MS and Rituximab

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Rituximab is a monoclonal antibody binding to [the CD20 antigen of] mature B-lymphocytes, which are subsequently killed by the body’s natural defence. Stem cells in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return within some months.

       Cross et al. [[1]] found that Rituximab depleted B cells from CSF at 24 weeks after initial treatment, and this B cell depletion was associated with a reduction in CSF T cells as well. The drug was originally registered for the treatment of leukaemia and rheumatoid arthritis and has now been shown effective in ameliorating MS.

       In February 2008, Hauser et al. [[2]] published a study using 1000 mg of intravenous rituximab for patients with RR-MS on days 1 and 15 and then nothing else for almost a year, finding it effective for at least 48 weeks.

       Bar-Or et al [[3]] used an intensified dosing scheme, notably without placebo-victims (a positive ethical trend?). They used 4 infusions of rituximab [1000 mg] at weeks 0, 2, 24 and 26 and followed for a total of 72 weeks. Over the 72 weeks, 21 patients remained relapse free. Four patients reported one and one patient two relapses. The authors con­cluded that B cells may play an important role in the ongoing MS immuno­pathogenesis.

       With the knowledge that also patients with SP-MS may profit from this drug (casuistic experience, no study yet available?), Monson et al. [[4]] tried it in patients with PP-MS, for whom no other tested therapy is available. Unfortunately, no considerable effect was found here (statistically significant above placebo), but a final evaluation was pending at the time of this review. “There was some evidence of biologic activity” may awake some hope.

[1] AH Cross, JL Stark, J Lauber, MJ Ramsbottom, J-A Lyons. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2006:180: 63–70.

[2] Hauser SL et al. B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis. NEJM 2008 358:676-688.

[3] A Bar-Or et al. Rituximab in Relapsing-Remitting Multiple Sclerosis: A 72-Week, Open-Label, Phase I Trial. Ann Neurol 2008;63:395–400.

[4] NL Monson, PD Cravens, EM Frohman, K Hawker, MK Racke. Effect of Rituximab on the peripheral blood and cerebrospinal fluid B cells in patients with primary progressive multiple sclerosis. Arch Neurol 2005;62:258-264.