Precision therapy for neuromyelitis optica spectrum disorder: A retrospective analysis of the use of class-switched memory B-cells for individualised rituximab dosing schedules

Abstract

Background: B-cell depleting treatments are widely used to modify the course of neuromyelitis optica spectrum disorder (NMOSD). Despite recent successful Phase 3 trials of several novel NMOSD therapies, limited availability and high cost constrains their clinical use, and rituximab (RTX) remains a core treatment in many centres. Since 2013, the Royal Prince Alfred Hospital Neuroimmunology Clinic (NIC) has regularly measured class-switched memory B-cells (SMB-cells) in the peripheral blood of patients with NMOSD, who have been treated with RTX, in order to guide retreatment intervals.

Objective: To assess the management and outcomes of the treated patients, and to determine the effect of SMB-cell monitoring in guiding retreatment intervals.

Methods: A retrospective analysis of hospital records, clinic letters and laboratory data was performed.

Results: Sixteen patients with NMOSD received individualised rituximab dosing at NIC between 2013 and 2018. Fourteen (87.5%) were aquaporin-4 antibody (AQP4-Ab) positive; 1 (6.25%) was myelin oligodendrocyte glycoprotein antibody (MOG-Ab) positive and 1 (6.25%) was seronegative. After commencement of RTX, individually dosed according to regular measurements of serum SMB-cells, there was a 77.5% reduction in annualised relapse rate over a mean follow-up time of 46.1 months in our recently active NMOSD patients. Their mean retreatment interval was 50.9 weeks.

Conclusions: This study provides real-world evidence supporting individualised rituximab dosing in the treatment of NMOSD.

Keywords: Biomarkers; Disease modifying therapies; Memory B-cells; Neuromyelitis optica (NMO); Rituximab.