Erenumab versus topiramate for the prevention of migraine – a randomised, double-blind, active-controlled phase 4 trial

Abstract

Background We compared the tolerability and efficacy of erenumab, a monoclonal antibody binding to the calcitonin gene-related peptide 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 and naïve to study drugs were randomly assigned (1:1) to either subcutaneous erenumab (70 or 140 mg/month) plus topiramate placebo (erenumab group) or oral topiramate at the individual dose with optimal efficacy (50–100 mg/day) plus erenumab placebo (topiramate group). The primary endpoint was medication discontinuation due to an adverse event during the double-blind phase. The proportion of patients that achieved ≥50% reduction from baseline in monthly migraine days during the last 3 months of the double-blind phase was a secondary endpoint. Results Seven hundred and seventy-seven patients were randomised (from 22 February 2019 to 29 July, 2020) and 95.1% completed the study. 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 0.13–0.27; p < 0.001). Significantly more patients achieved a ≥50% reduction in monthly migraine days from baseline with erenumab (55.4% vs. 31.2%; odds ratio 2.76; 95% confidence interval 2.06–3.71; p < 0.001). No new safety signals occurred. Conclusions Erenumab demonstrated a favourable tolerability and efficacy profile compared to topiramate. Trial registration: ClinicalTrials.gov NCT03828539, URL: https://clinicaltrials.gov/ct2/show/NCT03828539

Migraine Prevention with Erenumab: Focus on Patient Selection, Perspectives and Outcomes

“…In few cases the reason for discontinuation was an adverse event. Overall, proportion of erenumab discontinuation is similar to onabotulinumtoxinA, but remarkably lower than topiramate, 34 , 62 which showed a lower tolerability profile.…”

“…Proportion of AEs was lower in erenumab compared with topiramate group (55.4% vs 81.2%); most common AEs were paresthesia, disturbance in attention, fatigue and nausea in the topiramate group and fatigue, nausea, disturbance in attention and dizziness in the erenumab group. 34 …”

Long‐term adherence, safety, and efficacy of repeated onabotulinumtoxinA over five years in chronic migraine prophylaxis

“…28,29 Notably, discontinuation rates were much lower with BoNTA and erenumab than with topiramate after 36 and 24 weeks of treatment, respectively. 28,29 Indeed, maintaining long-term adherence defined as the active choice in which patients are following through with the prescribed treatment while taking responsibility for their own well-being, 30 remains suboptimal in the setting of migraine prophylaxis. 31 Toward the latter view, the primary objective of the current study was to evaluate the long-term adherence to repeated BoNTA treatment over five years and then to assess its long-term safety/ efficacy and patients' satisfaction.…”

“…27 Nonetheless, head-to-head comparisons of topiramate, that is, the standard-of-care in CM prophylaxis, versus both BoNTA and erenumab-the latter being a monoclonal antibody (MAbs) against calcitonin gene related peptide (CGRP) receptor, have proved superiority of both BoNTA and erenumab over topiramate in terms of efficacy, safety, and tolerance. 28,29 Notably, discontinuation rates were much lower with BoNTA and erenumab than with topiramate after 36 and 24 weeks of treatment, respectively. 28,29 Indeed, maintaining long-term adherence defined as the active choice in which patients are following through with the prescribed treatment while taking responsibility for their own well-being, 30 remains suboptimal in the setting of migraine prophylaxis.…”

Calcitonin Gene-Related Peptide (CGRP)-Targeted Monoclonal Antibodies and Antagonists in Migraine: Current Evidence and Rationale

“…A phase IV RCT aimed to compare the tolerability and efficacy of erenumab to topiramate as migraine preventive treatment. The primary outcome was rate of discontinuation, which was 10.6% for patients taking erenumab compared to 38.9% of patients taking topiramate ( p < 0.001) [ 27 ]. Additionally, adverse events (AEs) were more common in patients taking topiramate than in patients taking erenumab (81.2% vs. 55.4%, respectively),…”