Rituximab wipes out the body's B cells so healthy ones can regrow
Rituximab is a lab-made antibody that latches onto CD20, a protein carried by the immune system's B cells, and marks them for destruction. Approved in 1997 for stubborn lymphomas, it now treats leukaemia, rheumatoid arthritis and rare forms of vasculitis, and it sits on the World Health Organization's list of essential medicines.
The drug is a chimeric monoclonal antibody, sold as Rituxan among other names and given by slow intravenous drip. CD20 appears on B cells from the early pre-B stage onwards but is missing from plasma cells and blood-forming stem cells, so those survive while normal and diseased B cells alike are cleared. Once the old population is gone, fresh healthy B cells can develop from lymphoid stem cells. The antibody's tail recruits the body's own killing machinery, known as antibody-dependent and complement-dependent cytotoxicity. Cells carrying little CD20 tend to escape.
One curious detail: rituximab gathers on one side of a B cell, dragging proteins into a cap. When a natural killer cell grabbed that cap, it destroyed the target 80% of the time, against 40% for B cells lacking the lopsided cluster.
IDEC Pharmaceuticals developed it as IDEC-C2B8, and the US patent ran from 1998 until 2015. The FDA first cleared it in 1997 for B-cell non-Hodgkin lymphomas that resisted other chemotherapy, and paired with CHOP chemotherapy it beats CHOP alone in diffuse large B-cell lymphoma. Later approvals covered rheumatoid arthritis after TNF blockers fail, adults with granulomatosis with polyangiitis in 2011, children two and older with that disease in 2019, and an under-the-skin version in the EU in 2016. Doctors also use it off-label for hard cases of multiple sclerosis and lupus, with some evidence it works but less certainty about safety.
Infusion reactions such as fever and chills are the commonest side effects. Rarer dangers include reactivation of hepatitis B and progressive multifocal leukoencephalopathy, a usually fatal brain infection caused by JC virus reawakening, though very few cases have been recorded in autoimmune patients. Because it strips out antibody-making cells, vaccines can struggle: people with multiple sclerosis on the drug faced higher risk of severe COVID-19, yet nine of ten who waited for B cell counts to recover before re-dosing made protective antibodies after the Pfizer–BioNTech shot. Whether it is safe in pregnancy is unclear.
Source: Rituximab
