ERENUMAB, A NEW PREVENTIVE TREATMENT FOR MIGRAINE: MECHANISM OF ACTION, SAFETY AND EFFICACY

Abstract

Background: Migraine is a common, debilitating and one of the most disabling of the neurovascular disorders. The common treatment has been based on non-specific medications derived from other clinical disciplines such as beta-blockers, antiepileptics and antidepressants, which have variable efficacy and many unwanted side effects and are therefore frequently discontinued. The recent knowledge about the involvement of CGRP and its receptors in migraine pathophysiology has opened new avenues for anti-migraine treatment. Objectives: The aim of this paper is to comprehensively review the mechanism of action, clinical efficacy, safety profile, and comparative effectiveness of erenumab - the first fully human monoclonal antibody designed specifically for migraine prevention. Methods: A narrative review of the current medical literature was conducted using the PubMed database. The analysis included data from phase 2, 3 and 4 randomized controlled trials, long-term open-label extensions, and current international neurological guidelines. Results: Erenumab is a monoclonal antibody that selectively targets the canonical CGRP receptor and functions as a competitive receptor antagonist. Binding of erenumab to the CGRP receptor does not result in vasoconstriction and does not interact with the CYP450 enzyme system. Studies including STRIVE, ARISE and LIBERTY trials have demonstrated the high efficacy of erenumab in the reduction of MMD in both EM and CM patients, including those who have failed multiple prior prophylactic treatments. The HER-MES trial has further confirmed the high tolerability of erenumab and a higher retention rate compared to topiramate. The safety profile is highly favorable, with injection site reactions and constipation being the most frequently reported adverse events. Furthermore, erenumab can safely be given alongside with novel acute treatments, such as gepants and ditans. Conclusions: Erenumab holds great promise in migraine prophylaxis as it’s offering a targeted, highly effective, and well-tolerated therapeutic option. Future research should focus on its long-term efficacy in a real-world setting. One important aspect will be to explore its safety during pregnancy and in children. An interesting and potentially clinically useful aspect for non-responders will be exploring the possibility of combining it with antibodies against other neuropeptide pathways, such as those involving PACAP.