful. They started really in full flow around about 2010.
Swati [00:49:17] And what kind of treatments or medications were you trying at that point of time?
Joanne [00:49:21] Oh, goodness me. Started on one of the triptans. I can’t remember the name of it now, but the second triptan was maxalt. But I kind of- my body, I don’t think, liked them. It did wipe out the migraine, but often it would come back. And I think it just escalated the occurrence of the migraines. Then I was on a migraine drug but I can’t remember the name of it.
Swati [00:49:51] That’s fine.
Joanne [00:49:51] And then I tried-.
Swati [00:49:54] So you tried a couple of preventatives.
Joanne [00:49:55] Yeah. And I can’t remember the names of them now. My mind’s gone blank.
Swati [00:49:58] There are so many of them, I can absolutely imagine. So you’ve tried Aimovig? When did you start your- when did you have the first injection?
Joanne [00:50:08] So I had my first injection on the 8th of February.
Swati [00:50:13] Was it painful?
Joanne [00:50:16] Not really. No. I’m okay with needles.
Swati [00:50:22] It’s like an auto injector pen?
Joanne [00:50:23] Yeah.
Swati [00:50:24] Slightly better than needles. So did you immediately sort of feel a bit of effect or…?
Joanne [00:50:33] I would say yes. It’s transformed my life because whereas before I couldn’t make plans, holidays were cancelled, various occasions with friends were cancelled. I always had to pre-empt my invitations with ‘if I’m okay’. Theatre trips that were booked months ahead or weeks ahead had have a backup plan for everything. Even the job that I do, which is looking after dogs now because it’s something that I can do flexibly because of my migraines. I always had to say to my clients, ‘oh, have you got a back up plan? Is there someone else that can take your dog for a walk?’ But now, since I’ve been on Aimovig, even my friends have noticed that I don’t say ‘if I’m okay, I’ll be there’. And I’ve kind of taken it for granted now that I will be okay. Having said that, I still get the occasional migraine, but it’s very mild.
Swati [00:51:37] So if you compare it, so before taking Aimovig, how many headache or migraine days did you have? From the top of your head, how many would you have in a month?
Joanne [00:51:46] I would probably have 10 to 12 headache days. But I would say 3 to 4 days twice a month I would be held up in a room in the most dreadful pain. On a scale of 1 to 10, it would probably be hovering between a 7 and an 8 for about 72 hours it would be. And it was just awful.
Swati [00:52:12] And that’s reduced considerably within the Aimovig?
Joanne [00:52:16] Oh my goodness. My migraine days are very few and far between now. I might get 2 or 3 a month, but they are a 2 or 3 in terms of severity so I can manage them.
Swati [00:52:29] Exactly. So that’s just completely- both in terms of frequency and severity, that’s just gone down completely.
Joanne [00:52:35] Yeah. It’s been a miracle drug for me. It might not work for everybody, but it certainly did for me.
Swati [00:52:41] I am glad that this CGRP drug is working for you. And thank you so much for joining us on our podcast.
Joanne [00:52:48] That’s ok. Thank you.
[00:52:53] You’ve been listening to the Heads Up podcast. If you want more information or have any comments, email us on info@NationalMigraineCentre.org.uk. Till next time.
This transcript is based on a past episode of the Heads Up podcast and reflects information available at the time of broadcast – some facts may have changed or new treatments become available since.
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