Among migraine patients who failed anti-CGRP antibody treatments, 18.2% achieved at least 50% reduction in monthly headache days with atogepant after three months, and 59% reported some degree of improvement.
33.3% response for severe headachesOne-third of patients who had failed anti-CGRP antibodies achieved at least 50% reduction in moderate-to-severe headache days with atogepant — meaningful relief for a treatment-resistant population.
What the researchers found
Of 44 participants who had failed anti-CGRP monoclonal antibodies (88.6% chronic migraine), atogepant at 3 months produced:
- 18.2% achieved ≥50% reduction in monthly headache days (MHDs)
- 25.0% achieved ≥30% reduction in MHDs
- 33.3% achieved ≥50% reduction in moderate-to-severe headache days (MSHDs)
- Median MHDs decreased from 24.5 to 21.5 (p=0.011)
- Median MSHDs decreased from 15.0 to 12.0 (p=0.001)
- 59.1% reported some degree of improvement on Patient Global Impression scale
- Acute medication days and HIT-6 disability scores also significantly decreased
- Constipation occurred in 31.8%; 11.4% discontinued due to side effects
Why it matters
Patients who fail multiple anti-CGRP antibodies represent a challenging clinical population with few remaining preventive options. This study provides the first real-world evidence that switching from antibodies to atogepant — a small molecule gepant that blocks the same pathway but through a different mechanism — can still benefit a meaningful subset of these patients. This is important for clinical decision-making when antibody treatments fail.
How the study worked
This retrospective cohort study (RESCUE) screened 213 medical records and identified 44 patients with episodic or chronic migraine who discontinued anti-CGRP monoclonal antibodies (erenumab, galcanezumab, or fremanezumab) due to lack or loss of efficacy and subsequently started atogepant. Outcomes were assessed at 3 months including headache day frequency, severity, acute medication use, disability scores, patient-reported improvement, and adverse events.
What this study cannot tell us
This is a retrospective study without a control group, making it impossible to account for placebo effects or natural disease fluctuation. The sample size of 44 is relatively small. Most patients (88.6%) had chronic migraine, limiting generalizability to episodic migraine. The 3-month follow-up is relatively short. Selection bias may exist in who was offered atogepant after antibody failure. The high constipation rate (31.8%) and 11.4% discontinuation rate are notable.
How to read the evidence
This is a retrospective cohort study without a control group, providing moderate-level real-world evidence. While the results are clinically meaningful, the absence of randomization and placebo control limits causal conclusions.
When this study was published
Published in 2025, this is very timely research addressing a current clinical challenge as anti-CGRP therapies have become standard migraine prevention and clinicians increasingly face the question of what to try when they fail.
The bigger picture
The CGRP pathway can be targeted by two distinct drug classes: monoclonal antibodies (injected, targeting CGRP ligand or receptor) and gepants (oral, small-molecule receptor blockers). This study challenges the assumption that failing one class means the entire pathway is exhausted — suggesting that the different mechanisms of action may explain why some antibody non-responders still benefit from gepants. This has implications for treatment sequencing guidelines in migraine prevention.
Questions still open
- Why do some patients who fail anti-CGRP antibodies still respond to gepants — is it due to different receptor binding sites, pharmacokinetics, or other factors?
- Would longer treatment with atogepant increase the response rate in this population?
- Are there clinical or biomarker predictors of which antibody non-responders will benefit from switching to atogepant?
Common questions
If anti-CGRP antibodies didn't work for migraine, can atogepant still help?
What are the main side effects of atogepant in this population?
Read the original research
Retrospective cohort study of anti-CGRP monoclonal antibody unresponsive migraine individuals treated with atogepant: The RESCUE study.
Cephalalgia : an international journal of headache, 45(6), 3331024251346925
Citation
Jaimes, Alex; Rodríguez-Vico, Jaime; Pajares, Olga; Eguilior Caffarena, Ignacio; Nystrom Hernández, Anna Lena; Gómez, Andrea; Porta-Etessam, Jesús. (2025). Retrospective cohort study of anti-CGRP monoclonal antibody unresponsive migraine individuals treated with atogepant: The RESCUE study.. Cephalalgia : an international journal of headache, 45(6), 3331024251346925. https://doi.org/10.1177/03331024251346925