Tocilizumab
Introduction to Tocilizumab
Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). It was developed by Roche and Chugai and first approved by the FDA in 2010. Tocilizumab is used to treat various inflammatory conditions in both adults and children, making it a crucial medication in rheumatology and, more recently, in the management of severe COVID-19.
Mechanism of Action
Tocilizumab works by binding to both soluble and membrane-bound interleukin-6 receptors (sIL-6R and mIL-6R), inhibiting IL-6-mediated signaling. IL-6 is a pleiotropic pro-inflammatory cytokine involved in diverse physiological processes including T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute-phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. By blocking IL-6 signaling, tocilizumab reduces inflammation and modifies the immune response in various inflammatory conditions.
Indications
Tocilizumab is FDA-approved for:
- Rheumatoid Arthritis (RA) in adults
- Giant Cell Arteritis (GCA) in adults
- Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD) in adults
- Polyarticular Juvenile Idiopathic Arthritis (PJIA) in patients 2 years of age and older
- Systemic Juvenile Idiopathic Arthritis (SJIA) in patients 2 years of age and older
- Cytokine Release Syndrome (CRS) induced by CAR T-cell therapy in patients 2 years of age and older
- COVID-19 in hospitalized adults receiving systemic corticosteroids and requiring supplemental oxygen or mechanical ventilation
Administration
Tocilizumab can be administered intravenously (IV) or subcutaneously (SC), depending on the indication:
- IV administration:
- RA, GCA, SSc-ILD: 4-8 mg/kg every 4 weeks
- PJIA, SJIA: 8-12 mg/kg every 2-4 weeks (weight-based)
- CRS: 8 mg/kg (12 mg/kg for patients <30 kg)
- COVID-19: 8 mg/kg (max 800 mg), may repeat once after 8-24 hours if needed
- SC administration (RA, GCA, SSc-ILD):
- Weight ≥100 kg: 162 mg every week
- Weight <100 kg: 162 mg every other week, may increase to every week based on clinical response
Efficacy and Safety
Efficacy:
- In RA: Significant improvement in disease activity, physical function, and inhibition of structural joint damage
- In GCA: Sustained remission and reduced steroid use
- In PJIA and SJIA: Improved joint symptoms and systemic features
- In CRS: Rapid reversal of symptoms in most patients
- In COVID-19: Reduced progression to mechanical ventilation or death in selected patients
Safety:
- Common adverse effects: Upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT
- Serious adverse effects: Serious infections, gastrointestinal perforations, anaphylaxis, hepatotoxicity
- Laboratory abnormalities: Neutropenia, thrombocytopenia, elevated liver enzymes, increased lipid levels
Pediatric Use
Tocilizumab has several approved indications in pediatric patients:
- PJIA: Approved for patients 2 years of age and older
- SJIA: Approved for patients 2 years of age and older
- CRS: Approved for patients 2 years of age and older
Key considerations for pediatric use:
- Dosing is weight-based in children
- Regular monitoring of growth and development is recommended
- Particular attention should be paid to vaccination status, as live vaccines should be avoided during treatment
- Long-term safety data in children is still being collected, emphasizing the need for ongoing vigilance
Special Considerations
- Infections: Serious and sometimes fatal infections have been reported. Screen for latent tuberculosis before starting tocilizumab.
- Vaccinations: Avoid live vaccines during treatment. Update vaccinations prior to initiating therapy.
- Laboratory Monitoring: Regularly monitor neutrophils, platelets, ALT/AST, and lipids.
- Pregnancy: Limited data available. Use during pregnancy only if potential benefit justifies potential risk to the fetus.
- Breastfeeding: Tocilizumab has been detected in human milk. Consider developmental and health benefits of breastfeeding along with mother's clinical need for tocilizumab.
- Drug Interactions: May decrease the formation of CYP450 enzymes. Upon initiation or discontinuation, monitor patients taking drugs metabolized by these enzymes.
- Macrophage Activation Syndrome (MAS): Remains a risk in SJIA patients treated with tocilizumab. Monitor for signs and symptoms of MAS.
