Decoding the long-term safety of antiCGRP (receptor) mAbs - a meta-analysis and systematic review

Sep 30, 2026

Uploaded by James

Objective To evaluate the long-term safety (≥12 months) of monoclonal antibodies targeting CGRP or its receptor in migraine prevention, synthesizing clinical trials and real-world evidence. Focus includes discontinuation due to adverse events and the adverse-event type and frequency. Methods systematically searched PubMed, Cochrane Library, and ClinicalTrials.gov for ≥12-month anti-CGRP mAb use and applied random-effects meta-analysis with ROBINS-I bias assessment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Objective

Methods

Results

Conclusion

Keywords

Introduction

Migraine burden and need for prevention

CGRP-targeted therapies and study background

Hoehne etal. The Journal of Headache and Pain (2026) 27:10 [https://doi.org/10.1186/s10194-025-02256-0](https://doi.org/10.1186/s10194-025-02256-0) The Journal of Headache and Pain REVIEW Open Access Decoding the long-term safety of antiCGRP (receptor) mAbs: a meta-analysis and systematic review Carol in Luisa Hoehne 1, Lucas Hendrik Overeem 1, Margarita Sanchez-Del-Rio2, Christiana Deligianni3,4, Raquel Gil-Gouveia5,6, Jan Versijpt7,8, Faisal Mohammad Amin9, Christian Lampl 10, Kristina Ryliskiene 11, Erling Tronvik 12,13, Gianluca Coppola 14, Philip R. Holland 15, Antoinette MaassenVanDenBrink 16, Paolo Martelletti 17, Uwe Reuter 1* and on behalf of the European Headache Federation, EHF Abstract Objective To evaluate the long-term safety (≥12 months) of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) or its receptor in migraine prevention by synthesising evidence from clinical trials and real-world studies. We focus on drug discontinuation due to adverse events and the type and frequency of adverse events. This is the first review to analyse the effects of the long-term use of all anti-CGRP (receptor) mAbs, aiming to provide novel insights for clinical practice and future treatment strategies. Methods We systematically searched PubMed, Cochrane Library, and ClinicalTrials. gov for studies with ≥12 months of anti-CGRP (receptor) mAb use between January 2013 and April 2025. A random-effects meta-analysis of proportions (logit transformation, inverse variance weighting, restricted maximum likelihood) was performed to estimate pooled discontinuation and adverse event rates. Risk of bias was assessed using the ROBINS-I score. Results From a total of 1,499 records, 14 met the inclusion criteria and were eligible for data analysis. These 14 records corresponded to 11 individual studies with observational durations all exceeding 12 months. Seven studies investigated erenumab, two eptinezumab, and one each fremanezumab and galcanezumab. All studies were judged to have a severe risk of bias due to their underlying design. The overall pooled proportion of treatment discontinuation for any reason among patients receiving anti-CGRP (receptor) mAbs was 23%, whereas the pooled proportion of discontinuation specifically due to adverse events was substantially lower at 3% . Time-trend analysis showed that adverse event–related discontinuation remained low (<5%) beyond the first year, while overall adverse event incidence was high at baseline (>70%) but did not further increase with prolonged follow-up. Conclusion Evidence on long-term use of anti-CGRP (receptor) mAbs over 12 months remains limited, but our analysis indicates good tolerability with consistently low adverse event-related discontinuation, no emergent safety signals, and largely non-serious, stable adverse event profiles. However, heterogeneity and study-level bias warrant *Correspondence: Uwe Reuter [uwe. reuter@charite.de](uwe. reuter@charite.de) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. Hoehne e

FAQs

What was the study objective regarding anti-CGRP (receptor) mAbs?

To evaluate the long-term safety (≥12 months) of monoclonal antibodies targeting CGRP or its receptor in migraine prevention, using evidence from clinical trials and real-world studies.

How were long-term safety outcomes analyzed in this meta-analysis?

The review searched PubMed, Cochrane Library, and ClinicalTrials.gov for studies with ≥12 months of use, then used a random-effects meta-analysis to estimate pooled discontinuation and adverse-event rates. Risk of bias was assessed using ROBINS-I.

What were the key long-term discontinuation and adverse-event findings?

Overall pooled treatment discontinuation for any reason was 23%, while discontinuation due to adverse events was 3%. Adverse-event-related discontinuation stayed low (<5%) beyond the first year despite high baseline adverse event incidence (>70%).

What limitations does the conclusion highlight for long-term evidence?

Evidence over 12 months remains limited, with heterogeneity and study-level bias, supporting the need for longer-term clinical studies and continued real-world surveillance such as registries.

Sep 30, 2026

Uploaded by James