Inebilizumab reduces B-cell subsets in neuromyelitis optica spectrum disorder attacks

Treatment with inebilizumab was associated with reduction in aquaporin-4 antibody titers and B cells for those with neuromyelitis optica spectrum disorder, according to an expert at ECTRIMS 2022.

“The prominent role B cells play in [neuromyelitis optica spectrum disorder] disease activity is well-documented at this point, but the relationship between attacks and peripheral B-cell subsets, particularly plasma cells and plasma blasts, has not been as clear,” Bruce A. Cree, MD, PhD, professor of clinical neurology at the Weill Institute for Neurosciences at the University of California, San Francisco, told Healio.

Cree and fellow researchers sought to evaluate the relationship between peripheral blood B-cell subsets and aquaporin-4 (AQP4) IgG titers and neuromyelitis optica spectrum disorder (NMOSD) attacks in patients in the N-MOmentum trial.

Participants in the phase 3 trial received 300 mg of Uplizna (inebilizumab, Horizon Therapeutics) or placebo on days 1 and 15 during the randomized controlled period, followed by 6-month dosing intervals in the optional open-label period. Researchers evaluated absolute counts of CD20+ B cells and CD27+ memory B cells via flow cytometry and plasma cell gene expression via quantitative reverse transcription polymerase chain reaction. AQP4-IgG titers were assessed using cell-based assay in the randomized controlled period.

According to results, participants in the placebo group had significant increases in CD20+ B cells and CD27+ memory B cells at time of attack in relation to the previous visit, as well as increases in plasma cell gene expression subset. During attack, researchers reported a greater than twofold increase from baseline in 20% for CD20+ B cells, 16% for memory B cells and 55% for plasma cell gene expression.

Conversely, inebilizumab significantly decreased all B-cell subsets, with no significant increases in any B-cell subset observed at the time of attack in relation to the previous visit.

In addition, researchers reported no significant changes in AQP4-IgG titer from baseline to attack between treatment groups. At the end of the randomized controlled period, 18% of those given placebo had at least a twofold decrease in AQP4-IgG compared with 37% of the inebilizumab cohort, with 0% and 11%, respectively, experiencing at least an eightfold decrease.

“These findings showed that plasma cell gene signature expression was higher before and during NMOSD attacks among those given the placebo, but in the Uplizna-treated group, the level of expression remained at similar levels throughout the study,” Cree told Healio. “This analysis has offered important insight into potential biomarkers for disease activity in NMOSD that should be studied further.”