Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine: A pooled analysis of four placebo-controlled trials with long-term extensions

Cephalalgia. 2019 Dec;39(14):1798-1808. doi: 10.1177/0333102419888222. Epub 2019 Nov 10.

Abstract

Background: Efficacy and safety of erenumab have been evaluated in a comprehensive clinical development program resulting in approval for migraine prevention in over 40 countries to date.

Methods: This integrated safety analysis included four double-blind randomized trials and their extensions (up to three-plus years). Safety endpoints included exposure-adjusted patient incidences of adverse events, serious adverse events, and anti-erenumab antibodies.

Results: In all, 2375 of the patients randomized across the four studies received at least one dose of erenumab (70 mg or 140 mg), with cumulative exposure of 2641.2 patient-years. Exposure-adjusted adverse event rates during the double-blind treatment phase were similar to placebo, with the exception of injection-site reactions (17.1 vs. 10.8 per 100 patient-years), constipation (7.0 vs. 3.8 per 100 patient-years), and muscle spasm (2.3 vs. 1.2 per 100 patient-years). During the long-term extensions, adverse events reported were similar to those observed during the double-blind treatment phase, and rates of injection site reactions, constipation, and muscle spasm were reported at lower rates than in the double-blind treatment phase. There were two deaths reported, both confounded by pre-existing conditions.

Conclusions: This pooled safety analysis revealed a favorable and stable adverse event profile over time for erenumab with more than three years of exposure.

Trial registration: ClinicalTrials.gov NCT01952574, NCT02483585, NCT02456740, NCT02066415, and NCT02174861.

Keywords: Erenumab; migraine; safety.

Publication types

  • Meta-Analysis

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Calcitonin Gene-Related Peptide Receptor Antagonists / adverse effects
  • Calcitonin Gene-Related Peptide Receptor Antagonists / therapeutic use*
  • Fatigue / chemically induced
  • Female
  • Humans
  • Male
  • Migraine Disorders / diagnosis
  • Migraine Disorders / prevention & control*
  • Nausea / chemically induced
  • Randomized Controlled Trials as Topic / methods*
  • Time Factors

Substances

  • Antibodies, Monoclonal, Humanized
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • erenumab

Associated data

  • ClinicalTrials.gov/NCT01952574
  • ClinicalTrials.gov/NCT02066415
  • ClinicalTrials.gov/NCT02483585
  • ClinicalTrials.gov/NCT02456740
  • ClinicalTrials.gov/NCT02174861