Migraine treatment - Is it time for a new pair of (GE)PANTS?

Migraine is a miserable and debilitating condition and we’re all aware of the impact it has on our patients, friends, family and work colleagues. The latest 2019 Global Burden of Disease Study found that migraine was one of the most common causes of disability in people aged under 50, and in women under 50 it was the top cause of disability. It is therefore somewhat surprising that we’ve barely had any advances in migraine treatment since triptans came on the market 30 odd years ago. Apart from some evidence on the use of candesartan as a preventative treatment, we’ve essentially been trying the same acute and prophylactic treatments with limited and variable success since the 1990s.

However, as is often the case, having not seen a new treatment for decades, we now have a flurry of new drugs, all of which target the calcitonin gene-related peptide (CGRP). Over the past few years injectable monoclonal antibodies (MABs) targeting CGRP or it’s receptor (e.g. erenumab) have been developed, with a number now recommended by both NICE and SIGN for use as preventative treatments, if standard medications have been ineffective. But there are a number of barriers to accessing these drugs - they have to be specialist initiated, waits to see said specialists are often years not months, and they are eye-wateringly expensive. All in all, for most of our patients this feels like a ‘nice if you can get it’ situation - a drug that is accessible to small numbers only. 

Will this change with the new kid on the block rimegepant - a ‘gepant’ which has just been given the green light for acute migraine treatment by NICE in draft guidance, which was announced in a blaze of publicity in both national and medical press over the past couple of weeks. So what are the gepants? Will they really be a ‘step change’ in management, as NICE have confidently announced? And will they live up to the hype and genuinely ‘bring new hope’ to migraine sufferers who have not responded to current treatment options? 

The gepants are small molecule CGRP receptor antagonists. Rimegepant was the first in the class to be recommended as an option for preventing migraines by NICE in July 2023, with a further gepant, atogepant, currently being reviewed by NICE, also for migraine prevention. This latest (draft) guidance is the first to recommend use of a CGRP drug for acute migraine treatment, recommending rimegepant in people who have not responded to ≥2 triptans, or in people whom triptans are contraindicated/intolerant and do not respond to paracetamol or NSAIDS. Final guidance is expected to be published later this month, but given the publicity surrounding it, changes are unlikely.

The draft NICE guidance was wooly on the details of the evidence (to say the least, and that is a whole discussion in its own right…), but a Cochrane review showed that vs placebo there were almost double the numbers pain free at 2 hours with rimegepant and about a 50% increase in those free from the ’most bothersome symptoms’ at 2 hours with rimegepant. It was similarly effective irrespective of the migraine frequency, and subgroup analysis suggests it was effective in those not responsive to (or intolerant of) triptans, and it seems generally well tolerated.

So is this drug a genuine step change? Potentially so. It has a longer duration of action than current acute treatments so may reduce the risk of developing chronic migraines, and it does not seem to cause medication over-use headaches, which is a massive problem in migraine management. It is the first migraine drug that can be used as both an acute and preventative treatment, meaning it could be used in a more flexible way. 

As always with new drugs we need to be mindful that there are still lots of gaps and questions that need answering. All studies were short term, most over 3-12 months, so we still don’t know if it will be effective long term or whether treatment effects will wane, and whether there will be any long term safety concerns. The current data also excluded people with chronic migraines, so it may be less effective in this group (as many treatments are). And it’s not cheap. At ~£25 for 2 tablets it is easy to see how this could be a substantial cost to the NHS, and brings into sharp focus the tension between NICE recommendations based on cost-effectiveness and affordability - cost-effectiveness (is it below the cost per quality adjusted life year/QALY threshold) does not necessarily equate to cost-saving. 

All in all, this is potentially an exciting advance in migraine treatment, but time will tell if it really is both effective and affordable, and whether it will ultimately be a drug available for use in primary care. 

I suspect these new classes of CGPR drugs are a big DEN for most of us, so if you need more of an update do join us on our new Hot Topics Course where we cover the background, evidence and guidelines for both the MABs and gepants!