B cells and disease activity and anti-drug responses prior to and following alemtuzumab infusion for multiple sclerosis

B cells and disease activity and anti-drug responses prior to and following alemtuzumab infusion for multiple sclerosis

Multiple sclerosis is an autoimmune disease of the central nervous system. Alemtuzumab is a lymphocyte (type of white blood cells) depleting monoclonal antibody that is effective at controlling relapsing multiple sclerosis. Although focus has been on T helper cells (A white blood cell subtype educated in the thymus) as mediators for disease control we have discovered that memory B cells (another type of white blood cell from cells produced in the Bone marrow which has been activated and can differentiate to form cells capable of producing antibodies) may be major target for disease control by alemtuzumab and all other multiple sclerosis drugs. Importantly their slow repopulation after depletion means it is possible to control disease for years from a short treatment cycle. It is believed that monitoring depletion and repopulation of memory B cells can predict disease breakthrough and may be used to provide an indication for re-treatment to maintain remission, as occurs with some lymphocyte subset-depeleting antibodies. However, the action of alemtuzumab can be limited by the development of anti-drug antibodies. We hypothesised that anti-drug antibodies that block drug activity may predict treatment failure in some individuals. We made assays to demonstrate this and it seems that some people do indeed fail treatment and that it may be able to predict this from the levels of anti-drug antibodies. The clinical studies monitor people for five years after treatment with alemtuzumab and repeated check white blood cell levels, anti-drug antibody responses and disease activity. This has been done in over 800 people with multiple sclerosis and analysing this data in a novel way can address where memory B cells levels increase before disease breakthrough and also may provide us with anti-drug antibody levels that can predict lack of lymphocyte depletion, which is often associated with subsequent treatment failure. This will help us to make use of alemtuzumab safer as it can may help us to predict treatment failure before it happens allow us to swtich treatment in the few individuals that fail this very effective treatment

[{ "PostingID": 19693, "Title": "SANOFI-CAMMS323
(CARE-MS I)", "Description": "A Phase 3 Randomized, Rater-Blinded Study Comparing Two Annual Cycles of Intravenous Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif®) in Treatment-Naïve Patients With Relapsing-Remitting Multiple Sclerosis" },{ "PostingID": 19694, "Title": "SANOFI-CAMMS32400507
(CAMMS324/ CARE-MS II)", "Description": "A Phase 3, Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta 1a (Rebif®) in Patients With Relapsing Remitting Multiple Sclerosis Who Have Relapsed On Therapy" }]