Switching from a CGRP ligand antibody to the receptor antibody erenumab helped 45% of previously treatment-resistant migraine patients at 6 months, reducing headache days by an average of 7 per month.
45% response at 6 monthsNearly half of migraine patients who failed CGRP ligand antibodies responded to the receptor-targeting antibody erenumab within 6 months — with the response rate increasing from 35% at 3 months, suggesting patience is warranted.
What the researchers found
Among 20 migraine patients who failed CGRP ligand antibodies (galcanezumab or fremanezumab), switching to the CGRP receptor antibody erenumab produced meaningful results: 35% responded at 3 months and 45% responded at 6 months (≥30% reduction in monthly headache days). Monthly headache days decreased from a baseline of 18.6 by 4.1 days at 3 months and 7.0 days at 6 months (both p<0.001). The improving response over time suggests that some patients may need longer than 3 months to benefit from the switch. No demographic or headache characteristics predicted who would respond.
Why it matters
When a patient doesn't respond to one anti-CGRP antibody, clinicians face a decision: try a different mechanism (receptor-targeting vs. ligand-targeting) or abandon CGRP therapy entirely. This study — along with data showing the reverse switch also works — demonstrates that the two CGRP antibody classes are not interchangeable, and failure on one doesn't mean failure on the other. The increasing response rate from 35% at 3 months to 45% at 6 months also argues for patience before declaring treatment failure.
The numbers in context
n=20 · 35% response at 3 months · 45% response at 6 months · -4.1 headache days at 3 months · -7.0 headache days at 6 months · p<0.001 · Baseline: 18.6 headache days/month
How the study worked
Retrospective single-center cohort study of patients with episodic or chronic migraine who were non-responders to galcanezumab or fremanezumab (<30% reduction in monthly headache days after 3 months) and subsequently switched to erenumab for at least 3 administrations. Monthly headache days were extracted from headache diaries. Response rates (≥30% reduction) and absolute headache day reductions were assessed at 3 and 6 months.
Who was studied
20 migraine patients who failed CGRP ligand antibodies (galcanezumab or fremanezumab) and switched to the receptor antibody erenumab
What this study cannot tell us
This is a small (n=20), retrospective, single-center study without a control group. The non-response definition (<30% reduction at month 3) may exclude partial responders who might have improved with longer treatment. Only 14 of 20 patients continued to 6 months, introducing potential attrition bias. The study can't distinguish whether improvement was due to the switch versus natural disease fluctuation or regression to the mean. No predictors of response were identified, limiting personalized treatment guidance.
How to read the evidence
This is a small, retrospective, single-center cohort study without a control group. While the statistically significant reduction in headache days (p<0.001) is encouraging, the study design cannot rule out regression to the mean or natural disease fluctuation. The increasing response over time is notable but could reflect attrition of non-responders.
When this study was published
Published in 2023, this study is recent and directly relevant to current clinical practice as headache specialists increasingly navigate the question of switching between CGRP antibody classes in non-responders.
The bigger picture
The anti-CGRP antibody landscape includes two distinct mechanisms: ligand-targeting (fremanezumab, galcanezumab bind CGRP itself) and receptor-targeting (erenumab blocks the CGRP receptor). This study, combined with data showing the reverse switch (receptor→ligand) also helps, establishes that these mechanisms are clinically distinct — not interchangeable. This has important implications for treatment algorithms: patients should try both mechanisms before giving up on CGRP-targeted prevention, potentially extending effective treatment to more people.
Questions still open
- Why does switching between CGRP antibody classes work — are there biological differences in how ligand-binding versus receptor-blocking affects the CGRP pathway?
- Can biomarkers or clinical features predict which patients will respond to the switch, enabling more personalized treatment?
- Would the response rate continue to increase beyond 6 months, or does it plateau?
Common questions
If one CGRP antibody didn't work for my migraines, should I try another?
How long should I try the new antibody before deciding if it works?
Read the original research
Effect of switching to erenumab in non-responders to a CGRP ligand antibody treatment in migraine: A real-world cohort study.
Frontiers in neurology, 14, 1154420
Citation
Overeem, Lucas Hendrik; Lange, Kristin Sophie; Fitzek, Mira Pauline; Siebert, Anke; Steinicke, Maureen; Triller, Paul; Hong, Ja Bin; Reuter, Uwe; Raffaelli, Bianca. (2023). Effect of switching to erenumab in non-responders to a CGRP ligand antibody treatment in migraine: A real-world cohort study.. Frontiers in neurology, 14, 1154420. https://doi.org/10.3389/fneur.2023.1154420