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Immunogenicity of biologic therapies for migraine: a review of current evidence
BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been shown to be effective in migraine prevention. Eptinezumab, erenumab, fremanezumab, and galcanezumb have shown efficacy in clinical trials along with favorable safety and tolerability profi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Milan
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791637/ https://www.ncbi.nlm.nih.gov/pubmed/33413094 http://dx.doi.org/10.1186/s10194-020-01211-5 |
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author | Cohen, Joshua M. Ning, Xiaoping Kessler, Yoel Rasamoelisolo, Michele Campos, Verena Ramirez Seminerio, Michael J. Krasenbaum, Lynda J. Shen, Honglue Stratton, Jennifer |
author_facet | Cohen, Joshua M. Ning, Xiaoping Kessler, Yoel Rasamoelisolo, Michele Campos, Verena Ramirez Seminerio, Michael J. Krasenbaum, Lynda J. Shen, Honglue Stratton, Jennifer |
author_sort | Cohen, Joshua M. |
collection | PubMed |
description | BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been shown to be effective in migraine prevention. Eptinezumab, erenumab, fremanezumab, and galcanezumb have shown efficacy in clinical trials along with favorable safety and tolerability profiles. Although erenumab is a human mAb and the others have been humanized to varying degrees, they all have the capacity to provoke immune reactions. The present review article aims to discuss the current relationship between mAbs targeting the CGRP pathway (CGRP mAbs) and immunogenicity and their potential clinical implications. FINDINGS: The incidence of patients developing anti-drug antibodies (ADAs), their titer, and clinical significance are highly variable and depend on a variety of different drug and patient factors. Neutralizing ADAs (NAbs) bind to and inhibit or reduce the pharmacologic activity of the biologic drug molecule, whereas non-neutralizing antibodies (Non-NAbs) bind to the biologic drug molecule without affecting pharmacologic activity in an in vitro test, although pharmacokinetics and drug clearance may be affected. A direct comparison of immunogenicity data across clinical trials with different biologics is not possible due to a lack of standardized assays. Several phase 2, phase 3, and long-term studies evaluating CGRP mAbs for migraine prevention have reported immunogenicity data (5 studies each for eptinezumab, erenumab, fremanezumab, and galcanezumab). Across these studies, prevalence of ADAs varied, ranging from < 1% to ~ 18%. Neutralizing ADAs were slightly less common, with a prevalence ranging from 0 to 12%. Adverse events related to ADA formation were rare. CONCLUSIONS: As more CGRP mAb studies are conducted and more long-term follow-up data become available, evidence is increasing that immunogenicity rates of biologic therapies for migraine are low, and adverse events related to ADAs are rare. Taken together, these results add to the growing body of evidence for the safety and tolerability of this class of migraine medications. |
format | Online Article Text |
id | pubmed-7791637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Milan |
record_format | MEDLINE/PubMed |
spelling | pubmed-77916372021-01-11 Immunogenicity of biologic therapies for migraine: a review of current evidence Cohen, Joshua M. Ning, Xiaoping Kessler, Yoel Rasamoelisolo, Michele Campos, Verena Ramirez Seminerio, Michael J. Krasenbaum, Lynda J. Shen, Honglue Stratton, Jennifer J Headache Pain Review Article BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been shown to be effective in migraine prevention. Eptinezumab, erenumab, fremanezumab, and galcanezumb have shown efficacy in clinical trials along with favorable safety and tolerability profiles. Although erenumab is a human mAb and the others have been humanized to varying degrees, they all have the capacity to provoke immune reactions. The present review article aims to discuss the current relationship between mAbs targeting the CGRP pathway (CGRP mAbs) and immunogenicity and their potential clinical implications. FINDINGS: The incidence of patients developing anti-drug antibodies (ADAs), their titer, and clinical significance are highly variable and depend on a variety of different drug and patient factors. Neutralizing ADAs (NAbs) bind to and inhibit or reduce the pharmacologic activity of the biologic drug molecule, whereas non-neutralizing antibodies (Non-NAbs) bind to the biologic drug molecule without affecting pharmacologic activity in an in vitro test, although pharmacokinetics and drug clearance may be affected. A direct comparison of immunogenicity data across clinical trials with different biologics is not possible due to a lack of standardized assays. Several phase 2, phase 3, and long-term studies evaluating CGRP mAbs for migraine prevention have reported immunogenicity data (5 studies each for eptinezumab, erenumab, fremanezumab, and galcanezumab). Across these studies, prevalence of ADAs varied, ranging from < 1% to ~ 18%. Neutralizing ADAs were slightly less common, with a prevalence ranging from 0 to 12%. Adverse events related to ADA formation were rare. CONCLUSIONS: As more CGRP mAb studies are conducted and more long-term follow-up data become available, evidence is increasing that immunogenicity rates of biologic therapies for migraine are low, and adverse events related to ADAs are rare. Taken together, these results add to the growing body of evidence for the safety and tolerability of this class of migraine medications. Springer Milan 2021-01-07 /pmc/articles/PMC7791637/ /pubmed/33413094 http://dx.doi.org/10.1186/s10194-020-01211-5 Text en © The Author(s) 2021 Open AccessThis 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/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Article Cohen, Joshua M. Ning, Xiaoping Kessler, Yoel Rasamoelisolo, Michele Campos, Verena Ramirez Seminerio, Michael J. Krasenbaum, Lynda J. Shen, Honglue Stratton, Jennifer Immunogenicity of biologic therapies for migraine: a review of current evidence |
title | Immunogenicity of biologic therapies for migraine: a review of current evidence |
title_full | Immunogenicity of biologic therapies for migraine: a review of current evidence |
title_fullStr | Immunogenicity of biologic therapies for migraine: a review of current evidence |
title_full_unstemmed | Immunogenicity of biologic therapies for migraine: a review of current evidence |
title_short | Immunogenicity of biologic therapies for migraine: a review of current evidence |
title_sort | immunogenicity of biologic therapies for migraine: a review of current evidence |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791637/ https://www.ncbi.nlm.nih.gov/pubmed/33413094 http://dx.doi.org/10.1186/s10194-020-01211-5 |
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