Journal article
Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies.
- Dunn N Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
- Juto A Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
- Ryner M Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
- Manouchehrinia A Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
- Piccoli L Immune Regulation Laboratory, Institute for Research in Biomedicine, Bellinzona, Switzerland.
- Fink K Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
- Piehl F Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
- Fogdell-Hahn A Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
- 2017-08-02
Published in:
- Multiple sclerosis (Houndmills, Basingstoke, England). - 2018
Antidrug antibodies
B-cell depletion
MAb
anti-CD20
immunogenicity
multiple sclerosis
rituximab
Adult
Antibodies, Anti-Idiotypic
B-Lymphocytes
Cross-Sectional Studies
Female
Humans
Immunologic Factors
Lymphocyte Count
Male
Middle Aged
Multiple Sclerosis
Rituximab
English
BACKGROUND
Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown.
OBJECTIVE
To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients.
METHODS
Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion. ADAs were detected using an in-house-validated electrochemiluminescent immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient demographics and clinical outcomes were retrieved from the Swedish MS Registry and patient records.
RESULTS
ADAs were detected in 37% of relapsing-remitting MS and 26% in progressive forms of MS. Presence of ADAs decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADAs and incomplete B-cell depletion, but not with infusion/adverse reactions or clinical outcomes at the group level. Only five patients terminated rituximab during follow-up, four of which were ADA positive.
CONCLUSION
Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.
Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown.
OBJECTIVE
To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients.
METHODS
Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion. ADAs were detected using an in-house-validated electrochemiluminescent immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient demographics and clinical outcomes were retrieved from the Swedish MS Registry and patient records.
RESULTS
ADAs were detected in 37% of relapsing-remitting MS and 26% in progressive forms of MS. Presence of ADAs decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADAs and incomplete B-cell depletion, but not with infusion/adverse reactions or clinical outcomes at the group level. Only five patients terminated rituximab during follow-up, four of which were ADA positive.
CONCLUSION
Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1177/1352458517720044
- PMID 28762877
- Persistent URL
- https://sonar.ch/global/documents/92981
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