Clinic and genetic predictors in response to erenumab.


Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
04 2022
Historique:
revised: 20 11 2021
received: 15 07 2021
accepted: 21 12 2021
pubmed: 30 12 2021
medline: 5 4 2022
entrez: 29 12 2021
Statut: ppublish

Résumé

Erenumab (ERE) is the first anticalcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE. Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio-demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine-related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test-6), and use of abortive medications, during 3 months before and after ERE start were collected. Real-time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50-RESP) and 75% responder patients (75-RESP). At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50-RESP, and 30/110 (27.3%) were 75-RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008-1.120], p = 0.024), number of failed preventive medications (0.753 [0.600-0.946], p = 0.015), and MIDAS score (1.011 [1.002-1.020], p = 0.017) were associated with 75-RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75-RESP (per G allele OR [95% CI]: 0.53 [0.29-0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28-1.10], p = 0.09]). In this real-word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.

Sections du résumé

BACKGROUND AND PURPOSE
Erenumab (ERE) is the first anticalcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE.
METHODS
Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio-demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine-related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test-6), and use of abortive medications, during 3 months before and after ERE start were collected. Real-time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50-RESP) and 75% responder patients (75-RESP).
RESULTS
At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50-RESP, and 30/110 (27.3%) were 75-RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008-1.120], p = 0.024), number of failed preventive medications (0.753 [0.600-0.946], p = 0.015), and MIDAS score (1.011 [1.002-1.020], p = 0.017) were associated with 75-RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75-RESP (per G allele OR [95% CI]: 0.53 [0.29-0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28-1.10], p = 0.09]).
CONCLUSIONS
In this real-word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.

Identifiants

pubmed: 34965002
doi: 10.1111/ene.15236
pmc: PMC9306465
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
erenumab I5I8VB78VT

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1209-1217

Informations de copyright

© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

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Auteurs

Chiara Zecca (C)

Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.

Sarah Cargnin (S)

Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale "A. Avogadro", Novara, Italy.

Christoph Schankin (C)

Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Nadia Mariagrazia Giannantoni (NM)

Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.

Michele Viana (M)

Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.

Isabella Maraffi (I)

Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.

Gianna Carla Riccitelli (GC)

Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.

Shairin Sihabdeen (S)

Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.

Salvatore Terrazzino (S)

Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale "A. Avogadro", Novara, Italy.

Claudio Gobbi (C)

Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.
Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.

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Classifications MeSH