Anti-CGRP antibodies and gepants are effective migraine preventives for patients who failed prior therapies, with emerging strategies for switching, combining, and timing treatment.
4 anti-CGRP antibodies supported by high-quality evidenceAll available anti-CGRP monoclonal antibodies demonstrate efficacy in patients who have failed previous migraine preventive therapies
What the researchers found
High-quality evidence supports all four available anti-CGRP receptor monoclonal antibodies (erenumab, galcanezumab, fremanezumab, and eptinezumab) for migraine prevention in patients who have failed prior prophylactic therapies. Switching from one anti-CGRP antibody to another may benefit some non-responders. Evidence is currently insufficient to confirm or reject the efficacy of combining CGRP-targeting drugs with oral prophylactics or botulinum toxin A. Treatment termination strategies remain guided primarily by reimbursement policies rather than clinical evidence.
Why it matters
Before CGRP-targeting drugs, many migraine patients cycled through repurposed medications (blood pressure drugs, antidepressants, anticonvulsants) that weren't designed for migraine and often failed or caused intolerable side effects. CGRP-targeting therapies are the first migraine-specific preventive drugs, representing a paradigm shift. This review addresses the practical questions clinicians face when using these drugs in patients with the most treatment-resistant migraines.
How the study worked
Narrative review of published literature on CGRP-targeting migraine prophylactics, focusing on real-world clinical scenarios: non-response to prior therapy, combination therapy, switching between drugs, and treatment termination. Where published evidence was lacking, the authors provided recommendations based on clinical reasoning and expert opinion.
What this study cannot tell us
This is a narrative review, not a systematic review or meta-analysis, so the evidence selection may be subject to author bias. Much of the practical guidance on switching, combining, and terminating treatment is based on clinical reasoning rather than randomized controlled trials. Real-world effectiveness may differ from clinical trial results. The review acknowledges that evidence gaps remain significant for several key clinical questions.
How to read the evidence
This is a narrative review incorporating high-quality randomized controlled trial data for anti-CGRP efficacy in non-responders, but relying on expert opinion for many practical recommendations. The evidence base is strongest for initial drug efficacy and weakest for switching, combination, and termination strategies.
When this study was published
Published in 2023 in Cephalalgia, this review captures the state of evidence during the early maturity of CGRP-targeting therapies. Newer data on switching and combination strategies may have emerged since publication.
The bigger picture
The development of CGRP-targeting therapies represents one of the biggest advances in headache medicine in decades. CGRP is a neuropeptide released during migraine attacks that causes blood vessel dilation and pain signaling in the brain. By specifically blocking this peptide or its receptor, these drugs address the underlying biology of migraine rather than suppressing symptoms nonspecifically. The field is now moving from proving these drugs work to optimizing how they're used in clinical practice.
Questions still open
- What is the optimal duration of anti-CGRP therapy before attempting treatment discontinuation?
- Which patient characteristics predict who will respond to switching from one anti-CGRP antibody to another?
- Does combining anti-CGRP drugs with botulinum toxin provide additive benefits for chronic migraine?
Common questions
What are CGRP-targeting migraine drugs and how do they work?
What should you do if one anti-CGRP migraine drug doesn't work?
Read the original research
New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy.
Cephalalgia : an international journal of headache, 43(2), 3331024221146315
Citation
Lee, Mi Ji; Al-Karagholi, Mohammad Al-Mahdi; Reuter, Uwe. (2023). New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy.. Cephalalgia : an international journal of headache, 43(2), 3331024221146315. https://doi.org/10.1177/03331024221146315