Rituximab: Anti-CD20 Antibody for Lymphoma, RA and Neurology
Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen expressed on the surface of B-lymphocytes. First approved in 1997 for the treatment of non-Hodgkin lymphoma, rituximab revolutionized the management of B-cell malignancies and later became a cornerstone therapy in autoimmune diseases including rheumatoid arthritis and multiple sclerosis variants.
By selectively depleting CD20-positive B cells while sparing plasma cells and haematopoietic stem cells, rituximab offers a targeted approach that preserves some immune function. Biosimilar versions have significantly expanded access since the originator patent expired, and rituximab is now on the WHO Model List of Essential Medicines.
Mechanism of Action
Rituximab binds with high affinity to CD20, a transmembrane protein expressed on pre-B cells through mature B lymphocytes but absent on stem cells and plasma cells. Binding initiates B-cell depletion through three complementary mechanisms: complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and direct induction of apoptosis. CD20 does not shed from the cell surface and does not internalize upon antibody binding, making it an ideal target for sustained receptor engagement. B-cell depletion in peripheral blood is typically complete within two to four weeks of the first infusion, with recovery starting six to twelve months later depending on dose and indication.
Indications
Approved oncological indications include follicular lymphoma, diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukaemia (in combination with chemotherapy), and mantle cell lymphoma. In rheumatology, rituximab is approved for rheumatoid arthritis refractory to anti-TNF therapy, in combination with methotrexate. Neurological approvals include neuromyelitis optica spectrum disorder (NMOSD) and pemphigus vulgaris. Off-label use is widespread in conditions such as granulomatosis with polyangiitis, systemic lupus erythematosus, immune thrombocytopenia, and membranous nephropathy.
Dosage and Administration
Rituximab is administered exclusively as an intravenous infusion. In lymphoma, standard dosing is 375 mg/m² body surface area per infusion cycle. In rheumatoid arthritis, two infusions of 1000 mg each are given two weeks apart, repeated every six months based on disease activity. Subcutaneous formulations of rituximab are approved in some indications and allow faster administration after the first IV cycle is completed without infusion reactions. Pre-medication with antihistamines, paracetamol, and corticosteroids is mandatory to reduce infusion reactions.
Side Effects
Infusion-related reactions occurring during the first infusion affect up to 77 percent of patients and include fever, chills, rigors, hypotension, and bronchospasm; the incidence and severity decrease substantially with subsequent infusions. Serious infections are a major safety concern given profound B-cell depletion; pneumonia, sepsis, and reactivation of latent infections including hepatitis B virus (HBV) can be life-threatening. All patients must be screened for HBV before starting rituximab, and antiviral prophylaxis is required in carriers and resolved infection. Progressive multifocal leukoencephalopathy (PML) caused by JC virus reactivation has been reported, particularly in heavily immunosuppressed patients. Hypogammaglobulinaemia develops with repeated cycles and may necessitate immunoglobulin replacement.
Interactions
Concomitant use with other immunosuppressants including methotrexate, azathioprine, and corticosteroids increases the risk of severe infections. Live vaccines are absolutely contraindicated during and for at least twelve months after rituximab therapy; vaccine responses may be blunted for up to two years. Cisplatin combination with rituximab in renal toxicity studies showed additive nephrotoxicity. Antihypertensive medications may need dose adjustment as hypotension during infusion is common.
Special Notes
Rituximab is a prescription-only medicine administered in specialised centres. Hepatitis B screening (HBsAg, anti-HBc) is mandatory before each treatment course. Patients with active severe infections should not receive rituximab until infections are controlled. Fertility effects are not well characterised; use during pregnancy is contraindicated due to potential foetal B-cell depletion. Effective contraception is required during and for twelve months after treatment. Biosimilar substitution should follow national pharmacy regulations and be confirmed with the prescribing physician.
Related Topics
Frequently Asked Questions
Why is hepatitis B screening mandatory before rituximab?
Rituximab causes deep B-cell depletion, which can allow hepatitis B virus that is latent in liver cells to reactivate without immune control. Reactivation can cause fulminant hepatitis and liver failure. Screening identifies carriers who require antiviral prophylaxis before and during therapy.
How long does B-cell depletion last after rituximab?
After a standard course, peripheral B cells typically begin recovering at six to nine months and reach normal levels at twelve to eighteen months. Deeper or more prolonged depletion occurs with repeated cycles. During this window, infection risk remains elevated and live vaccines should not be given.
Can rituximab be given to patients with rheumatoid arthritis who failed anti-TNF therapy?
Yes, rituximab combined with methotrexate is specifically approved for moderate to severe RA in patients who have had an inadequate response to or are intolerant of anti-TNF agents. It represents a mechanistically distinct option that targets B cells rather than TNF-mediated inflammation.
Sources
- EMA: Rituximab (MabThera) Summary of Product Characteristics 2023
- EULAR RA Management Guidelines 2022
- Flowers CR et al: Rituximab in Lymphoma. J Clin Oncol 2022