Interleukin-6 Receptor Antagonist

Aka: Interleukin-6 Receptor Antagonist, Anti-IL6 Monoclonal Antibody, Sarilumab, Kevzara, Siltuximab, Sylvant

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II. Indications

  1. 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)
  2. Multicentric Castleman’s disease (Siltuximab)
  3. Rheumatologic Conditions (Tocilizumab)
    1. Rheumatoid Arthritis (refractory, moderate to severe)
    2. Giant Cell Arteritis
    3. Polyarticular Juvenile Idiopathic Arthritis
    4. Systemic Juvenile Idiopathic Arthritis

III. Mechanism

  1. Interleukin-6 (IL-6)
    1. Pro-inflammatory Cytokine synthesized and release by immune cells
  2. 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

IV. Medications

  1. Tocilizumab
    1. See Tocilizumab
  2. Sarilumab (Kevzara)
    1. Rheumatoid Arthritis: 200 mg SQ every 2 weeks
    2. Risk of Neutropenia, Thrombocytopenia, Liver Function Test abnormalities
    3. Store in refrigerator (may be at room Temperature for up to 14 days)
  3. Siltuximab (Sylvant)
    1. Multicentric Castleman’s disease: 11 mg/kg IV overy 1 hour every 3 weeks
    2. Risk of severe infusion reactions including Anaphylaxis

V. Adverse Effects

  1. Severe infections (esp. opportunistic Viral Infections, Bacterial Infections, invasive fungal infections)
  2. Severe infusion reactions including Anaphylaxis (Siltuximab)
  3. Reactivated Herpes Zoster
  4. Reactivated Tuberculosis
  5. Neutropenia
    1. Avoid if Absolute Neutrophil Count (ANC) <2000 (Sarilumab, Tocilizumab), or <1000 (Siltuximab)
  6. Thrombocytopenia
    1. Avoid if Platelet Count <150,000 (Sarilumab), <100,000 (Tocilizumab) or <75,000 (Siltuximab)
  7. Increased liver enzymes (AST, ALT)
    1. Do not start if serum transaminases are >1.5 times normal
    2. Stop if serum transaminases are >5 times normal
  8. Hyperlipidemia
  9. GI perforation
    1. Higher risk in Rheumatoid Arthritis patients with a history of Diverticulitis

VI. Safety

  1. Unknown safety in pregnancy
  2. Unknown safety in Lactation
  3. Monitoring (obtain labs after 4-8 weeks and then every 3 months)
    1. Complete Blood Count (Neutrophils, Platelets)
    2. Serum transaminases (AST, ALT)
    3. Lipid Panel

VII. Drug Interactions

  1. Live Vaccines
    1. Hold for 1 dosing interval before and 4 weeks after Live Vaccines

VIII. References

  1. Kamer and LoVecchio (2020) Crit Dec Emerg Med 34(8): 24

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