1. The effects of intrathecal rituximab on biomarkers in multiple sclerosis.
- Author
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Topping J, Dobson R, Lapin S, Maslyanskiy A, Kropshofer H, Leppert D, Giovannoni G, and Evdoshenko E
- 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
- 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., 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., 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)., 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., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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