Switching from ligand to receptor anti-calcitonin gene-related peptide (CGRP) antibodies or vice versa in non-responders: A controlled cohort study

Eur J Neurol. 2025 Jan;32(1):e16542. doi: 10.1111/ene.16542. Epub 2024 Nov 28.

Abstract

Background and purpose: Limited options exist for migraine prevention after stopping anti-calcitonin gene-related peptide monoclonal antibodies. A systematic review examining the benefits of switching between different classes (ligand vs. receptor monoclonal antibody) is essential, alongside well-designed real-world studies.

Methods: In this cohort study 67 patients were included, who discontinued their first treatment with erenumab or fremanezumab. Patients (n = 31) switched to another monoclonal antibody class within 3 months, whilst those in the control group (n = 36) received standard care. Allocation to either group relied largely on the availability of alternative monoclonal antibody treatments, introducing pseudo-random allocation. Changes in monthly migraine days were compared between groups 3 months post-discontinuation of the first monoclonal antibody or initiation of a different monoclonal antibody class. A multivariate regression model was conducted that accounted for potential confounding factors.

Results: The groups were comparable at baseline and poor treatment response was the main reason for treatment discontinuation of the first monoclonal antibody. The switching cohort experienced a reduction of 3.9 monthly migraine days (95% confidence interval -6.4, -1.3, p = 0.004) compared with the control group.

Conclusion: Transitioning to a different anti-calcitonin gene-related peptide monoclonal class yields reduction in monthly migraine days compared to returning to standard care for patients with inadequate initial treatment response.

Keywords: calcitonin gene‐related peptide; migraine; monoclonal antibodies; narrative review; preventive treatment; refractory migraine; switch.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Calcitonin Gene-Related Peptide Receptor Antagonists / administration & dosage
  • Calcitonin Gene-Related Peptide Receptor Antagonists / therapeutic use
  • Calcitonin Gene-Related Peptide* / antagonists & inhibitors
  • Calcitonin Gene-Related Peptide* / immunology
  • Cohort Studies
  • Drug Substitution
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders* / drug therapy

Substances

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