Rituximab is used to treat CD20-positive cancers like NHL and CLL, and autoimmune diseases such as rheumatoid arthritis, pemphigus vulgaris, and certain vasculitis disorders. It is also approved for use in children with B-cell cancers, can be combined with chemotherapy, and is available in IV and subcutaneous forms. A rare serious risk is PML.

Rituximab works by binding to the CD20 protein on B cells, helping the immune system target and destroy them. It triggers immune responses like ADCC, CDC, and apoptosis, and also increases the sensitivity of cancer cells to chemotherapy. It is less effective when CD20 expression is low. By clearing abnormal B cells while sparing stem cells and plasma cells, healthy B cells can later regenerate.

Rituximab is given as either an IV infusion or a subcutaneous injection. IV doses start slowly with monitoring and premedication, with faster infusions possible later if tolerated. The subcutaneous form (with hyaluronidase) is usually given after at least one IV dose. Dosing schedules vary by condition and may be used alone or with chemotherapy.

Rituximab can cause infusion reactions such as fever, chills, nausea, rash, and low blood pressure, especially during the first dose. Other effects may include fatigue, infections, and low blood cell counts. Less common but serious risks include severe infections, heart or kidney problems, and bowel issues. A rare but potentially fatal side effect is PML, so careful monitoring is essential.

Rituximab should not be used in patients with known allergies to the drug or those with severe reactions to monoclonal antibodies. Caution is required in patients with active infections, especially hepatitis B, and screening is recommended before treatment. Care is also needed in those with heart or lung disease due to possible infusion reactions. Live vaccines should be avoided, and close monitoring is important during and after treatment.

Rituximab is an important treatment for cancers and autoimmune diseases involving CD20-positive B cells. It is effective alone or with other therapies, but requires monitoring due to risks like infections and infusion reactions. With proper precautions, it remains a key therapy for B-cell disorders.

Response to rituximab can be influenced by CD20 expression levels, tumor burden, Fc gamma receptor (Fc?R) polymorphisms, and the presence of complement inhibitors. Patients with higher CD20 density and certain Fc?R genotypes tend to respond better.

Resistance can occur due to CD20 downregulation, mutations in CD20, overexpression of complement regulatory proteins (e.g., CD55, CD59), or changes in apoptotic signaling pathways. Repeated exposure may also lead to selection of CD20-negative clones.

Rituximab is frequently combined with chemotherapy (e.g., CHOP, FCR) to enhance efficacy through synergistic effects. In autoimmune diseases, it may be used with immunosuppressants like methotrexate or corticosteroids to improve disease control.

Clinical trials (e.g., SABRINA and MabEase) have shown that subcutaneous rituximab, combined with hyaluronidase, provides similar efficacy, pharmacokinetics, and safety profiles to IV infusion, with the benefit of reduced administration time.

Rituximab depletes circulating B cells, potentially impairing humoral immunity for months. This can reduce vaccine efficacy and increase the risk of infections, particularly in patients on long-term or repeated therapy. Immunoglobulin levels, especially IgG, may need monitoring.

Rituximab carries a high risk of hepatitis B reactivation. All patients should be screened before treatment. Those with a history of HBV should receive prophylactic antiviral therapy and close monitoring during and after treatment.

These reactions are primarily cytokine-mediated and occur due to rapid lysis of B cells, leading to the release of inflammatory cytokines. They are more common during the first infusion and in patients with high tumor burden.