Monoclonal Antibody Therapy

Monoclonal antibodies are engineered immunoglobulins that bind one target with high specificity. They treat cancer, autoimmune and inflammatory disease, infection, asthma, migraine, osteoporosis, hyperlipidaemia and transplant rejection. They are given by injection or infusion, have long half-lives and cause class-specific problems: infusion reactions, immunogenicity, infection and cytokine release.

Naming. The suffix shows the source: -omab (murine), -ximab (chimeric, mouse variable region), -zumab (humanised) and -umab (fully human). Murine and chimeric antibodies carry more hypersensitivity and antidrug antibody risk.

Mechanisms. Antibodies neutralise a soluble ligand (adalimumab, bevacizumab), block a receptor (trastuzumab, cetuximab), deplete cells through complement or cell killing (rituximab), carry a toxin or drug (antibody-drug conjugates), engage T cells (bispecific antibodies), or release immune checkpoints (pembrolizumab, nivolumab).

Pharmacokinetics. Not absorbed orally and not metabolised by the liver. Clearance is by protein breakdown and, for many, receptor-mediated uptake. Half-life is usually 2 to 4 weeks. Subcutaneous bioavailability is 50 to 80%. High tumour burden, inflammation, low albumin and antidrug antibodies speed clearance.

Biosimilars. Highly similar copies with equivalent efficacy and safety, approved after comparison with the reference product. Switching between biosimilars is generally safe with a plan for monitoring.

Preparation. Store at 2 to 8 degrees Celsius; do not freeze or shake; dilute in sodium chloride 0.9% unless the label states glucose; use an in-line 0.2 micron filter when specified.

• First-line. Chosen when the target is validated for the disease: HER2-positive breast cancer (trastuzumab), CD20 lymphoma (rituximab), PD-1 expressing tumours (checkpoint inhibitors), TNF-driven disease after csDMARD failure.
• Alternative. Another antibody to a different target when response is inadequate or antidrug antibodies develop.
• Specialist. Rare disease antibodies, bispecific antibodies, antibody-drug conjugates and CAR-T supportive therapy such as tocilizumab for cytokine release.
• Emergency. Cytokine release syndrome, anaphylaxis to infusion and immune-related toxicity of checkpoint inhibitors.

Selection. Confirm the biomarker or target first, screen for tuberculosis and hepatitis B where immunosuppression is expected, and choose route and interval that the patient can sustain.

Infusion reactions. Give premedication (paracetamol 1 g, an antihistamine, and a glucocorticoid for first rituximab or cetuximab doses). Start at a slow rate and increase in steps. For a reaction, stop the infusion, treat symptoms, and restart at half the rate once settled. For anaphylaxis give adrenaline 0.5 mg intramuscularly and stop the drug.

Contraindications. Prior anaphylaxis to the same antibody or excipient; active serious infection for immunosuppressive antibodies; live vaccines during treatment; pregnancy for several agents.

Serious adverse effects.

• Infusion reactions and anaphylaxis, mostly with the first infusion.
• Serious infection and reactivation of tuberculosis and hepatitis B.
• Cytokine release syndrome with T cell engaging and CD20 antibodies.
• Immune-related toxicity with checkpoint inhibitors (colitis, hepatitis, pneumonitis, endocrine failure).
• Target-specific toxicity: cardiomyopathy (trastuzumab), skin rash (cetuximab), hypertension and bleeding (bevacizumab), osteonecrosis of the jaw (denosumab).

Major interactions. Few pharmacokinetic interactions. Pharmacodynamic risks arise from combining immunosuppressants, live vaccines, anthracyclines with trastuzumab and anticoagulants with bevacizumab. Inflammation can alter drug clearance.

Common prescribing errors.

• Giving without premedication or at too fast a rate.
• Missing hepatitis B and tuberculosis screening.
• Dosing by the wrong weight or confusing weight-based with fixed dosing.
• Substituting biosimilars without a plan to monitor.
• Delaying treatment of immune-related toxicity.

Special groups.

• Pregnancy: IgG crosses the placenta mainly after 16 weeks; avoid unless benefit is clear; delay live vaccines in the infant.
• Breastfeeding: little oral absorption; usually acceptable.
• Children: weight or surface area dosing for many; specialist care.
• Older adults: higher infection risk; check cardiac function before trastuzumab.
• Kidney and liver: little adjustment, since clearance is not renal or hepatic.
• East Africa: tuberculosis, hepatitis B and HIV are common, so screen before immunosuppressive antibodies; cost and cold chain are the main limits; biosimilars and access programmes can widen supply.

Monitoring. Vital signs during and after infusion; full blood count, liver tests and infection review at set intervals; drug-specific tests (echocardiogram, thyroid function, glucose); antidrug antibodies and trough levels where available.

Referral and escalation. Anaphylaxis; severe or opportunistic infection; cytokine release syndrome; severe immune-related toxicity; loss of response.

Comparison with alternative classes. Monoclonal antibodies are highly specific and long acting, but costly, injected and immunogenic. Small molecule drugs are oral and cheaper but less selective, with more drug interactions.