Serum Alpha and Beta-CGRP Levels in Chronic Migraine Patients Before and After Monoclonal Antibodies Against CGRP or its Receptor.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
27
03
2023
received:
19
12
2022
accepted:
01
04
2023
medline:
27
7
2023
pubmed:
12
4
2023
entrez:
11
4
2023
Statut:
ppublish
Résumé
The objective of this study was to analyze the evolution of alpha and beta-CGRP circulating levels throughout CGRP monoclonal antibodies (mAbs) treatment in patients with chronic migraine (CM). We recruited patients with CM beginning mAbs along with sex and age paired healthy controls (HCs). Blood was extracted before, 2 weeks (M0.5) and 3 months (M3) after the first dose of mAbs, always in free-migraine periods, and once for HCs. Alpha and beta-CGRP serum levels were measured using enzyme-linked immunosorbent assays (ELISAs) specific for each isoform. Baseline alpha-CGRP levels were significantly elevated in 103 patients with CM (median = 50.3, 95% confidence interval [CI] = 40.5-57.0 pg/ml) compared to 78 HCs (median = 37.5, 95% CI = 33.9-45.0 pg/ml; 95% CI of differences = 2.85-17.08 pg/ml) and significantly decreased (n = 96) over the course of mAb treatment (M0.5: median = 40.4, 95% CI = 35.6-48.2 pg/ml; and M3: median = 40.9, 95% CI = 36.3-45.9 pg/ml). Absolute decrease of alpha-CGRP throughout the treatment positively correlated with the decrease in MMDs. Negative modulation of alpha-CGRP significantly associated with positive scores at the Patient Global Impression of Change scale and with analgesic overuse reversal. Beta-CGRP did not differ at baseline between patients with CM (median = 4.2, 95% CI = 3.0-4.8 pg/ml) and HCs (median = 4.4, 95% CI = 3.4-5.6 pg/ml; -1.09 to 0.60) nor was modulated by mAb treatment (n = 96; M0.5: median = 4.5, 95% CI = 3.5-5.2 pg/ml; and M3: median = 4.6, 95% CI = 3.7-5.2 pg/ml). Treatment with mAbs, regardless of its target, is able to progressively normalize basally increased alpha-CGRP levels in CM and this effect correlates with efficacy measures, which supports a role of this neuropeptide as the first CM biomarker. ANN NEUROL 2023;94:285-294.
Substances chimiques
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Antibodies, Monoclonal
0
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
285-294Informations de copyright
© 2023 American Neurological Association.
Références
Vos T, Abajobir AA, Abbafati C, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the global burden of disease study 2016. Lancet 2017;390:1211-1259.
Goadsby PJ, Holland PR, Martins-Oliveira M, et al. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev 2017;97:553-622.
Edvinsson L. Calcitonin gene-related peptide (CGRP) is a key molecule released in acute migraine attacks-successful translation of basic science to clinical practice. J Intern Med 2022;292:575-586. https://doi.org/10.1111/joim.135.
Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990;28:183-187. https://doi.org/10.1002/ana.410280213.
Rodríguez-Osorio X, Sobrino T, Brea D, et al. Endothelial progenitor cells: a new key for endothelial dysfunction in migraine. Neurology 2012;79:474-479.
Alpuente A, Gallardo VJ, Asskour L, et al. Salivary CGRP can monitor the different migraine phases: CGRP (in)dependent attacks. Cephalalgia 2022;42:186-196.
Kamm K, Straube A, Ruscheweyh R. Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls. Cephalalgia 2019;39:1535-1543.
Van Dogen RM, Zielman R, Noga M, et al. Migraine biomarkers in cerebrospinal fluid: a systematic review and meta-analysis. Cephalalgia 2017;37:49-63.
Sarchielli P, Pini LA, Zanchin G, et al. Clinical-biochemical correlates of migraine attacks in rizatriptan responders and non-responders. Cephalalgia 2006;26:257-265.
Goadsby PJ, Edvinsson L. Human in vivo evidence for trigeminovascular activation in cluster headache neuropeptide changes and effects of acute attacks therapies. Brain 1994;117:427-434.
Cernuda-Morollón E, Ramón C, Martínez-Camblor P, et al. OnabotulinumtoxinA decreases interictal CGRP plasma levels in patients with chronic migraine. Pain 2015;156:820-824.
Domínguez C, Vieites-Prado A, Pérez-Mato M, et al. CGRP and PTX3 as predictors of efficacy of Onabotulinumtoxin type a in chronic migraine: an observational study. Headache 2018;58:78-87.
