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October 2005

Effective Suppression of Cerebrospinal Fluid B Cells by Rituximab and Cyclophosphamide in Progressive Multiple Sclerosis—Reply

Author Affiliations

Copyright 2005 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2005

Arch Neurol. 2005;62(10):1642. doi:10.1001/archneur.62.10.1642-a

In reply

Included in this issue of the ARCHIVES is a case report describing a patient with relapsing-remitting MS who responded favorably to rituximab treatment alone1 and the preceding letter, which describes a patient with relapsing-remitting MS who responded favorably to rituximab combined with cyclophosphamide. In both instances, the authors also assessed CD19+ B cell frequencies in the peripheral blood and spinal fluid of their patients, as we had done in our previous report in the ARCHIVES.2 However, in contrast to our data, both of these cases demonstrated complete depletion of CD19+ CSF B cells in response to rituximab. Several factors may contribute to the apparent discordance with our results. First, the CSF was sampled during the first few courses of treatment, which represent much earlier samplings than what we had previously reported. We had hypothesized that B cell depletion in the CSF of patients with MS would require a longer period of exposure because it has been reported that rituximab concentrations in the CSF are roughly 10% of what can be achieved in the peripheral blood.3 However, the data presented in the preceding letter and the case report by Stüve et al1 suggest that CSF B cell depletion may occur at the same rate as in peripheral blood. Second, and perhaps even more importantly, the patients treated in these 2 cases had relapsing-remitting MS, rather than primary progressive MS, which further punctuates the possibility that these 2 distinct patient populations may respond to rituximab differently.