Abstract Details

Title The Relationship Between Peripheral B-Cell Levels and MRI Disease Activity in Relapsing Remitting Multiple Sclerosis (RRMS)

Topic Multiple Sclerosis

Presentation(s) (-)

Poster/Presentation
Number 009

Objective

Background B-cells have been implicated in the pathogenesis of disease in RRMS. Studies of supra-pharmacological anti-CD20 B-cell depletion have shown reduced disease activity but no relationship between B-cells and efficacy. OMS112831 is an ongoing Phase 2B placebo-controlled dose-ranging study of subcutaneous (SC) ofatumumab in RRMS. Headline safety and efficacy data are presented elsewhere (Presentations: S23.006, I7.1.007). The wide range of studied doses (3-180 mg) modulates B-cell depletion providing additional opportunities to explore relationships between B-cells and disease activity.

Design/Methods Study OMS112831 is evaluating the inhibition of new GdE lesions during a 12-week placebo controlled period. Weighted mean CD19 B-cell count for the period 4-12 weeks were correlated to the number of new GdE lesions on an individual patient basis (n=231). A non-parametric analysis was used to identify threshold effects and generalized linear models used to identify relationships between peripheral B-cell levels and MRI disease activity.

Results Analysis of cumulative new GdE lesions showed disease activity was significantly reduced below a threshold CD19 count of 64 cells/uL for the period 4-12 weeks. A generalized linear model with underlying negative-binomial distribution accounting for over-dispersion of lesions across patients showed a highly significant linear relationship (P<0.001) with residual annualized disease activity of one new lesion per year and a threshold of approximately 32-64 cells/uL.

Conclusions This dose-response study of anti-CD20 therapy in RRMS demonstrates modulation of pharmacological and clinical effects. Relating peripheral B-cell pharmacology to appearance of new GdE lesions reveals a potential threshold of 32-64 cells/uL for significantly reducing MRI lesion activity. These results present a possible new target threshold for exploration of therapeutic benefit in RRMS patients undergoing anti-CD20 therapy.

Authors/Disclosures
Daren J. Austin, PhD	No disclosure on file
Sudarshini Ramanathan, MBBS, PhD, FRACP (University of Sydney)	Dr. Ramanathan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Ramanathan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen, Alexion, Novartis. Dr. Ramanathan has received research support from NHMRC, RACP, University of Sydney.
Immanuel Freedman, PhD	No disclosure on file
	No disclosure on file
Jerry M. Tolson, PhD (Glaxco Smith Kline)	No disclosure on file
Susan Vanmeter, MD	Dr. Vanmeter has received personal compensation for serving as an employee of UCB. Dr. Vanmeter has stock in UCB.

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