Abstract Details

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

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).

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.

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).

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.