Ocrelizumab Targets B Cells And Reduces MS-Related Brain Lesions

Stuart SchlossmanMS Research Study and Reports, Multiple Sclerosis, Oral MS Medications

02 Nov 2011   Multiple sclerosis (MS) is a chronic and disabling disease, in which a person’s central nervous system (brain, spinal cord and optic nerves) is attacked by their immune system, causing inflammation and onsets of neurological dysfunction, and over time results in progressive disability. Inflammations can be identified as inflammatory lesions by performing MRI scans on the brain and due to the progressiveness of the disease patients suffer relapses in neurological dysfunctions. More common in women and Caucasians, MS generally manifests itself in young adulthood. According to an article published Online First in The Lancet a phase 2 randomized, open label, placebo-controlled trial demonstrated the new monoclonal antibody ocrelizumab successfully targets B cells, immune cells implicated in multiple sclerosis, and rapidly reduces disease-related, inflammatory brain lesions and clinical attacks. Ocrelizumab is a recombinant, humanized, monoclonal antibody, developed to selectively target CD20-positive B cells. (CD20 is a cell surface protein expressed on select B cells). T cells of the body’s immune system govern cell-mediated immune responses, such as activation of natural killer cells, whereas B cells govern antibody-related or ‘humoral’ immune response. Scientists used to believe the inflammation in MS was exclusively controlled by T cells, however, according to recent evidence, B cells are thought to drive the abnormal immune response in these patients. The author Professor Ludwig Kappos of the Departments of Neurology and Biomedicine at the University Hospital Basel in Switzerland and his team evaluated the efficacy and safety of two dose regimens of ocrelizumab in patients with relapsing-remitting multiple sclerosis and compared ocrelizumab with the standard MS treatment of once-a-week administration of interferon beta-1a, which is thought to reduce inflammation. The international multi-center study (79 centers in 20 countries) was conducted on 218 patients aged 18-55 years with relapsing-remitting multiple sclerosis. The participants were split into 4 different groups. The first group consisted of 54 patients receiving placebo, whilst the second group and third group each containing 55 participants received either a low-dose (600 mg) or a high-dose (2000 mg) of ocrelizumab, and 54 patients in the fourth group received the standard once-weekly treatment of intramuscular interferon beta-1a (30μg). The dose ratio was determined as 1:1:1:1. At week 24, the first (placebo), second (ocrelizumab 600mg) and fourth (beta-1a) group received 600 mg of ocrelizumab, whilst the dose of the third, the high-dose group, was reduced to 1000 mg of ocrelizumab. The study’s primary endpoint was determined as the total number of active (contrast enhancing) lesions per group that were established with MRI scans of the brain at 12, 16, 20, and 24 weeks. Researchers discovered at week 24 that the number of active lesions was 89% lower in the 600 mg ocrelizumab low-dose group and 96% lower in the 2000 mg high-dose group compared with the placebo group. The exploratory evaluation demonstrated that both ocrelizumab groups performed better compared with the interferon beta-1a group by equal margins, however, further confirmation is required in future studies. 
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