Trial Finds Erenumab Superior to Topiramate in Tolerability, Efficacy Among Migraineurs

Results of a phase 4 study show erenumab to be superior in efficacy and tolerability outcomes among migraineurs compared with topiramate.

New findings from a phase 4 study reveal Aimovig (erenumab) resulted in superior tolerability and efficacy outcomes compared with topiramate for migraine prevention.

Erenumab is a fully human monoclonal antibody, first approved in 2018, that is administered monthly via self-injection of a 70- or 140-mg dose. It works to block the calcitonin gene-related peptide (CGRP) receptor, which is believed to play a crucial role in the pathophysiology of migraine. Topiramate is one of the most used first-line therapies for migraine.

Previous research revealed close to 30% of US migraineurs discontinue migraine treatment after around 6 months, due in large part to adverse effects (AEs), the authors explained. In addition, “since evidence of comparative efficacy is limited, the therapeutic decisions are usually based on medication side effect profiles, patient characteristics, and comorbidities,” they said.

To compare the tolerability and efficacy of erenumab and topiramate, the investigators carried out a double-blind, double-dummy trial among patients who reported at least 4 migraine days per month and who had never received treatment with topiramate or a monoclonal antibody targeting the CGRP pathway.

The randomized, controlled, Head-to-head Study of Erenumab Against Topiramate in Patients With Episodic and Chronic Migraine (HER-MES) was conducted over 24 weeks at 82 sites in Germany to assess tolerability and efficacy in a patient-centered setting .

The trial included a screening phase, baseline phase, randomized treatment phase, and safety follow-up phase, while all participants were between the ages 18 and 65 years. “The 24-week double-blind treatment phase (DBTP) comprised an uptitration phase of 6 weeks with weekly visits followed by a maintenance phase with visits at weeks 8, 12, 16, 20 and 24,” the researchers explained.

Discontinuation of treatment due to an AE during the double-blind phase was the primary end point of the study. “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 end point,” the authors added.

Of the 777 patients randomized between February 2019 and July 2020, 95.1% completed the trial.

Analyses revealed:

  • In the erenumab group, 10.6% discontinued medication due to AEs compared with 38.9% in the topiramate group (odds ratio [OR], 0.19; 95% CI, 0.13-0.27; P < .001)
  • Over the course of the DBTP only 1 patient from the total population who received erenumab terminated medication due to lack of efficacy.
  • Significantly more patients achieved a ≥50% reduction in monthly migraine days from baseline with erenumab (55.4% vs. 31.2%; OR, 2.76; 95% CI, 2.06-3.71; P < .001)
  • Patients in the erenumab group reported a significantly larger reduction for both assessed quality of life questionnaires
  • Study treatment-related AEs were more frequent in the topiramate group than in the erenumab group (81.2% vs. 55.4%)
  • No new safety signals occurred

Among patients who received topiramate, the most frequently reported AEs that led to discontinuation included paraesthesia, disturbance in attention, fatigue, and nausea. In comparison, those who received erenumab reported AEs that included fatigue, nausea, disturbance in attention, and dizziness.

Importantly, during the last 3 months of the DBTP, more participants were on erenumab than topiramate, leading to better outcomes. This factor underscores the “importance of a good tolerability profile in achieving best possible results in migraine prevention,” the authors noted.

Overall. “HER-MES supports the potential of erenumab in overcoming issues of low adherence in clinical practice observed with topiramate, lessening migraine burden and improving quality of life in a broad migraine population,” they concluded.

The study was funded by Novartis while erenumab was developed by Amgen and Novartis.

Reference

Reuter U, Ehrlich M, Gendolla A, et al. Erenumab versus topiramate for the prevention of migraine – a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia. Published online November 7, 2021. doi:10.1177/03331024211053571