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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Related Studies

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Definition (NCI) A human-mouse chimeric antibody, constructed from a murine anti-interleukin 6 (IL-6) monoclonal antibody, with antitumor and anti-inflammatory activities. Containing the antigen-binding variable region of the murine antibody, CLB-IL-6-8, and the constant region of a human IgG1kappa immunoglobulin, anti-IL-6 chimeric monoclonal antibody has high affinity for recombinant as well as native IL-6 and inhibits the binding of IL-6 to the IL-6 receptor (IL-6R), resulting in the blockade of the IL-6/IL-6R/gp130 signal transduction pathway, and, subsequently, antitumor and anti-inflammatory activities.
Definition (NCI_NCI-GLOSS) A chimeric (made from human and mouse proteins) monoclonal antibody being studied in the treatment of advanced kidney cancer and other types of cancer. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Anti-IL-6 chimeric monoclonal antibody works by blocking inflammation and tumor growth.
Definition (PDQ) A human-mouse chimeric antibody, constructed from a murine antiinterleukin 6 (IL-6) monoclonal antibody, with antitumor and antiinflammatory activities. Containing the antigen-binding variable region of the murine antibody, CLB-IL-6-8, and the constant region of a human IgG1kappa immunoglobulin, anti-IL-6 chimeric monoclonal antibody has high affinity for recombinant as well as native IL-6 and inhibits the binding of IL-6 to the IL-6 receptor (IL-6R), resulting in the blockade of the IL-6/IL-6R/gp130 signal transduction pathway, and, subsequently, antitumor and antiinflammatory activities. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=475765&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=475765&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61084" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSH C504234
English anti-IL-6 chimeric monoclonal antibody, Anti-IL-6 Chimeric Monoclonal Antibody, Siltuximab, siltuximab, SILTUXIMAB

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English Anti-Interleukin 6 Monoclonal Antibody ALD518, Anti-IL6 Monoclonal Antibody ALD518

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