Erenumab Versus Topiramate for the Prevention of Migraine – A Randomised, Double-Blind, Active-Controlled Phase 4 Trial

Abstract

Background: Migraine prophylaxis with oral medications is often compromised by intolerable side effects. We compared the tolerability and efficacy of erenumab, a monoclonal antibody binding to the calcitonin gene-related peptide (CGRP) receptor, to topiramate for migraine prophylaxis in adults. Methods: HER-MES was a 24-week, randomised, double-blind, double-dummy, controlled trial conducted in 82 sites in Germany. Patients with ≥ 4 migraine days per month who were naive to study drugs were randomly assigned (1:1) to either subcutaneous erenumab (70 or 140 mg/month) or oral topiramate at highest tolerated dose (50–100 mg/day). Randomisation and allocation were done via an interactive response system. Randomisation was stratified by monthly migraine days (MMD: 4–7, 8–14, ≥ 15). Masking was achieved by administration of matching placebo. Patients, investigators, and the sponsor were blinded to treatment.The primary endpoint was the proportion of patients who discontinued study medication due to an adverse event during the double-blind phase. Secondary efficacy endpoints included the proportion of patients that achieved at least a 50% reduction from baseline in MMD. The full analysis set (FAS) included all participants who received at least one dose of study drug. The HER-MES study is registered with ClinicalTrials.gov (NCT03828539). Findings: The study was conducted from February 22, 2019 to July 29, 2020. 777 patients were randomised and 95·1% completed the study. The FAS comprised 776 patients (388 in each group) of which 59·1% were naive to prophylaxis. In the erenumab group, 10·6% discontinued medication due to adverse events compared to 38·9% in the topiramate group (odds ratio, 0·19; 95% confidence interval [CI] 0·13 to 0·27; p<0·001). Significantly more patients achieved a ≥ 50% reduction in MMD from baseline with erenumab (55·4% vs. 31·2%). No new safety signals occurred. Interpretation: Erenumab demonstrated a favourable tolerability and efficacy profile compared to topiramate. Trial Registration: NCT03828539 Funding: Novartis. Declaration of Interests: Dr. Reuter reports other from Novartis, during the conduct of the study; personal fees and non-financial support from Amgen, personal fees from Abbvie, personal fees, non-financial support and other from Allergan, other from Alder, personal fees, non-financial support and other from Eli Lilly, personal fees and non-financial support from Medscape, grants, personal fees and non-financial support from Novartis, personal fees and non-financial support from StreaMedUp, personal fees and non-financial support from Teva Pharmaceutical, outside the submitted work; Ch. Sieder is an employee of Novartis Pharma; Dr. Ehrlich reports other from Novartis Pharma GmbH, during the conduct of the study; Dr. Gendolla reports, other from Novartis, during the conduct of the study; personal fees and non financial support from Allergan, personal fees and non-financial support and other from Eli Lilly, personal fees from Esanum , personal fees and non-financial support from Novartis, personal fees and non-financial support from Teva Pharmaceutical, Grunenthal ,Mundipharma and DGS outside the submitted work; Dr. Heinze reports personal fees from Novartis, during the conduct of the study; personal fees from Teva, personal fees from Ely Lilly, personal fees from Novartis, outside the submitted work; Ch. Sieder is an employee of Novartis Pharma; Dr. Hentschke reports other from Novartis Pharma , during the conduct of the study; Dr. Reuter reports other from Novartis, during the conduct of the study; personal fees and non-financial support from Amgen, personal fees from Abbvie, personal fees, non-financial support and other from Allergan, other from Alder, personal fees, non-financial support and other from Eli Lilly, personal fees and non-financial support from Medscape, grants, personal fees and non-financial support from Novartis, personal fees and non-financial support from StreaMedUp, personal fees and non-financial support from Teva Pharmaceutical, outside the submitted work; Dr. Ehrlich reports other from Novartis Pharma GmbH, during the conduct of the study. Ethics Approval Statement: Independent ethics committees at each trial centre approved the study protocol and its amendments.