While there is evidence that monoclonal antibodies that act on the calcitonin gene-related peptide or its receptor can be effective for patients with chronic and episodic migraine, there is not enough evidence to provide an expert- and evidence-based guideline based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, according to a study published in the Journal of Headache and Pain.

This analysis by the European Headache Federation (EHF) had the aim of evaluating the 4 monoclonal antibodies currently developed — erenumab, which targets the calcitonin gene-related peptide receptor, and eptinezumab, fremanezumab, and galcanezumab, which target the calcitonin gene-related peptide — and providing an expert- and evidence-based guideline on the use of these drugs for migraine prevention by using the GRADE approach. The investigators identified relevant questions, performed analysis and systematic review of the literature, assessed the quality of the evidence, then wrote recommendations. Expert opinions were provided where the GRADE approach was not applicable.

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Low-to-high quality evidence was found to recommend all 4 monoclonal antibodies for patients with episodic migraine, although the benefits of eptinezumab are not fully clear, and significant improvements were seen only in the reduction of medications taken for acute attacks. The other 3 drugs reduce the number of days patients take acute medications, lower the number of headache/migraine days, and improve disability.

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Medium-to-high quality evidence was found to recommend erenumab, fremanezumab, and galcanezumab for patients with chronic migraine, as they are safe, reduce the number of headache/migraine days and the number of days patients take acute medications, as well as improve disability.  For a number of clinical questions, there was insufficient evidence to provide recommendations, according to the GRADE approach, and therefore the document’s recommendations had to rely on experts’ opinion.

Study investigators concluded that monoclonal antibodies acting on the calcitonin gene-related peptide, “appear promising drugs for migraine prevention. Real-word data will be very important to support efficacy and safety of those drugs particularly in the long-term. Future biomarker research should identify patients more prone to respond to [calcitonin gene-related peptide monoclonal antibodies] and enable clinicians to personalize treatment decisions.”


Sacco S, Bendtsen L, Ashina M, et al. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J Headache Pain. 2019;20(1):6.