NICE rejects rimegepant for acute migraine treatment

27th February 2023

Rimegepant has been rejected by the UK’s NICE for the acute treatment of migraine either with or without aura as well as for episodic attacks

In an appraisal consultation document from NICE, rimegepant is not being recommended within its marketing authorisation, for the acute treatment of migraine with or without aura in adults, or for the prevention of episodic migraine in adults, who experience at least 4 attacks per month.

Rimegepant belongs to a class of drugs referred to as ‘gepants’ which are calcitonin gene-related peptide receptor antagonists. Calcitonin gene-related peptide has been associated with sensitisation and pain generation but also plays a role in vasodilatation. In a recent phase 2/3 trial, oral rimegepant, when taken every other day, was found to be effective as a preventive treatment of migraine, with its tolerability similar to placebo.

It is proposed by the manufacturer that rimegepant is used for acute migraine treatment in patients who have failed to respond to two or more triptans. However, in its consultation document, while accepting that the drug is likely to reduce pain at 2 hours post-dose more than placebo, NICE added that the evidence submitted by the manufacturer, for patients who have not responded to two triptans, is uncertain and hence requires more evidence. Moreover, while it also reduces monthly migraine days, NICE argued that there is an absence of comparative long-term evidence to support this view. As a result, the organisation believes that this clinical uncertainty affects the certainty of the cost-effectiveness estimate and which is likely to be above what NICE considers to be an acceptable use of NHS resources.

In response to the consultation, the Migraine trust has expressed concern, stating that ‘a significant proportion of those seeking help from The Migraine Trust have an inadequate response, or contraindication to the best current acute treatment triptans, or have medication overuse headache as a result of inadequate care and treatment of their migraine.’ The statement added that ‘we believe that Rimegepant is an important opportunity to help those who have medication overuse headache and prevent others from developing it.’ These concern arose following a 2019 survey of 1,800 migraine sufferers undertaken by the trust, which found that migraine treatments caused medication overuse headache in a third of respondents.

Chief executive of the migraine trust, Rob Music said that ‘we are very disappointed by this decision and urge those affected by migraine, and particularly those without an effective treatment for migraine and who have experienced medication overuse headache, to respond to NICE’s consultation and let it know how much this new treatment option [rimegepant] is needed.’

Enlarged perivascular spaces revealed by MRI in migraine sufferers

19th December 2022

The presence of enlarged perivascular spaces in the brains of migraine patients may indicate the presence of glymphatic disruption

The identification of enlarged perivascular spaces in the centrum semiovale in patients with migraine compared to healthy controls, is suggestive of a disruption in the glymphatic system according to the findings of a study using ultra-high-field 7T MRI and presented at the Radiological Society of North America conference 2022.

Migraine is a common headache-related condition that affects an estimated 12% of the population. With the development of magnetic resonance imaging, it has become clear that some migraine patients (both with and without aura) are at an increased risk for subclinical lesions in certain brain areas. Such lesions include white matter hyper-intensities (WMH), i.e., lesions that have infarction features but which do not cause any clinical symptoms or other stroke-related signs. In addition, cerebral micro-bleeds (CMBs) are another biomarker of small-vessel disease and which have been found to co-occur with infarcts more often in migraine than in control patients. Advances in imaging techniques by 7 Tesla MRI might improve the visualisation of smaller anatomical structures and allow detailed pathological findings with a high spatial resolution by reducing the voxel size related to the increased signal-to-noise (SNR) ratio.

In the present study, US researchers used the 7T MRI modality to study microvascular changes in the brain due to migraine, particularly in perivascular spaces and compared the findings with those seen in headache-free control patients. They enrolled participants with both chronic migraine (CM), episodic migraine without aura (EMWoA) and age matched healthy controls. Patients were excluded if they had overt cognitive impairment, a brain tumour, prior intracranial surgery, contraindications to MRI or if they suffered with claustrophobia. The team calculated enlarged perivascular volume spaces (EPVS) in the centrum semiovale (CSO) and basal ganglia (BG), WMH using the Fazekas scale, and CMB using the micro-bleed anatomical rating scale. In addition, they also collected clinical data such as disease duration and severity, symptoms at time of scan, presence of aura, and side of headache.

Enlarged perivascular spaces in migraine and control patients

A total of 10 CM, 10 EMWoA and 5 health control participants were included.

The results showed that the number of EPVS in the CSO, but not in the BG, was significantly higher with migraine compared to healthy controls (p = 0.04). However, while the frequency of WMH and CMB in migraine did not significantly differ from controls, among migraine patients, there was a significant correlation between EPVS quantity in CSO and deep WMH severity (p = 0.04).

The authors concluded that there were significant differences in the EPVS in migraine compared to controls and which might indicate be suggestive of glymphatic disruption, i.e., the system for clearance of waste materials from the central nervous system and which utilises perivascular channels. Nevertheless, whether such changes affect migraine development or result from migraine is unknown.

In a related press release, study co-author Wilson Xu, from Keck School of Medicine of the University of Southern California in Los Angeles, said ‘although we didn’t find any significant changes in the severity of white matter lesions in patients with and without migraine, these white matter lesions were significantly linked to the presence of enlarged perivascular spaces. He added how ‘this suggests that changes in perivascular spaces could lead to future development of more white matter lesions.’

Citation
Xu W et al. Migraine-Associated Vascular Changes on Structural 7T-MRI. RSNA 2022