The use of calcitonin gene related peptide monoclonal antibodies in the difficult to treat migraine population

Abstract

Migraine is characterised by recurrent severe unilateral headaches often associated with nausea, vomiting, phonophobia, photophobia and other neurological sequelae. It is a significant cause of morbidity, affecting an estimated 1.04 billion people worldwide and is responsible for the secondhighest number of years lived with disability worldwide. Despite the on-going development and wide availability of effective treatments for acute attacks as well as prophylaxis, there remains a significant proportion of people with migraine resistant to conventional therapies. More recently, two Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials reported efficacy for fixed, multi-site injections of onabotulinumtoxinA, which was licensed in 2010 as a rescue therapy for those patients with chronic migraine who had failed three prophylactic medications. However, despite these advances, treatmentresistant migraine remained a significant problem for both migraineurs and their treating neurologists. Since that time, advances have focused on the calcitonin gene-related peptide (CGRP), which had been known to be linked to the pathophysiology of migraine since 1990, but now offered an accessible therapeutic target. From 2015, landmark trials subsequently demonstrated efficacy and safety for monoclonal antibodies targeting CGRP (fremanezumab, erenumab, galcanezumab), but largely recruited participants with standard migraine rather than the resistant and difficult to treat migraineurs, who would represent the most likely clinical target for these therapies. This month’s journal club reviews three further phase 3b clinical trials of these agents, which focus on migraine patients failing conventional therapies.