Authored by: Julia Godfrey and Sarah Brown
Recent pharmaceutical developments in migraine treatment are exciting; CGRP monoclonal antibodies and gepants have launched in the last few years, offering effective new ways of treating attacks, but are they enough to bring relief to millions of migraine sufferers? Many are women, many suffer in silence, frustrated that they are misunderstood by the general population, their migraine excused as “just another headache”.
In this article we speak to two migraine sufferers, both of whom consider themselves to be fortunate in some respects to work within the pharmaceutical sector. Employed at Research Partnership, they are attuned to the new treatment developments that are already, or may soon be, available to them. We will also be referencing insights from two syndicated research projects into migraine conducted by Research Partnership, with both migraine sufferers and treating physicians.
Tilly first had a migraine in the summer of 2021. At that stage she was experiencing one attack for a couple of days every 6-8 months – that’s about 4 days a year. Since then, her migraine frequency has increased to roughly 16 days a month – equating to a frightening 192 days a year. Summing up her experience, Tilly says: “Migraine has a massive impact on me in all parts of my life. There isn’t a day that goes by when I do not think of migraine, whether it is because I have one coming on, am in the midst of an attack, am recovering from an attack, or am worrying that the next one might come on.”
Other sufferers like Daniela have less frequent migraines but they are just as burdensome when they happen. A common complaint from sufferers is the lack of understanding from other people and the tendency to consider this “just another headache”. Do they realise how many symptoms are associated with migraine? Headache, nausea, neck stiffness, tingling in the arms, loss of coordination of the limbs, blurred vision, brain fog and a wide range of sensitivities to light, sound, touch, smell, the list goes on.
Imagine having many of these at the same time, and you see how debilitating these attacks can be, and why it is virtually impossible to carry on with normal daily tasks, working, driving or caring for the family.
The Living With Migraine report published by Research Partnership collates data from over 300 migraine sufferers in the EU5, US and Asia. The practical and emotional burden is huge, especially for those with high frequency episodic or chronic migraine. The top ten most common symptoms are listed in Fig. 1, and on average people suffer from at least 5 symptoms.
Fig 1. Most common migraine symptoms experienced in last 3 months (Base: 316 patients in Living With Migraine 2024 survey)
“I don’t think other people are thinking of the symptoms that we actually live with. Yeah, the head pains, the nausea maybe, but it is the weird things, the sensitivity, tingling down my arms, sometimes I can’t feel the pressure on my feet, you would not think that was a migraine.”
The burden on the economy is clear, with many sufferers worried about the amount of time they take off work due to migraine, and fear of losing their jobs. The American Journal of Managed Care estimated* in 2020 that the direct cost of migraine medicine was around $11 billion a year, and the indirect cost in lost productivity was an additional $11 billion a year. About three quarters of the working Living With migraine sufferers took at least one day off work in the last 3 months due to migraine, and the average absence was 4 days. With the rise in working from home and the inevitable increase in sitting in front of a computer screen, for some, migraines have increased in frequency in the last few years since the pandemic. Daniela expects a bit of push-back when she has a migraine: “A major frustration is that it’s not understood and there’s lack of awareness, which then impacts you when you’re going through it. Sometimes people’s reaction is like, Oh yeah, did you take an ibuprofen, they just don’t understand.”
*https://www.ajmc.com/view/economic-impact-of-migraines
Misdiagnosis is common at first. Many of those affected have always suffered with headaches, and think that the new symptoms are just a part of life. At least a quarter of Living With patients reported that their migraine was misdiagnosed, mainly as a tension headache, anxiety, or sinus infection. Many also guiltily feel that they have brought the migraine on themselves through lack of self-care, not getting enough sleep, stress, the food they have eaten or dehydration.
Daniela has her own management system, when she feels the attack is imminent. She needs to get to a darkened room within 15 minutes of the pins and needles, use a hot water bottle on her feet, a cold compress on her head, and then she may or may not need to take her triptan. She realises that what works for her, may not work for someone else, migraine management and prevention is a craft: “I have read a lot of things and I think, well this may be nonsense, but I’ll try it anyway because I’m desperate”. This regimen crafting is demonstrated in the Therapy Watch data, where at least 30% of sufferers treated by neurologists, including those with chronic migraine, take OTC treatments in addition to prescribed preventives and/or acute treatments – and up to 40% take alternative therapies such as acupuncture or physical therapies.
