Abstract Details

Title Efficacy of Ofatumumab on Microglial Activity in Patients with Relapsing forms of Multiple Sclerosis: Interim Analysis

Topic Multiple Sclerosis

Presentation(s) S14 - MS Therapeutics (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

Background The potential impact of ofatumumab on microglial activation in MS is unknown.

Objective Determine the effect of ofatumumab on microglial activation using [F-18]PBR06 PET targeting 18kilodalton-translocator protein (TSPO) in RMS patients.

Design/Methods 20 [F-18]PBR06 PET scans in 5 RMS patients (mean age 40.2±12 years, 4 females, median EDSS 3.0, mean T25FW 4.25±0.54 seconds) were performed prior to, and at days 5, 28 and 90 after initiating ofatumumab. Peripheral CD19 counts and clinical evaluations were also performed. Individualized z-score maps of brain parenchymal microglial activation were generated by voxel-by-voxel comparison between each subject's PET SUVR images and a control dataset of 9 healthy individuals. Glial activity load on PET (‘GALP’) was calculated as the sum of voxel-by-voxel z-scores ≥4 in the lesional and perilesional normal-appearing white matter (LWM and P-NAWM), cortical grey matter (CoGM) and thalamic (Th) regions of interest (ROI) in standard atlas space. Mean ROI GALP scores, peripheral CD19 counts, and clinical measurements over 90 days were compared with baseline values. p<0.05 was considered statistically significant.

Results Mean CoGM-GALP was significantly decreased at 90 days but not at days 5 or 28, post-ofatumumab initiation, as compared to BL (0.75±0.09 vs. 0.93±0.06, -19.4%, p<0.05). Absolute and %CD19 counts were significantly decreased at day 5 vs BL (11.5±9.1 vs. 256.6±117.4 cells/µL, -96%, p=0.01 and 0.98±0.98% vs. 14.7±8.7%, -93%, p=0.02), which persisted at day 90. There was no statistically significant difference in mean GALP scores in Th, LWM, and P-NAWM, or in clinical measurements over 90 days (all p>0.05).

Conclusions Ofatumumab treatment was associated with decreased CoGM microglial activation at 3 months and was preceded by peripheral CD19+ cell depletion at day 5, which may suggest an indirect, downstream effect of B-cell depletion on microglial activity in RMS patients. Further studies on effects of ofatumumab on microglial activation are warranted.

Authors/Disclosures
Tarun Singhal, MD (Brigham And Women's Hospital) PRESENTER	Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Singhal has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana LifeSciences. The institution of Dr. Singhal has received research support from Novartis. The institution of Dr. Singhal has received research support from Department of Defense. The institution of Dr. Singhal has received research support from Foundation for Neurologic Diseases.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Gauruv Bose, MD (The University of Ottawa and Ottawa Hospital Research Institute)	Dr. Bose has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bose has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Bose has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva Pharmaceuticals. The institution of Dr. Bose has received research support from Multiple Sclerosis Society of Canada.
Bonnie Glanz (Brigham and Women'S Hospital)	The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH.
Jonathan D. Zurawski, MD (Brigham & Women's Hospital)	The institution of Dr. Zurawski has received research support from The Race to Erase MS Foundation. The institution of Dr. Zurawski has received research support from Novartis Pharmaceuticals. The institution of Dr. Zurawski has received research support from I-Mab Biopharma . The institution of Dr. Zurawski has received research support from Elizabeth A. Kremer MS Research Foundation. The institution of Dr. Zurawski has received research support from Novartis.
Steven Cicero	No disclosure on file
Maria K. Houtchens, MD	Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche . Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Serono. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cravath. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Beasley . Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen. The institution of Dr. Houtchens has received research support from Genzyme. The institution of Dr. Houtchens has received research support from Biogen. The institution of Dr. Houtchens has received research support from Genentech.
Christopher Severson, MD	Dr. Severson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Severson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech.
Shipra Dubey	No disclosure on file
	No disclosure on file
Brandon Brown, PharmD	Dr. Brown has received personal compensation for serving as an employee of Novartis. Dr. Brown has stock in Novartis.
Rohit Bakshi, MD, FAAN	Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. An immediate family member of Dr. Bakshi has received stock or an ownership interest from Biogen. The institution of Dr. Bakshi has received research support from BMS/Celgene. The institution of Dr. Bakshi has received research support from EMD Serono.
Harald Kropshofer	Harald Kropshofer has nothing to disclose.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Siemens. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..
	No disclosure on file