The effects of intrathecal rituximab on biomarkers in multiple sclerosis. / Topping, Joanne; Dobson, Ruth; Lapin, Sergey; Maslyanskiy, Alexey; Kropshofer, Harald; Leppert, David; Giovannoni, Gavin; Evdoshenko, Evgeniy.
In: Multiple Sclerosis and Related Disorders, Vol. 6, 01.03.2016, p. 49-53.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - The effects of intrathecal rituximab on biomarkers in multiple sclerosis
AU - Topping, Joanne
AU - Dobson, Ruth
AU - Lapin, Sergey
AU - Maslyanskiy, Alexey
AU - Kropshofer, Harald
AU - Leppert, David
AU - Giovannoni, Gavin
AU - Evdoshenko, Evgeniy
N1 - Publisher Copyright: © 2016 Published by Elsevier B.V.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - B-cells
KW - BAFF
KW - biomarkers
KW - CD19+
KW - CD20+
KW - Intrathecal rituximab
UR - http://www.scopus.com/inward/record.url?scp=84962488263&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2016.01.001
DO - 10.1016/j.msard.2016.01.001
M3 - Article
C2 - 27063622
AN - SCOPUS:84962488263
VL - 6
SP - 49
EP - 53
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
ER -
ID: 93111519