A systematic review with expert opinion on the role of gepants for the preventive and abortive treatment of migraine

Introduction: Gepants are small molecules targeting the calcitonin gene-related peptide (CGRP) that have been recently introduced and are under additional clinical development as preventive and abortive treatment options for migraine.

Areas covered: After providing a narrative overview of current preventive and acute treatment options for migraine and summarizing the pathophysiology of migraine attack and the role of CGRP, we performed a systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, on trials on gepants in preventive and acute treatment of migraine. Studies and results were reviewed and discussed, and expert opinion was presented. We also collected data on relevant ongoing trials.

Expert opinion: Whether direct targeting CGRP pathways within the central nervous system or indirectly modulating them from the peripheral nervous system is more effective and safer in migraine remains still unclear. The available data on the efficacy and safety of gepants suggest they may represent an abortive, and to some extent, preventive treatment option for migraine, in patients who do not respond or have adverse effects to first/second line treatments or at high risk for medication overuse headache; thus opening new therapeutic horizons.