Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials.
Adult
Antibodies, Neutralizing
/ immunology
Female
Genome-Wide Association Study
HLA-DRB1 Chains
/ genetics
Humans
Immunologic Factors
/ administration & dosage
Interferon beta-1b
/ administration & dosage
Male
Middle Aged
Multiple Sclerosis
/ drug therapy
Multiple Sclerosis, Relapsing-Remitting
/ drug therapy
Polymorphism, Single Nucleotide
Prospective Studies
HLA-DRB1
Multiple sclerosis
anti-drug antibodies
genetic variation
genome-wide association study
interferon beta
Journal
Multiple sclerosis (Houndmills, Basingstoke, England)
ISSN: 1477-0970
Titre abrégé: Mult Scler
Pays: England
ID NLM: 9509185
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
pubmed:
10
3
2018
medline:
10
1
2020
entrez:
10
3
2018
Statut:
ppublish
Résumé
Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. To validate the proposed genetic markers and to identify new markers. Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10 The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies.
Sections du résumé
BACKGROUND
Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β.
OBJECTIVE
To validate the proposed genetic markers and to identify new markers.
METHODS
Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon
RESULTS
We confirmed an increased risk for carriers of HLA-DRB1*04:01 (odds ratio (OR) = 3.3, p = 6.9 × 10
CONCLUSION
The contribution of HLA alleles and HLA-associated single-nucleotide polymorphisms (SNPs) to the development and titer of antibodies against interferon β was confirmed in the combined analysis of two multi-national, multi-center studies.
Identifiants
pubmed: 29521573
doi: 10.1177/1352458518763089
doi:
Substances chimiques
Antibodies, Neutralizing
0
HLA-DRB1 Chains
0
HLA-DRB1*04:01 antigen
0
HLA-DRB1*07 antigen
0
Immunologic Factors
0
Interferon beta-1b
145155-23-3
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM