Migraine patients who didn't respond to one type of anti-CGRP antibody gained nearly 4 fewer migraine days per month by switching to the other type, compared to returning to standard care.
-3.9 migraine days/monthPatients who switched between anti-CGRP antibody classes (ligand vs. receptor targeting) experienced nearly 4 fewer monthly migraine days compared to those who returned to standard care after failing their first antibody.
What the researchers found
Migraine patients who didn't respond to their first anti-CGRP monoclonal antibody (either erenumab or fremanezumab) benefited from switching to the other class — ligand-targeting to receptor-targeting or vice versa. The 31 patients who switched experienced a reduction of 3.9 monthly migraine days compared to 36 control patients who returned to standard care (95% CI: -6.4 to -1.3, p = 0.004). This demonstrates that failure on one anti-CGRP antibody class doesn't mean the entire CGRP-targeting approach should be abandoned.
Why it matters
When a migraine patient doesn't respond to an anti-CGRP antibody, clinicians face a difficult decision: try the same class of drug (just a different brand), switch to a different CGRP-targeting mechanism, or abandon CGRP therapy entirely. This study provides the first controlled evidence that switching between ligand-targeting antibodies (like fremanezumab, which binds CGRP itself) and receptor-targeting antibodies (like erenumab, which blocks the CGRP receptor) can rescue patients who failed their first treatment.
The numbers in context
n=67 · Switchers: n=31 · Controls: n=36 · -3.9 monthly migraine days vs. control · 95% CI: -6.4 to -1.3 · p=0.004
How the study worked
This controlled cohort study included 67 patients who discontinued their first anti-CGRP monoclonal antibody (erenumab or fremanezumab) primarily due to poor response. Thirty-one patients switched to the other antibody class within 3 months, while 36 received standard care (controls). Allocation was pseudo-random based on treatment availability. Changes in monthly migraine days were compared at 3 months using a multivariate regression model adjusting for confounders.
Who was studied
67 migraine patients who discontinued their first anti-CGRP monoclonal antibody due to poor treatment response
What this study cannot tell us
This is a non-randomized cohort study with pseudo-random allocation based on drug availability, not true randomization. The sample size of 67 is modest. The 3-month follow-up is relatively short for assessing sustained migraine prevention. Only two anti-CGRP antibodies were studied (erenumab and fremanezumab), not galcanezumab or eptinezumab. The study cannot determine which direction of switching (ligand→receptor or receptor→ligand) is more effective.
How to read the evidence
This is a controlled cohort study with pseudo-random allocation, multivariate adjustment, and statistically significant results. It's stronger than case series but weaker than a randomized controlled trial due to the non-randomized design and modest sample size.
When this study was published
Published in 2025, this is a very recent and clinically relevant study addressing a practical question that headache specialists face regularly as anti-CGRP therapies become standard of care.
The bigger picture
The anti-CGRP antibody class includes drugs that work through two distinct mechanisms — some bind the CGRP peptide itself (fremanezumab, galcanezumab) while others block the CGRP receptor (erenumab). Until this study, it was unclear whether these mechanistic differences mattered clinically when one drug failed. The finding that switching between mechanisms helps non-responders suggests these two approaches are not biologically interchangeable and that the CGRP pathway can be targeted in meaningfully different ways.
Questions still open
- Is switching from ligand-targeting to receptor-targeting antibodies more effective than the reverse, or are both directions equally beneficial?
- Would patients who fail both antibody classes still respond to gepants (oral CGRP receptor antagonists), which work through yet another mechanism?
- What biological factors determine whether a patient responds to ligand-targeting versus receptor-targeting anti-CGRP therapy?
Common questions
What's the difference between ligand and receptor anti-CGRP antibodies?
Should I switch antibodies if my anti-CGRP medication isn't working?
Read the original research
Switching from ligand to receptor anti-calcitonin gene-related peptide (CGRP) antibodies or vice versa in non-responders: A controlled cohort study.
European journal of neurology, 32(1), e16542
Citation
van Veelen, Nancy; van der Arend, Britt W H; Hiele, E; van Zwet, E W; Terwindt, Gisela M. (2025). Switching from ligand to receptor anti-calcitonin gene-related peptide (CGRP) antibodies or vice versa in non-responders: A controlled cohort study.. European journal of neurology, 32(1), e16542. https://doi.org/10.1111/ene.16542