Individualized B cell-targeting therapy for neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system characterized by severe attacks of optic neuritis (ON), longitudinally extensive transverse myelitis (LETM), and area postrema syndrome. The majority of patients with NMOSD are seropositive for autoantibodies against the astrocyte water channel aquaporin-4 (AQP4). As convergent clinical and laboratory-based investigations have indicated that B cells play a fundamental role in NMO immunopathology, B cells have become an attractive therapeutic target. Rituximab is a therapeutic monoclonal antibody against CD20 expressed on B cells and increasingly used for the treatment of NMOSD. Although there is robust evidence for the efficacy and safety of rituximab in NMOSD, considerable variability has been noted in biological and clinical responses in patients. Therefore, the focus now is on understanding the mechanisms underlying the variability in response to rituximab and optimizing the use of rituximab for NMOSD. Identification of biomarkers for prediction of clinical response, and effective dosing and timing of treatment may provide useful tools for patient-tailored treatment in NMOSD. Herein, we review current evidence on factors that affect biological and clinical responses to rituximab and highlight the importance of individualized therapies for NMOSD.