The European Headache Federation recommends all four anti-CGRP monoclonal antibodies for migraine prevention, based on low-to-high quality evidence for both episodic and chronic migraine.
4 drugs recommendedAll four anti-CGRP monoclonal antibodies received positive recommendations for migraine prevention based on formal evidence review
What the researchers found
The European Headache Federation formally recommends all four anti-CGRP monoclonal antibodies for migraine prevention. For episodic migraine, eptinezumab, erenumab, fremanezumab, and galcanezumab are recommended based on low to high quality evidence. For chronic migraine, erenumab, fremanezumab, and galcanezumab are recommended based on medium to high quality evidence.
One antibody (erenumab) targets the CGRP receptor, while the other three (eptinezumab, fremanezumab, galcanezumab) target the CGRP peptide itself. The guideline notes that for many clinical questions — like which patients to prioritize, when to switch between drugs, or how long to treat — evidence was insufficient and recommendations relied on expert opinion.
Why it matters
This was the first official European guideline for anti-CGRP monoclonal antibodies in migraine, establishing them as evidence-based preventive treatments. CGRP is a peptide that plays a central role in migraine pathophysiology, and these antibodies represented the first migraine-specific preventive therapy class. The guideline gave clinicians an evidence-based framework for prescribing these drugs, which have since become a standard of care for patients who don't respond to traditional preventives.
The numbers in context
4 monoclonal antibodies evaluated · Low–high quality evidence for episodic migraine · Medium–high quality evidence for chronic migraine · 1 targets CGRP receptor (erenumab) · 3 target CGRP peptide (eptinezumab, fremanezumab, galcanezumab)
How the study worked
The guideline was developed using the GRADE (Grading of Recommendation, Assessment, Development, and Evaluation) approach. The working group performed systematic literature review, assessed evidence quality, and formulated recommendations. Where evidence was insufficient for GRADE-based recommendations, expert opinion was used.
Who was studied
Patients with episodic and chronic migraine considered for preventive treatment
What this study cannot tell us
Published in 2019, this guideline reflects early-stage evidence for these drugs — long-term safety and real-world effectiveness data were limited at the time. Several clinical questions (patient selection, switching between drugs, treatment duration) lacked sufficient evidence for formal recommendations. The guideline has likely been updated or supplemented since publication.
How to read the evidence
Strong evidence grade — this is a formal clinical practice guideline from a major professional society using GRADE methodology, the gold standard for evidence assessment. It synthesizes data from multiple randomized controlled trials.
When this study was published
Published in 2019. While this was groundbreaking as the first European anti-CGRP guideline, the evidence base has grown substantially since then. Updated guidelines and real-world data have supplemented these initial recommendations.
The bigger picture
Anti-CGRP monoclonal antibodies were the first migraine-specific preventive treatments ever developed — previous options were all repurposed from other conditions (blood pressure drugs, antidepressants, anti-seizure medications). This guideline marked a turning point in migraine treatment, formally endorsing targeted peptide-pathway therapies. Since then, these drugs have become widely prescribed and the anti-CGRP class has expanded to include small-molecule CGRP receptor antagonists (gepants) for both prevention and acute treatment.
Questions still open
- How have real-world data since 2019 changed recommendations for patient selection and treatment duration?
- Which patients should receive anti-CGRP receptor antibodies (erenumab) versus anti-CGRP peptide antibodies?
- What is the long-term cardiovascular safety of chronically blocking CGRP, a peptide involved in vascular regulation?
Common questions
What is CGRP and why does blocking it prevent migraines?
Which anti-CGRP drug should a migraine patient choose?
Read the original research
European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention.
The journal of headache and pain, 20(1), 6
Citation
Sacco, Simona; Bendtsen, Lars; Ashina, Messoud; Reuter, Uwe; Terwindt, Gisela; Mitsikostas, Dimos-Dimitrios; Martelletti, Paolo. (2019). European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention.. The journal of headache and pain, 20(1), 6. https://doi.org/10.1186/s10194-018-0955-y