TNF Inhibitor

Aka: TNF Inhibitor, Anti-TNF Agent, Tumor Necrosis Factor Inhibitor, TNF-a blocker, Tumor Necrosis Factor Alpha Inhibitor

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II. Indications: Autoimmune Conditions

  1. FDA Approved
    1. Rheumatoid Arthriitis
    2. Juvenile polyarticular Rheumatoid Arthritis
    3. Spondyloarthropathy (e.g. Ankylosing Spondylitis)
    4. Inflammatory Bowel Disease (Crohns Disease, Ulcerative Colitis)
    5. Psoriasis
    6. Psoriatic Arthritis
  2. Off-Label
    1. Sarcoidosis
    2. Hidradenitis suppuritiva
    3. Adamantiades-Behcet's Disease
    4. Pyoderma Gangrenosum
    5. Dermatomyositis
    6. Scleroderma
    7. Noninfectious Uveitis

III. Contraindications: Relative (Consult before use)

  1. Congestive Heart Failure (NYHA Class 3 to 4)
  2. Recurrent Bacterial or Viral Infection
  3. Latent Infections (e.g. Tuberculosis, Histoplasmosis, Coccidioidomycosis)
  4. HIV Infection
  5. Hepatitis B
  6. Hepatitis C
  7. Organ Transplant on Immunosuppression
  8. Active Cancer
  9. Demyelinating Disease (e.g. Multiple Sclerosis)
  10. Pregnancy
    1. Most TNF Inhibitors may be used in pregnancy if risk outweighs benefit
    2. Some TNF Inhibitors are monitored with pregnancy registries
  11. Concurrent use of other Monoclonal Antibody

IV. Mechanism

  1. Tumor Necrosis Factor Inhibitors
    1. Primarily monoclonal antibodies that block TNF from binding cell receptors
    2. Symptomatic response is typically within 2 to 4 weeks of dosing
  2. Tumor Necrosis Factor (TNF)
    1. Cell surface Proteins involved in Lymphocyte homeostasis
    2. Originally identified by their ability to necrose tumor cells
    3. TNF-a is only 30% homologous with TNF-b, but they share 2 receptors
  3. Tumor Necrosis Factor Alpha (TNF-a)
    1. Serum Glycoprotein synthesized by activated Macrophages and mononuclear Leukocytes
    2. Necrotizing activity against tumor cell lines
  4. Tumor Necrosis Factor Beta (TNF-b)
    1. Soluble Protein released by activated Lymphocytes (on Antigen binding or by T-Cell mitogens)
    2. TNF-b is cytotoxic to targeted cells and triggered in allergic and inflammatory conditions

V. Precautions

  1. TNF Inhibitors predispose to serious infections and malignancy
  2. Prepare for TNF Inhibitor use with infection screening (e.g. Tuberculosis) and Immunizations
    1. See Monoclonal Antibody

VI. Medications

  1. Older xTNF agents included Thalidomide
  2. Modern xTNF agents (in 2016) are primarily monoclonal antibodies
    1. Adalimumab (Humira)
    2. Certolizumab (Cimzia)
    3. Golimumab (Simponi)
    4. Infliximab (Remicade)
  3. Fusion Protein (recombinant TNF Receptor fused to IgG Fc domain)
    1. Etanercept (Enbrel)

VII. Complications

  1. Skin Cancer
    1. Melanoma
    2. Nonmelanoma Skin Cancer
  2. Lymphoma
    1. Lymphoma
      1. More case reports in children and teens
      2. Non-hodgkins Lymphoma has also been reported in older adults on TNF agents
    2. Hepatosplenic T Cell Lymphoma
      1. Reported in children with Inflammatory Bowel Disease on TNF agents
    3. Dahmus (2020) Clin Exp Gastroenterol 13:339-350 +PMID: 32982364 [PubMed]
  3. Congestive Heart Failure (Infliximab)
    1. Behnam (2005) Skinmed 4(6):363-8 +PMID:16276152 [PubMed]
  4. Multiple Sclerosis
    1. Kemanetzoglou (2017) Curr Neurol Neurosci Rep 17(4): 36 +PMID: 28337644 [PubMed]
  5. Opportunistic Infection or reactivated infections
    1. Tuberculosis
      1. Screen for latent infection prior to initiating TNF agent
    2. Disseminated Histoplasmosis
    3. Coccidioidomycosis
    4. Blastomycosis
    5. Hepatitis B (reactivation)
    6. Cytomegalovirus
    7. Leishmaniasis
  6. References
    1. Toussi (2013) Clin Infect Dis 57:1318–30 +PMID:23899685 [PubMed]

VIII. Prevention

  1. Update Vaccinations prior to starting therapy
    1. Live Vaccines may not be used concurrently with xTNF agents
  2. Screen for Tuberculosis and other infections prior to starting xTNF-a agents
  3. Requires regular lab monitoring depending on agent and condition being treated
  4. Skin Cancer Prevention with regular use of Sunscreen and Self Skin Exam
  5. Patients should seek medical evaluation for acute infectious symptoms while on xTNF agents

IX. References

  1. (2018) Presc Lett 25(7): 40

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