Tocilizumab

Severe Cytokine Release Syndrome (CRS)
1. CAR T-Cell Therapy Related CRS (FDA approved use of Tocilizumab)
2. COVID-19 related CRS (experimental Tocilizumab use in 2020)
Rheumatologic Conditions
1. Rheumatoid Arthritis (refractory, moderate to severe)
2. Giant Cell Arteritis
3. Polyarticular Juvenile Idiopathic Arthritis
4. Systemic Juvenile Idiopathic Arthritis

See Interleukin-6 Receptor Antagonist
Interleukin-6 (IL-6)
1. Pro-inflammatory Cytokine synthesized and release by immune cells
Interleukin-6 Receptor Antagonist
1. Monoclonal antibodies bind and block IL-6
2. Blockade of of IL-6 decreases production of proinflammatory Cytokines and acute phase reactants

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)
1. Keep refrigerated
2. Allow to warm to room Temperature for 30 minutes before injection (reduces pain)

Rheumatoid Arthritis
1. Subcutaneous (SQ)
  1. Start 162 mg SQ every 2 weeks (every 1 week if weight >100 kg)
  2. May be titrated to weekly dosing if needed
2. Intravenous (IV)
  1. Start 4 mg/kg IV every 4 weeks
  2. May increase to 8 mg/kg (up to 800 mg) IV every 4 weeks
Giant Cell Arteritis
1. Subcutaneous (SQ)
  1. Start 162 mg SQ every week (may be given every 2 weeks if needed)
  2. Combined with Corticosteroid
Cytokine Release Syndrome (CAR T-Cell Therapy Related)
1. Intravenous: 8 mg/kg (up to 800 mg) IV (or for <30 kg, use 12 mg/kg)
2. May repeat every 8 hours for up to 3 doses if no initial response

FDA Approved for age >=2 years
Polyarticular Juvenile Idiopathic Arthritis
1. Subcutaneous (SQ)
  1. Weight <30 kg: 162 mg SQ every 3 weeks
  2. Weight >=30 kg: 162 mg SQ every 2 weeks
2. Intravenous (IV)
  1. Weight <30 kg: 10 mg/kg IV every 4 weeks
  2. Weight >=30 kg: 8 mg/kg IV every 4 weeks
Systemic Juvenile Idiopathic Arthritis
1. Subcutaneous (SQ)
  1. Weight <30 kg: 162 mg SQ every 2 weeks
  2. Weight >=30 kg: 162 mg SQ every 1 week
2. Intravenous (IV)
  1. Weight <30 kg: 12 mg/kg IV every 2 weeks
  2. Weight >=30 kg: 8 mg/kg IV every 2 weeks
Cytokine Release Syndrome (CAR T-Cell Therapy Related)
1. Intravenous (IV)
  1. Weight <30 kg: 12 mg/kg IV once
  2. Weight >=30 kg: 8 mg/kg (up to 800 mg) IV once
  3. May repeat every 8 hours for up to 3 doses if no initial response

Severe infections (esp. opportunistic Viral Infections, Bacterial Infections, invasive fungal infections)
Reactivated Herpes Zoster
Reactivated Tuberculosis
Neutropenia
1. Avoid if Absolute Neutrophil Count (ANC) <2000
Thrombocytopenia
1. Avoid if Platelet Count <100,000
Increased liver enzymes (AST, ALT)
1. Avoid starting if serum transaminases are >1.5 times normal
2. Stop if serum transaminases increase >5 times normal
Hyperlipidemia
GI perforation
1. Higher risk in Rheumatoid Arthritis patients with a history of Diverticulitis

Unknown safety in pregnancy
1. Fetal exposure increases after 20 weeks gestation
Unknown safety in Lactation
Monitoring
1. Timing
  1. Adults: Labs after 4-8 weeks and then every 3 months
  2. Children: Monitoring intervals vary by indication (see other references)
2. Complete Blood Count (Neutrophils, Platelets)
3. Serum transaminases (AST, ALT)
4. Lipid panel
5. Infection signs

Broad effects on multiple CYP450 enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4)
May affect drug levels of agents with a narrow therapeutic range