Rituximab is able to inhibit the B-cells in the pathogenesis of RA. The drug is a chimeric monoclonal antibody against the protein CD20 present on the B-cell surface. Rituximab destroys B-cells in the joints via different mechanisms, helping to reduce inflammation.
The exact function of CD20 is unknown, but it may play a role in Ca2+ influx across plasma membranes, maintaining intracellular Ca2+ concentration and allowing activation of B cells. The following effects of rituximab have been found:
- the Fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (ADCC), which leads to phagocytosis by macrophages. (1)
- activation of the complement cascade, which generates the membrane attack complex (MAC) that can directly lyse B cells by complement-mediated cytotoxicity (CDC). (2)
- interaction with natural killer cells resulting in direct lysis. (3)
- a general regulatory effect on the cell cycle.
- increase in MHC II and adhesion molecules.
- downregulation of the B-cell receptor.
- apoptosis of CD20+ cells.
Rituximab is used in the treatment of RA as well as in B cell non-Hodgkin's lymphoma and B-cell leukemias.
Serious adverse events, which can cause death and disability, include: severe infusion reactions, cardiac arrest, acute renal failure, infections, immune toxicity, and pulmonary toxicity.
EPAR of rituximab.