" The Lancet, Volume 379, Issue 9822, Pages 1196 - 1197, 31 March 2012 <Previous Article|Next Article>doi:10.1016/S0140-6736(12)60508-XCite or Link Using DOIOcrelizumab in multiple sclerosis: risks and benefits
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 ... X/fulltext