Tilly has found it really helpful to join a migraine chat group, and share her experiences with other sufferers. The realization that she is not alone (and that there are people with even more frequent migraines) has been a source of comfort.
“I was fed up, getting them more frequently. People try to be supportive but no one really knows what it is like to live with them”. She joined a group on Facebook about 5 months ago: “I wish I had done it sooner. Having the support from people who do know what it is like is invaluable. Being on the chat group, I realize I am not crazy, other people also feel like this.”
But there has also been frustration that access to treatment varies depending on which country you live in. “A lot more people in the group in the US are on Botox or CGRPs. In the UK, we can’t even get to a neurologist. So it feels like they are getting the best chance of what is available in the US.”
Atogepant, recommended by NICE in April 2024, is the first orally available calcitonin gene-related peptide (CGRP) receptor blocker; in the US, it has been available for treatment of chronic or episodic migraine since 2023. This is offering hope to people with the most frequent, chronic migraines; Tilly is relieved she can now take it after months of waiting and “fighting” the system. “When the neurologist told me I could go on atogepant, I literally cried. I had spent over a year with very frequent migraines. Before each appointment I would feel like I was going in for battle, as I usually got so much push back and it took so long to finally get to the headache clinic.”
Daniela is speaking to me from the US on a business trip – she knows that there is a nasal spray recently available in the US for acute migraine, and if she had more frequent attacks she would be very interested in it. But, back in the UK, NICE restrictions mean that she would not be eligible for it unless she had failed on three other migraine treatments, beta blockers, anti-convulsants and anti-depressants.
Therapy Watch market share data shows that use of CGRP mAbs and gepants among neurologists is lower in the UK, and higher in Germany and Spain. We also see the efficacy of the CGRP mAbs and gepant class demonstrated in the data. Physicians state that at treatment initiation of a CGRP mAb or a gepant, 50% of patients had migraines that were significantly impacting on their quality of life; at the most recent visit, this percentage has fallen to 6%.
Fig 2. Impact of migraine on patient quality of life, based on patients on either CGRPs or gepants (DE, ES, UK)
Whilst the new class of treatments specifically designed for migraine is providing a new angle of defence for sufferers, there are a number of barriers to wide prescription. For people who suffer less frequent migraines, changing to a new medication may involve a risk of different side effects that they are not prepared to test out; also, the concept of taking a treatment as preventive is not necessarily appealing if you have irregular and unpredictable attacks.
In the Therapy Watch survey, neurologists are asked to state the barriers to prescribing preventive treatments. These focus on patient concerns about side effects (especially in Germany), long wait times (especially in UK) and other access issues such as the shortage of trained specialists to administer treatment.
Fig 3. When thinking about preventive migraine treatment in general, what are the biggest barriers to patients accessing or initiating a new treatment? Base 145 neurologists (DE, ES, UK)
“I would need to look at the side effects, for example, if it makes you drowsy then probably that’s not a type of side effect that you would want on a daily basis, if you’re a person that doesn’t haven’t very frequent migraines.”
One third of the Living With migraine patients stated that they are worried about the long-term effects of treatment on their body, and are therefore reluctant to take a regular preventive treatment, and prefer to use acute treatment only. Adherence with preventive treatment is low, with patients tending to assess their current situation, their likely stress levels and upcoming events and take prevention when they think it is necessary. It is going to take quite a shift in mindset to drive daily use of preventive therapy such as with asthma maintenance medications.
There is greater satisfaction with the patient-physician relationship in the US compared to the UK and Asia, according to The Living With survey; this reinforces the importance of successful continuity of care and knowledge of and access to the wider range of treatment options. Greater recognition of migraine as a serious condition is vital amongst the general population, and amongst some physician treaters; sufferers need to feel their disease burden is better understood. Maybe funded access to alternative therapies would help as a large proportion of sufferers value these as part of their management regime? We have come some distance with the availability of migraine-specific treatments such as CGRP mAbs and gepants, but there is still a way to go – they offer sufferers a potential new avenue for efficacy, but they do not always reduce migraine frequency substantially and carry side effects. Other new mechanisms of action are in the pipeline, as well as new routes of administration; all are hoping to bring new options for sufferers of this debilitating condition.
