Friday, 28 April 2017

AAN2017. B cells and Disease Activity


348  Relationship between MRI Lesion Count and B Cell Count Reduction under Ofatumumab Treatment  M. Savelieva (Novartis Pharma AG, Basel, Switzerland), J. Kahn (Novartis Pharma AG, Basel, Switzerland), E. Wallstroem (Novartis Pharma AG, Basel, Switzerland), D. Leppert (Novartis Pharma AG, Basel, Switzerland). 

Objective: To characterize the relationship of B cell depletion with gadolinium enhanced (Gd+ ) magnetic resonance imaging lesion counts under ofatumumab treatment. 
Background: Ofatumumab is a fully human anti-CD20 monoclonal antibody that depletes circulating peripheral B cells and has shown significant efficacy in multiple sclerosis (MS) patients in Phase 2 studies. The efficacy of anti-CD20 therapy, including the reduction of lesion formation, is hypothesized to be directly related to the extent of peripheral B cell depletion. However, ofatumumab is the first anti-CD20 antibody where this hypothesis has been tested in a full-scale dose finding study (MIRROR). 
Design/Methods: In the Phase 2 MIRROR study, a total of 231 relapsing-remitting MS (RRMS) patients were randomized (2:1:1:1:2) to placebo or ofatumumab 3, 30, 60 mg for every 12 weeks, or 60 mg every 4 weeks. Patients received treatment for 24 weeks and were followed up for an additional 24 weeks. B cell counts and Gd+ lesion counts were assessed at screening and every 4 weeks until the end of the study. A quasi-Poisson regression model was developed relating new Gd+ lesion counts to the average B cell levels at weeks 4 to 20, the number of lesions at baseline, and the treatment group. 
Results: The model showed that depletion of B cell counts is significantly associated with superior control of Gd+ lesions. Efficacy of any ofatumumab treatment regimen in controlling Gd+ lesions was explained solely by the extent of B cell depletion caused by the different dosing regimen. 
Conclusions: The model indicated that low B cell counts over time, achieved and consistently maintained under ofatumumab treatment, are essential for efficacious control of lesion counts.
Recently we proposed that memory B cell numbers are important indicators of whether treatments work. If this is the case on may hope that their numbers correlate with disease activity. In this study they look at efficacy and B cell numbers and conclude that there is a link between efficacy and CD19 B cell depletion. People with lower B cell levels had less accumulation of  MRI lesions. Those below 8 CD19 B cells per microlitre of blood did the best. This would equate to about 2-4 memory B cells. It would have been nice to see that memory T cell levels didn't have any influence However this suggests that we may be on the right track 

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