Although there are still gaps in our understanding of migraine pathophysiology, the neuropeptide Calcitonin Gene-Related Peptide (CGRP) plays a key role. This has driven development of CGRP blockers as a new approach to preventing migraine.
The pathophysiology of migraine is thought to involve the vasculature, central and peripheral neuronal pathways involved in pain signalling, as well as inflammation.
A number of lines of evidence support the role of CGRP in migraine.
- CGRP levels (both peripherally and centrally) increase during a severe migraine attack
- Elevated CGRP levels during a migraine attack are normalized with effective triptan treatment
- Intravenous infusion of CGRP can induce migraine-like attacks in patients with a history of migraine
- Administration of CGRP receptor antagonists has been shown to abort an attack
Thus, recognition of the role of CGRP in migraine pathophysiology has driven the development of new agents specifically targeting CGRP or its receptor. Unlike other preventive therapies for migraine, these agents target specific migraine mechanisms and do not appear to have vasoconstrictive effects. The latter point is important, as these new treatments may therefore be suitable for use in patients with established cardiovascular disease.
Agents that block CGRP include monoclonal antibodies to CGRP or its receptor, erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality) and eptinezumab (Vyepti) and the CGRP receptor antagonists or 'gepants', rimegepant (Nurtec ODT/Vydura), ubrogepant (Ubrelvy) and atogepant (Qulipta).
Some currently available agents are being investigated in other indications, and other novel agents that target CGRP are in development.