Cernuda-Morollón E, Larrosa D, Ramón C, et al. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology 2013;81:1191-1196.
Ashina M, Bendsten L, Jensen R, et al. Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks. Pain 2000;86:133-136.
Fusayasu E, Kowa H, Takeshma T, et al. Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods. Pain 2007;128:209-214.
Lassen LH, Haderslev PA, Jacobsen VB, et al. CGRP may play a causative role in migraine. Cephalalgia 2002;22:54-61.
Charles A, Pozo-Rosich P. Targeting calcitonin-gene related peptide: a new era in migraine therapy. Lancet 2019;394:1765-1774.
Yang CP, Zeng BY, Chang CM, et al. Comparative effectiveness and tolerability of the pharmacology of monoclonal antibodies targeting the calcitonin gene-related peptide and its receptor for the prevention of chronic migraine: a network meta-analysis of randomized controlled trials. Neurotherapeutics 2021;18:2639-2650.
Martelletti P, Edvinsson L, Ashina M. Shaping the future of migraine targeting calcitonin-gene-related-peptide with the disease-modifying migraine drugs (DMMDs). J Headache Pain 2019;20:19-21.
Russell FA, King R, Smillie SJ, et al. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev 2014;94:1099-1142.
Tvedskov JF, Lipka K, Ashina M, et al. No increase of calcitonin gene-related peptide in jugular blood during migraine. Ann Neurol 2005;58:561-568.
Lee MJ, Lee SY, Cho S, et al. Feasibility of serum CGRP measurement as a biomarker of chronic migraine: a critical reappraisal. J Headache Pain 2018;19:53. https://doi.org/10.1186/s10194-018-0883-x.
Messlinger K, Vogler B, Kuhn A, et al. CGRP measurements in human plasma - a methodological study. Cephalalgia 2021;41:1359-1373.
Edvinsson L, Ekman R, Goadsby PJ. Measurement of vasoactive neuropeptides in biological materials: problems and pitfalls from 30 years of experience and novel future approaches. Cephalalgia 2010;30:761-766.
Kamm K. CGRP and migraine: what have we learned from measuring CGRP in migraine patients so far? Front Neurol 2022;13:13. https://doi.org/10.3389/fneur.2022.930383.
Headache classification Committee of the International Headache Society (IHS). The international classification of headache disorders. Cephalalgia 2018;38:1-211.
Scott W, McCracken LM. Patients' impression of change following treatment for chronic pain: global, specific, a single dimension, or many? J Pain 2015;16:518-526.
Su M, Yu S. Chronic migraine: a process of dysmodulation and sensitization. Mol Pain 2018;14:14. https://doi.org/10.1177/1744806918767697.
Riesco N, Cernuda-Morollón E, Pascual J. Neuropeptides as a marker for chronic migraine. Curr Pain Headache Rep 2017;21:18. https://doi.org/10.1007/s11916-017-0618-8.
Ramón C, Cernuda-Morollón E, Pascual J. Calcitonin gene-related peptide in peripheral blood as a biomarker for migraine. Curr Opin Neurol 2017;30:281-286.
Pozo-Rosich P, Coppola G, Pascual J, Schwedt TJ. How does the brain change in chronic migraine? Developing disease biomarkers. Cephalalgia 2021;41:613-630.
de Vries LS, Garrelds IM, Danser AHJ, et al. Serum CGRP in migraine patients using erenumab as preventive treatment. J Headache Pain 2022;23:120. https://doi.org/10.1186/s10194-022-01483-z.
Alpuente A, Gallardo VJ, Asskour MLT, et al. Salivary CGRP and erenumab treatment response: towards precision medicine in migraine. Ann Neurol 2022;92:846-859.
Hoffmann J, Wecker S, Neeb L, et al. Primary trigeminal afferents are the main source for stimulus-induce CGRP into jugular vein blood and CSF. Cephalalgia 2012;32:659-667.
Falkenberg K, Bjerg HR, Olesen J. Two-hour CGRP infusion causes gastrointestinal hyperactivity: possible relevance for CGRP antibody treatment. Headache 2020;60:929-937.
Holzer P, Holzer-Petsche U. Constipation caused by anti-calcitonin gene-related peptide migraine therapeutics explained by antagonism of calcitonin gene-related peptide's motor-stimulating and prosecretory function in the intestine. Front Physiol 2022;12:1-17. https://doi.org/10.3389/fphys.2021.820006.