Rituximab in relapsing-remitting multiple sclerosis: A 72-week, open-label, phase I trial†
Corresponding Author
Amit Bar-Or MD
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
Neuroimmunology Unit and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, 3801 University, Room 111, Montreal, QC H3A 2B4, CanadaSearch for more papers by this authorPeter A. J. Calabresi MD
Department of Neurology, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorDouglas Arnold MD
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
NeuroRx Research, Montreal, Quebec, Canada
Search for more papers by this authorClyde Markowitz MD
Hospital of the University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorEmmanuelle Waubant MD
Department of Neurology, University of California at San Francisco, CA
Search for more papers by this authorRobert J. Fox MD
Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH
Search for more papers by this authorNeena Sarkar PhD
Genentech, Incorporated, South San Francisco, CA
Search for more papers by this authorSunil Agarwal MD
Genentech, Incorporated, South San Francisco, CA
Search for more papers by this authorCraig H. Smith MD
Genentech, Incorporated, South San Francisco, CA
Search for more papers by this authorCorresponding Author
Amit Bar-Or MD
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
Neuroimmunology Unit and Experimental Therapeutics Program, Montreal Neurological Institute, McGill University, 3801 University, Room 111, Montreal, QC H3A 2B4, CanadaSearch for more papers by this authorPeter A. J. Calabresi MD
Department of Neurology, Johns Hopkins Hospital, Baltimore, MD
Search for more papers by this authorDouglas Arnold MD
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
NeuroRx Research, Montreal, Quebec, Canada
Search for more papers by this authorClyde Markowitz MD
Hospital of the University of Pennsylvania, Philadelphia, PA
Search for more papers by this authorEmmanuelle Waubant MD
Department of Neurology, University of California at San Francisco, CA
Search for more papers by this authorRobert J. Fox MD
Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH
Search for more papers by this authorNeena Sarkar PhD
Genentech, Incorporated, South San Francisco, CA
Search for more papers by this authorSunil Agarwal MD
Genentech, Incorporated, South San Francisco, CA
Search for more papers by this authorCraig H. Smith MD
Genentech, Incorporated, South San Francisco, CA
Search for more papers by this authorThis article has been corrected since its original publication. Please see Annals of Neurology 2008;63;803 for further details.
Abstract
We evaluated the safety, tolerability, pharmacodynamics, and activity of B-cell depletion with rituximab in patients with relapsing-remitting multiple sclerosis, receiving two courses of rituximab 6 months apart, and followed for a total of 72 weeks. No serious adverse events were noted; events were limited to mild-to-moderate infusion-associated events, which tended to decrease with subsequent infusions. Infections were also mild or moderate, and none led to withdrawal. Fewer new gadolinium-enhancing or T2 lesions were seen starting from week 4 and through week 72. An apparent reduction in relapses was also observed over the 72 weeks compared with the year before therapy. Ann Neurol 2008
Supporting Information
This article includes supplementary materials available via the Internet at http://www.interscience.wiley.com/jpages/0364-5134/suppmat
| Filename | Description |
|---|---|
| ana21363-supplementaryfigure.eps1.3 MB | Supplementary Figure. Median Counts per mm 3for total CD19+ B Cells (A), CD19+CD27+ Memory B Cells (B), and CD19+CD27- Naive B Cells (C). As expected from its mechanism of action, treatment with rituximab led to rapid depletion of peripheral B cells (measured by CD19 expression), which was near-complete (99.8%) by Week 2, and sustained through Week 48, with reconstitution to mean 34.5% of baseline by Week 72. The majority of reconstituting cells were CD19+CD27- naive B cells (mean 51% of baseline) rather than CD19+CD27+ memory B cells (mean 14% of baseline). |
| ana21363-SupplementaryTable1.pdf98.5 KB | Supplementary Table 1: Patient Baseline Characteristics at Entry (ITT Population). |
| ana21363-SupplementaryTable2.pdf48.7 KB | Supplementary Table 2. Adverse Events, N (%). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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