II. Indications
- Severe Cytokine Release Syndrome (CRS)
- CAR T-Cell Therapy Related CRS (FDA approved use of Tocilizumab)
- COVID-19 related CRS (experimental Tocilizumab use in 2020)
-
Rheumatologic Conditions
- Rheumatoid Arthritis (refractory, moderate to severe)
- Giant Cell Arteritis
- Polyarticular Juvenile Idiopathic Arthritis
- Systemic Juvenile Idiopathic Arthritis
III. Contraindications
- Live Vaccines
- Active liver disease or hepatic dysfunction
IV. Mechanism
- See Interleukin-6 Receptor Antagonist
-
Interleukin-6 (IL-6)
- Pro-inflammatory Cytokine synthesized and release by immune cells
-
Interleukin-6 Receptor Antagonist
- Monoclonal antibodies bind and block IL-6
- Blockade of of IL-6 decreases production of proinflammatory Cytokines and acute phase reactants
V. Medications
- Intravenous solution for injection (single dose vials 20 mg/ml): 80 mg, 200 mg and 400 mg
- Subcutaneous prefilled syringes or ACTPen Autoinjector (162 mg/0.9 ml)
- Keep refrigerated
- Allow to warm to room Temperature for 30 minutes before injection (reduces pain)
VI. Dosing: Adult
-
Rheumatoid Arthritis
- Subcutaneous (SQ)
- Start 162 mg SQ every 2 weeks (every 1 week if weight >100 kg)
- May be titrated to weekly dosing if needed
- Intravenous (IV)
- Start 4 mg/kg IV every 4 weeks
- May increase to 8 mg/kg (up to 800 mg) IV every 4 weeks
- Subcutaneous (SQ)
-
Giant Cell Arteritis
- Subcutaneous (SQ)
- Start 162 mg SQ every week (may be given every 2 weeks if needed)
- Combined with Corticosteroid
- Subcutaneous (SQ)
-
Cytokine Release Syndrome (CAR T-Cell Therapy Related)
- Intravenous: 8 mg/kg (up to 800 mg) IV (or for <30 kg, use 12 mg/kg)
- May repeat every 8 hours for up to 3 doses if no initial response
VII. Dosing: Child (age >=2 years)
- FDA Approved for age >=2 years
- Polyarticular Juvenile Idiopathic Arthritis
- Subcutaneous (SQ)
- Weight <30 kg: 162 mg SQ every 3 weeks
- Weight >=30 kg: 162 mg SQ every 2 weeks
- Intravenous (IV)
- Weight <30 kg: 10 mg/kg IV every 4 weeks
- Weight >=30 kg: 8 mg/kg IV every 4 weeks
- Subcutaneous (SQ)
- Systemic Juvenile Idiopathic Arthritis
- Subcutaneous (SQ)
- Weight <30 kg: 162 mg SQ every 2 weeks
- Weight >=30 kg: 162 mg SQ every 1 week
- Intravenous (IV)
- Weight <30 kg: 12 mg/kg IV every 2 weeks
- Weight >=30 kg: 8 mg/kg IV every 2 weeks
- Subcutaneous (SQ)
-
Cytokine Release Syndrome (CAR T-Cell Therapy Related)
- Intravenous (IV)
- Weight <30 kg: 12 mg/kg IV once
- Weight >=30 kg: 8 mg/kg (up to 800 mg) IV once
- May repeat every 8 hours for up to 3 doses if no initial response
- Intravenous (IV)
VIII. Adverse Effects
- Severe infections (esp. opportunistic Viral Infections, Bacterial Infections, invasive fungal infections)
- Reactivated Herpes Zoster
- Reactivated Tuberculosis
-
Neutropenia
- Avoid if Absolute Neutrophil Count (ANC) <2000
-
Thrombocytopenia
- Avoid if Platelet Count <100,000
- Increased liver enzymes (AST, ALT)
- Avoid starting if serum transaminases are >1.5 times normal
- Stop if serum transaminases increase >5 times normal
- Hyperlipidemia
- GI perforation
- Higher risk in Rheumatoid Arthritis patients with a history of Diverticulitis
IX. Safety
- Unknown safety in pregnancy
- Fetal exposure increases after 20 weeks gestation
- Unknown safety in Lactation
- Monitoring
- Timing
- Adults: Labs after 4-8 weeks and then every 3 months
- Children: Monitoring intervals vary by indication (see other references)
- Complete Blood Count (Neutrophils, Platelets)
- Serum transaminases (AST, ALT)
- Lipid panel
- Infection signs
- Timing
X. Drug Interactions
XI. Resources
XII. References
- Kamer and LoVecchio (2020) Crit Dec Emerg Med 34(8): 24