Ocrelizumab is a humanized monoclonal anti-CD20 antibody constructed with recombinant DNA techniques and designed to selectively target CD20 B cells. (Rituxan is a "chimeric murine-human monoclonal antibody".) In vitro characterization of ocrelizumab demonstrated enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and reduced complement-dependent cytotoxicity (CDC) as compared with rituximab. Ocrelizumab binds to a different, but overlapping, epitope of the extracellular domain of CD20 as compared with rituximab.
http://www.reumagalicia.com/addonsdata/ ... iculo9.pdf
Pesho wrote:Got my second infusion today. Was feeling a bit hot at moments, also my blood pressure went from 110/70 to 120/80 at the end of the infusion, but still normal for a man my size. After that went for a four hour walk shopping stuff. Felt my legs a bit stiff after 3+ hours on bed, but things got better with walking . So, no side effects to Rebif, no side effects to Ocrelizumab. Still on a low dose of Rebif, will see how it goes in 2 weeks when I get to Rebif 44, for now I only have red spots on the injection sites, and not from all shots.
Any news so far ?
Abhijit Chaudhuri aI have several concerns about the clinical trial by Ludwig Kappos and colleagues (Nov 19, p 1779)1 of the monoclonal antibody ocrelizumab in relapsing-remitting multiple sclerosis.
First, I disagree that ocrelizumab has a benign safety profile. The death of a patient in the high-dose group was the direct effect of a drug that has been widely associated with a serious risk of infection in other studies.2 The natural history of multiple sclerosis3 suggests that the ultimate cause of death in these patients is infection; immunosuppression could potentially accelerate the process.
Second, the outcome data did not show a dose-response relation. This finding, and the time course of treatment response, make it highly unlikely that escalation of B-cell depletion by immunotherapy alters the natural course of multiple sclerosis.
Third, the putative benefit from immunotherapies in multiple sclerosis is largely driven by MRI markers that do not correlate reliably with long-term disability. Kappos and colleagues did not provide scores on the expanded disability status scale at weeks 24 and 48, so it is not possible to make a comparison with baseline scores. Of interest is that there was no difference in serious relapse of multiple sclerosis between the treatment groups.
One must use extreme caution in accepting the published trial data as proof of the concept of B-cell-driven pathogenesis in multiple sclerosis. Indeed, most authors of this paper were also involved with the clinical trial of B-cell-targeted treatment with atacicept that was terminated by the sponsor because of serious worsening of disease in the treated groups (ClinicalTrials.govNCT00642902).
The lessons from the clinical trial of natalizumab4 seem to have been forgotten too quickly: nearly a quarter of more than 200 patients with natalizumab-induced progressive multifocal leukoencephalopathy are dead and most of the rest are severely disabled by the drug rather then their disease. Quo vadis multiple sclerosis?
I declare that I have no conflicts of interest. "
http://www.thelancet.com/journals/lance ... S0140-6736(12%2960508-X/fulltext
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