Second-generation gepants in the treatment of migraine – a review of the findings of randomised controlled trials

Abstract

Pharmacological treatment of migraine may be either acute (abortive) or preventive (prophylactic), though patients with frequent migraine attacks may require both. The aim of acute treatment is to treat attacks quickly and consistently, prevent recurrences, and restore patients to normal functioning. The goal of preventive migraine therapy is to reduce the frequency, duration, and severity of attacks. Calcitonin gene-related peptide (CGRP) is a neuropeptide which plays a critical role in migraine pathophysiology. The first CGRP antagonist studied in patients with migraine was olcegepant. Despite the fact that the efficacy of CGRP antagonists in the treatment of migraine has been demonstrated in clinical trials, further research on CGRP antagonists has been suspended due to safety concerns related to their toxic effects on the liver. In recent years, newgeneration gepants have been developed. The efficacy of rimegepant and ubrogepant as acute migraine medications, as well as atogepant and rimegepant as migraine preventives, has been confirmed in randomised placebo-controlled phase three studies. The most commonly reported treatment-related emergent adverse events of gepants include nausea and constipation. No cardiovascular or hepatic adverse events have emerged so far. CGRP antagonists do not exhibit vasoconstrictive proprieties. Gepants may be used in patients with cardiovascular diseases when triptans are contraindicated. The results of studies investigating the efficacy and tolerability of CGRP antagonists are promising and it is hoped that in the future they will broaden the range of abortive and prophylactic options for the management of migraine.