Long-Term Consequences of High Titer Neutralizing Antibodies to Interferon-β in Multiple Sclerosis.
annual relapse rate
immunogenicity
interferon-β
multiple sclerosis
neutralizing antibodies
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
16
07
2020
accepted:
07
09
2020
entrez:
12
11
2020
pubmed:
13
11
2020
medline:
16
6
2021
Statut:
epublish
Résumé
Neutralizing anti-drug antibodies (NAbs) to interferon beta (IFNβ) develop in up to 47% of multiple sclerosis (MS) treated patients inhibiting treatment effect of IFNβ. However, the long-term effect of NAbs remain unknown. To investigate the long-term consequences of high titer NAbs to IFNβ on disease activity and progression in MS patients. An observational study including data from all IFNβ treated relapsing remitting MS patients with sufficient NAb test results from the Swedish MS registry. Patients were classified into either confirmed 'high titer' or 'persistent negative' groups and analyzed for differences in disease activity and progression over time. A total of 197 high-titer and 2907 persistent negative patients with 19969.6 follow up years of data were included. High titer NAbs were associated with a higher degree of disease activity at baseline. However, even when accounting for this, the presence of high titer NAbs were also associated with higher disease activity during IFNβ treatment. This persisted even after the next DMT start, suggesting that earlier high titers may partially reduce the effect of later treatments. No difference was found in confirmed disability progression. High titer NAbs to IFNβ are associated with higher disease activity, persisting even after IFNβ discontinuation or switch. These results support use of highly efficient treatment earlier in patients with active disease, to avoid these complications.
Sections du résumé
Background
Neutralizing anti-drug antibodies (NAbs) to interferon beta (IFNβ) develop in up to 47% of multiple sclerosis (MS) treated patients inhibiting treatment effect of IFNβ. However, the long-term effect of NAbs remain unknown.
Objective
To investigate the long-term consequences of high titer NAbs to IFNβ on disease activity and progression in MS patients.
Methods
An observational study including data from all IFNβ treated relapsing remitting MS patients with sufficient NAb test results from the Swedish MS registry. Patients were classified into either confirmed 'high titer' or 'persistent negative' groups and analyzed for differences in disease activity and progression over time.
Results
A total of 197 high-titer and 2907 persistent negative patients with 19969.6 follow up years of data were included. High titer NAbs were associated with a higher degree of disease activity at baseline. However, even when accounting for this, the presence of high titer NAbs were also associated with higher disease activity during IFNβ treatment. This persisted even after the next DMT start, suggesting that earlier high titers may partially reduce the effect of later treatments. No difference was found in confirmed disability progression.
Conclusion
High titer NAbs to IFNβ are associated with higher disease activity, persisting even after IFNβ discontinuation or switch. These results support use of highly efficient treatment earlier in patients with active disease, to avoid these complications.
Identifiants
pubmed: 33178215
doi: 10.3389/fimmu.2020.583560
pmc: PMC7593513
doi:
Substances chimiques
Antibodies, Neutralizing
0
Immunologic Factors
0
Interferon-beta
77238-31-4
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
583560Informations de copyright
Copyright © 2020 Dunn, Fogdell-Hahn, Hillert and Spelman.
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