Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses
Status:
Completed
Trial end date:
2019-02-15
Target enrollment:
Participant gender:
Summary
Ublituximab (also known as LFB-R603) is a monoclonal antibody that specifically binds to the
trans-membrane antigen CD20. The binding induces immune response that causes lysis of B
cells.
The rationale for using ublituximab in neuromyelitis optica (NMO) and neuromyelitis optica
spectrum disorder (NMOSD) is based on the known roles of B cells, antibody production and
plasma cells in the pathophysiology of NMO. NMO is characterized by the presence of an
anti-Aquaporin-4 (AQP4) antibody, which can only be produced by differentiation of B cells to
plasma cells. Because these anti-AQP4 antibodies may be pathogenic, B cells recognizing AQP4
may be directly involved in the disease process as well. B cells also play a role as potent
antigen presenting cells in NMO. The strongest evidence of the importance of B cells in NMO
comes from studies of B cell depletion, most commonly with anti-CD20 monoclonal antibody,
rituximab (Rituxan®).
Rituximab has been shown in five retrospective and two prospective studies to be effective in
reducing NMO relapses up to 90% and achieving remission in up to 80% of patients solely by
its action on CD20+ B cells, despite no change in plasma cell population and anti-AQP4
antibody titers. These human trials strongly suggest a critical role for B cells in the
pathophysiology of human disease. While typically used in the prevention of disease, B-cell
depletion may be beneficial in the treatment of an acute relapse as well. Emerging evidence
indicates that peripheral B cells are activated during a relapse and plasmablast production
of anti-AQP4 antibodies spikes. B cells are also found within acute lesions of the spinal
cord and optic nerve suggesting roles both in the blood and in the central nervous system
during a relapse.