Calcitonin gene-related peptide-targeted therapy in migraine: current role and future perspectives

Almost 40 years ago, the discovery of the vasoactive neuropeptide calcitonin gene-related peptide (CGRP) and its role in migraine pathophysiology ushered in a new era in migraine treatment. Since 2018, monoclonal antibodies (mAbs) targeting the CGRP pathway are available for migraine prevention. The approval of these drugs marks a pioneering development, as they are the first pharmacological agents specifically tailored for migraine prevention. Introduction of these agents contrasts the historical reliance on traditional preventive medications initially formulated for other indications and later repurposed for migraine therapy. Although the emergence of evidence on the efficacy and safety of CGRP-targeted mAbs has raised the bar for treatment success in migraine, their efficacy in other headache entities, such as cluster headache, is low to moderate. Small-molecule CGRP receptor antagonists called gepants have also been proven to be effective both as acute and preventive migraine treatments. Furthermore, these agents have bridged the traditional categories of acute and preventive treatment strategies. Short-term prevention and treatment during the prodromal phase of migraine represent emerging strategies enabling clinicians to develop treatment approaches designed to meet changing patient needs; however, these strategies still require more formal evidence. Although solid data have been gathered, further research concerning the efficacy and long-term safety of drugs targeting the CGRP pathway and robust pharmacoeconomic evaluations are needed. Finally, randomised withdrawal and switching studies would facilitate the formulation of evidence-based guidance for the discontinuation of and switching between drugs targeting the CGRP pathway.