B Cell Targeted Therapy

B cell targeted therapy removes or inhibits B lymphocytes. Rituximab depletes CD20-positive B cells and treats rheumatoid arthritis, ANCA-associated vasculitis, pemphigus, immune thrombocytopenia, lymphoma and chronic lymphocytic leukaemia. Belimumab inhibits B cell survival factor (BAFF) in lupus; ocrelizumab, ofatumumab and obinutuzumab are other anti-CD20 antibodies.

Mechanism. Anti-CD20 antibodies cause B cell lysis through complement, antibody-dependent cytotoxicity and apoptosis. Plasma cells lack CD20, so existing antibody titres fall slowly. B cells recover 6 to 12 months after a course.

Pharmacokinetics. Rituximab half-life 20 days after first dose, longer with repeats; clearance rises with high tumour burden or proteinuria.

Rituximab dosing.

• Rheumatoid arthritis: 1000 mg intravenously on days 1 and 15, repeated every 6 to 12 months based on disease activity (with methotrexate).
• ANCA vasculitis: 375 mg/m2 weekly for 4 weeks, or 1000 mg twice 2 weeks apart; maintenance 500 mg every 6 months.
• Pemphigus: 1000 mg on days 1 and 15, then 500 mg at months 12 and 18.
• Lymphoma: 375 mg/m2 with chemotherapy each cycle.
• Premedication with paracetamol, chlorphenamine and methylprednisolone 100 mg intravenously before each infusion.

Biosimilars. Rituximab biosimilars are available and equal in effect.

Belimumab. 10 mg/kg intravenously every 2 weeks for 3 doses, then every 4 weeks; or 200 mg subcutaneously weekly. For active lupus with high disease activity or nephritis.

• First-line. CD20 lymphomas with chemotherapy; ANCA-associated vasculitis (remission induction and maintenance); pemphigus vulgaris.
• Alternative. Rheumatoid arthritis after TNF inhibitor failure, or in patients with lymphoma history, latent tuberculosis or demyelination.
• Specialist. Refractory lupus and lupus nephritis, immune thrombocytopenia, membranous nephropathy, autoimmune haemolytic anaemia, myasthenia gravis, multiple sclerosis (ocrelizumab).
• Emergency. Life-threatening vasculitis or thrombotic thrombocytopenic purpura with plasma exchange and glucocorticoid.

Selection. Use when T cell and cytokine targeted drugs have failed, or when the disease is antibody mediated. Check hepatitis B first, because reactivation can be fatal.

Contraindications. Active severe infection; hepatitis B surface antigen positivity without antiviral cover; severe heart failure; hypersensitivity to murine protein; live vaccines.

Serious adverse effects.

• Infusion reactions (fever, chills, rash, hypotension, bronchospasm), mainly with the first dose.
• Hepatitis B reactivation; progressive multifocal leukoencephalopathy (rare).
• Hypogammaglobulinaemia and recurrent infection; late-onset neutropenia.
• Pneumocystis pneumonia with concurrent steroids and cyclophosphamide.
• Impaired vaccine response.

Major interactions. Antihypertensives (hold 12 hours before infusion because of hypotension); live vaccines; other immunosuppressants add infection risk.

Common prescribing errors.

• Not screening hepatitis B surface antigen and core antibody.
• Not giving premedication.
• Vaccinating during B cell depletion.
• Missing immunoglobulin level monitoring.
• No pneumocystis prophylaxis when combined with high-dose steroids.

Special groups.

• Pregnancy: avoid; effective contraception for 12 months after the last dose; neonatal B cell depletion possible.
• Breastfeeding: low milk transfer; specialist advice.
• Children: weight or surface area dosing; specialist.
• Older adults: cardiac and infection risk.
• Kidney: no adjustment.
• Liver: hepatitis B prophylaxis (entecavir or tenofovir) throughout and for 12 months after.
• East Africa: hepatitis B is common and HIV, tuberculosis and Pneumocystis risk is high, so screen all patients and give prophylaxis; rituximab is costly, though a biosimilar and use in lymphoma are established.

Monitoring. Hepatitis B serology; CD19 or CD20 counts; immunoglobulins before each course; blood count; infusion observation for 1 to 2 hours; infection symptoms.

Referral and escalation. Infusion anaphylaxis; hepatitis flare; new neurological symptoms; severe or recurrent infection; low immunoglobulin with infections.

Comparison with alternative classes. Anti-B cell therapy suits antibody-mediated disease and has long dosing intervals, but suppresses vaccine response and needs hepatitis B vigilance. TNF inhibitors act faster in arthritis.