Erenumab versus topiramate for the prevention of migraine

Reuter U, Ehrlich M, Gendolla A, et al. Erenumab versus topiramate for the prevention of migraine—a randomized, double-blind, active-controlled phase 4 trial. Cephalagia. 2022;42(2):108-118. doi:10.1177/03331024211053571

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.

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For the treatment and prevention of migraine episodes, erenumab was found to have a higher tolerability versus topiramte among patients. The results from the HER-MES trial, funded by Novartis, were published in Cephalagia, a journal published monthly on behalf of the International Headache Society.

The HER-MES trial was a 24-week, randomized, double-blind, double-dummy, controlled trial conducted across 82 sites in Germany. Whereas previous studies have confirmed the efficacy of both erenumab and topiramate for the treatment of migraine against placebo, the primary endpoint of the HER-MES trial was the rate of medication discontinuation due to adverse events experienced during treatment. The secondary endpoint was the number of patients who achieved a 50% or higher reduction in monthly migraine days from baseline.

“Tolerability is a prerequisite for an effective migraine drug to achieve meaningful improvement in a broad migraine population,” the authors observed. “Thus, our primary objective was to compare the tolerability of topiramate and erenumab measured as the rate of medication discontinuation due to [adverse effects].”

A total of 777 patients with a history of migraine with or without aura who had never received treatment with either topiramate or a monoclonal antibody like erenumab were enrolled. Patients were randomly assigned in a 1:1 ratio to receive either topiramate verum plus an erenumab placebo or erenumab verum plus a topiramate placebo.

Patients tracked and recorded information about migraine and nonmigraine headaches experienced during the trial and completed several questionnaires to track outcomes including:

• Medical outcome short form health survey version 2 (SF-36v2);
• Headache impact test (HIT-6);
• Treatment satisfaction questionnaire for medication (TSQM);
• Beck Depression Inventory (BDI-II).

Adverse effects were assessed during regular visits.

Of the study participants, 95.1% completed the study. For the erenumab group, 10.6% of participants discontinued the medication due to adverse effects compared to 38.9% in the topiramate group (odds ratio, 0.19; 95% confidence interval 0.13-0.27; p<0.001). The most common adverse effects that led to discontinuation for the topiramate group were paranesthesia, attention disturbance, fatigue, and nausea. For the erenumab group, these were fatigue, nausea, attention disturbance, and dizziness.

In the erenumab group, 55.4% of patients achieved a 50% or greater reduction in monthly migraine days versus 31.2% for the topiramate group (odds ratio 2.76; 95% confidence interval 2.06-3.71; p<0.001).

“Compared to topiramate, treatment with erenumab has a superior tolerability profile and a significantly higher efficacy. 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,” the researchers concluded.

https://www.hmpgloballearningnetwork.com/site/neuro/news/migraine-prevention-tolerability-higher-erenumab-versus-topiramate