Tumor Necrosis Factor Inhibitor

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Contents 1 More Specific Terms 2 Introduction 3 Indications 4 Contraindications 5 Adverse-effects 6 Mechanism-of-action 7 More General Terms 8 Additional Terms 9 References

More Specific Terms

• adalimumab (Humira)
• certolizumab (Cimzia)
• etanercept (Enbrel)
• golimumab (Simponi)
• infliximab (Remicade)

Introduction

• Includes:

• infliximab ( Remicade)
• etanercept ( Enbrel)
• adalimumab ( Humira)
• certolizumab ( Cimzia)
• golimumab ( Simponi)

Indications

• connective tissue disorders including rheumatoid arthritis
• spondyloarthropathies

Contraindications

• active infection
• concurrent use of other biologic agent ( abatacept, rituximab, anakinra)

• Caution: PPD prior to initiation of therapy

Adverse-effects

• 2-fold increased risk of infections [5]

• increased risk of soft tissue & skin infection
• increased risk of intracellular bacterial infection

• tuberculosis (increased risk of reactivation TB)
• Listeria [7]
• Salmonella ?
• Legionella [7]

• pulmonary & disseminated histoplasmosis, coccidioidomycosis, blastomycosis & other opportunistic infections are not consistently recognized in patients taking TNF- alpha blockers; this has resulted in delays in appropriate treatment, & death; empiric antifungal treatment indicated for suspected disseminated mycosis in patients taking TNF-alpha blocker
• increased risk of cancer

• increased risk of lymphoma & other cancers associated with use in children & adolescents [3]
• not associated with an increase in overall cancer risk [6]
• higher risk of lymphoma risk than the general population, but not higher than those taking traditional DMARDs
• increased risk for nonmelanoma skin cancer

• drug-induced lupus [4]
  
• drug adverse effects of immunosuppressive agents
• drug adverse effects of tumor necrosis factor (TNF) inhibitors

Mechanism-of-action

• TNF-alpha inhibition

More General Terms

• immunosuppressive agent
• disease-modifying antirheumatic agent (DMARD)

Additional Terms

• tumor necrosis factor ligand superfamily member 2, tumor necrosis factor [TNF]-alpha or cachectin

References

1. Dixon WG et al, Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy. Arthritis Rheum 2006, 54:2368 PMID: [1]
   - Mohan AK, Cote TR, Block JA, Manadan AM, Siegel JN, Braun MM. Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor. Clin Infect Dis. 2004 Aug 1;39(3):295-9. Epub 2004 Jul 16. PMID: [2]
   - Costamagna P et al, tuyberculosis associated with blocking agents against tumor necrosis factor-alpha - California, 2002-2003, MMWR Morb Mortal Wkly Rep 2004, Aug 6; 53:683-86
   - Keane J. Tumor necrosis factor blockers and reactivation of latent tuberculosis. Clin Infect Dis. 2004 Aug 1;39(3):300-2. Epub 2004 Jul 16. No abstract available. PMID: [3]
2. FDA MedWatch [4]
3. FDA MedWatch Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi) August 2009 [5]
4. Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
5. Komano Y et al. Incidence and risk factors for serious infection in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: A report from the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety. J Rheumatol 2011 Jul; 38:1258. PMID: [6]
6. Mariette X et al Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis Ann Rheum Dis doi:10.1136/ard.2010.149419 <PubMed> PMID: [7] <Internet> [8]
7. FDA MedWatch 09-09-11 Tumor Necrosis Factor-alpha (TNF-alpha) Blockers: Label Change - Boxed Warning Updated for Risk of Infection from Legionella and Listeria including Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol), and Simponi (golimumab) [9]
8. Grijalva CG et al Initiation of tumor necrosis factor-alpha antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA 2011 Nov 6 <PubMed> PMID: [10] <Internet> [11]
   - Dixon W and Felson DT. Is anti-TNF therapy safer than previously thought? JAMA 2011 Nov 6 <PubMed> PMID: [12] <Internet> [13]

tumor necrosis factor (TNF) inhibitor