Back to Search
Start Over
The effects of intrathecal rituximab on biomarkers in multiple sclerosis.
- Source :
-
Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2016 Mar; Vol. 6, pp. 49-53. Date of Electronic Publication: 2016 Jan 19. - Publication Year :
- 2016
-
Abstract
- Objectives: Clinical trials of IV-rituximab have proved successful. It is unclear whether intrathecal (IT)-rituximab is more efficacious at lower doses. We examine its effects on B-cell biomarkers.<br />Methods: MS patients received IT-rituximab at 3 time-points. CSF and serum samples were obtained at up to 5 time-points (days 0, 7, 14, 56 and 112). Serum and CSF BAFF and CXCL13, and CSF kappa and lambda free light chains (FLC) were measured. Flow cytometry was performed, examining effects on lymphocytes, CD3-19+ and CD3-20+ cells.<br />Results: CSF BAFF fell following rituximab (p=0.0091 absolute values, p=0.0284 change from baseline) whilst serum BAFF increased across time-points 1-4 (p=0.0005 absolute values, p=0.0017 change from baseline). There were significant reductions in CD20+ and CD19+ cells in blood from baseline (p<0.0001) but not in CSF. CSF kappa FLC levels significantly increased (p=0.0480).<br />Conclusions: BAFF levels fall in CSF but increase in serum following IT-rituximab. Rituximab appears to act peripherally with dramatic decreases in peripheral CD20+ and CD19+ cells. It is likely that CSF B-cell counts were too low to enable differences to be seen. The rapid reduction in B-cells suggests rituximab has immediate effects. The profound depletion of B-cells, despite low doses of rituximab, underlines rituximab's efficacy.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Adult
Antigens, CD19 metabolism
Antigens, CD20 metabolism
B-Cell Activating Factor blood
B-Cell Activating Factor cerebrospinal fluid
Biomarkers blood
Biomarkers cerebrospinal fluid
Chemokine CXCL13 blood
Chemokine CXCL13 cerebrospinal fluid
Dose-Response Relationship, Drug
Female
Humans
Immunoglobulin kappa-Chains cerebrospinal fluid
Immunoglobulin lambda-Chains cerebrospinal fluid
Immunologic Factors blood
Immunologic Factors cerebrospinal fluid
Injections, Spinal
Lymphocytes drug effects
Lymphocytes metabolism
Male
Middle Aged
Multiple Sclerosis, Chronic Progressive blood
Multiple Sclerosis, Chronic Progressive cerebrospinal fluid
Multiple Sclerosis, Relapsing-Remitting blood
Multiple Sclerosis, Relapsing-Remitting cerebrospinal fluid
Rituximab blood
Rituximab cerebrospinal fluid
Treatment Outcome
Immunologic Factors administration & dosage
Multiple Sclerosis, Chronic Progressive drug therapy
Multiple Sclerosis, Relapsing-Remitting drug therapy
Rituximab administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 2211-0356
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Multiple sclerosis and related disorders
- Publication Type :
- Academic Journal
- Accession number :
- 27063622
- Full Text :
- https://doi.org/10.1016/j.msard.2016.01.001