Small-molecule CGRP receptor antagonists (gepants) deserve wider use in acute migraine treatment but financial barriers to access remain, an expert review has concluded.
Gepants are particularly appropriate for patients who cannot use triptans due to cardiovascular contraindications, tolerability concerns and risk of medication-overuse headache, according to a paper co-authored by Professor Peter Goadsby of King’s College London.
The narrative review, published in Headache journal (link here) and sponsored by AbbVie, found that gepants represented a novel treatment option for acute migraine, with clinical efficacy demonstrated in clinical trials and real world use.
Due to the favorable tolerability profile of gepants, those with migraine may be more willing to treat an attack early in its course while pain is mild or during prodromes that are reliably associated with the onset of migraine headaches.
“Gepants have demonstrated efficacy and tolerability in triptan insufficient responders, perhaps because of their distinct mechanisms of action,” the authors noted.
These clinical trials had also shown that gepants had a good safety profile without the cardiovascular risks or potential for medical overuse headache seen with triptans, although they have drug interactions due to their hepatic metabolism via the cytochrome P450 3A4 pathway.
Unlike triptans there was also emerging evidence of efficacy of at least one gepant (ubrogepant) in preventing headache onset when given during the prodrome, the review found.
The evidence of efficacy and the safety and tolerability advantages suggested that gepants be a first-line treatment option for the acute treatment of migraine, they concluded.
“Due to the favorable tolerability profile of gepants, those with migraine may be more willing to treat an attack early in its course while pain is mild or during prodromes that are reliably associated with the onset of migraine headaches,” they wrote.
“In appropriately selected patients, these advantages may optimise patient care and lead to better persistence and efficacy outcomes in a real-world setting,” they added.
However, the review authors cautioned that specifically designed head-to- head studies were still needed to assess the comparative effectiveness of triptans and gepants.
And in the real world settings a major barrier to use of gepants in acute migraine was the “markedly higher” cost compared to triptans , the review authors said.
“In light of the higher costs of gepants versus triptans, efforts should be made to increase access to and lower the costs of gepants for patients with migraine for whom triptans are ineffective or are contraindicated,” they suggested.
“Furthermore, for patients with chronic migraine, the direct costs of CGRP-targeted therapies should be considered in the context of reducing overall healthcare resource utilization and improving treatment adherence.”
In Australia, rimegepant (Nurtec) has been available for the treatment of acute migraine since July 2023, but is not available on the PBS. According to Migraine Australia it is available on private prescription with an estimated costs of around $62 for 2 x 75mg tablets. Another gepant, atogepant (Aquipta), has been approved by the TGA for migraine prophylaxis but is not yet available in Australia.