Association of B cell Subsets and Aquaporin-4 antibody titers with Disease Activity in Participants in the N-MOmentum trial Receiving Inebilizumab Treatment (S5.005)

Objective:

To evaluate the relationship between peripheral blood B-cell subsets and aquaporin-4 (AQP4) immunoglobulin G (IgG) titers and NMOSD attacks in participants of N-MOmentum (NCT02200770).

Background:

Inebilizumab (INEB), an anti-CD19 B-cell depleting antibody, is approved to treat neuromyelitis optica spectrum disorder (NMOSD).

Design/Methods:

Participants received INEB 300 mg or placebo (PBO), on days 1 and 15 during the randomized controlled period (RCP) and every 6 months in the optional open-label period (OLP). Absolute counts of CD20⁺ B cells and CD27⁺ memory B cells were assessed by flow cytometry (RCP + OLP). Plasma cell (PC) gene expression was assessed by quantitative reverse transcription PCR (RT-qPCR) in the RCP. AQP4-IgG titers were determined by cell-based assay (RCP only). All measurements were done in peripheral blood.

Results:

In PBO-treated participants, the observed levels of CD20⁺ B Cells (p<0.01), and CD27⁺ Memory B Cells were increased at the time of NMOSD attack relative to the preceding study visit. Increases in PC subset were already observed at the preceding visit relative to baseline (p<0.01). During attack, a >2-fold increase from baseline was seen in 4/20 (20%) for CD20⁺ B cells, 3/19 (16%) for memory B cells, and 11/20 (55%) for PC. INEB significantly decreased all B cell subsets. No significant increases in B cell subsets at time of attack were observed in the INEB group relative to the preceding visit. Changes in AQP4-IgG titer from baseline to attack were not significantly different between treatment groups (p=0.15). At RCP end, 9/50 (18%) of PBO participants vs 59/159 (37%) of INEB participants (p=0.014) had ≥ 2-fold decrease in AQP4-IgG (0% vs 11% ≥8-fold decrease, p=0.008).

Conclusions:

Increased levels of B-cell subsets at time of attack were observed in the PBO but not INEB group, particularly in the PC subset. Inebilizumab treatment was associated with reduction in AQP4-IgG in a subset of participants. Disclosure: Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe PC (MTPC). The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aarhus University. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CELGENE. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACRELION. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizter. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck Serono. The institution of Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aprilbio, HanAll BioPharma, Viela Bio. Dr. Kim has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion, Biogen, Celltrion, Eisai, Merck Serono, Novartis, Sanofi Genzyme, Teva-Handok. Dr. Kim has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Multiple Sclerosis Journal, Journal of Clinical Neurology. Michael Smith has nothing to disclose. William Rees has received personal compensation for serving as an employee of Horizon Therapeutics. William Rees has received personal compensation for serving as an employee of Viela Bio. William Rees has received stock or an ownership interest from Horizon Therapeutics. William Rees has received stock or an ownership interest from Viela Bio. William Rees has received intellectual property interests from a discovery or technology relating to health care. William Rees has received intellectual property interests from a discovery or technology relating to health care. Dr. Patterson has received personal compensation for serving as an employee of Hospital of the University of Pennsylvania. Dr. Patterson has stock in Horizon Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atara. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gossamer Bio. Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Therini. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. Dr. Cree has received publishing royalties from a publication relating to health care. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon Therapeutics. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reistone Bio. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Antigenomycs. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MedEdicus. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ImCyse. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Podoll. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Patterson. The institution of Dr. Bennett has received research support from Novartis. The institution of Dr. Bennett has received research support from Alexion. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.