Anti-Tumor Necrosis Factor-α Therapy (Anti-TNF-α Therapy)

Indications


Anti-Tumor Necrosis Factor-α (Anti-TNFα) Agents

  • Adalimumab (Humira) (see Adalimumab, [[Adalimumab]])
    • Mechanism: binds to circulating and membrane-bound TNFα
    • Administration: SQ
  • Certolizumab Pegol (Cimzia) (see Certolizumab Pegol, [[Certolizumab Pegol]])
    • Mechanism: pegylated humanized antibody Fab fragment of TNFα monoclonal antibody -> binds to and selectively neutralizes human TNFα
    • Administration: SQ
  • Etanercept (Enbrel) (see Etanercept, [[Etanercept]])
    • Mechanism: binds to circulating TNFα
    • Administration: SQ
  • Golimumab (Simponi, Simponi Aria) (see Golimumab, [[Golimumab]])
    • Mechanism: human monoclonal antibody against TNFα
    • Administration: SQ
  • Infliximab (Remicade) (see Infliximab, [[Infliximab]])
    • Mechanism: binds to circulating and membrane-bound TNFα
    • Administration: IV

Pharmacology

Physiology of TNFα

  • TNFα is a cytokine which has been implicated in the inflammatory cascades of multiple diseases, including rheumatoid arthritis, psoriasis-associated arthritis, ankylosing spondylitis, and inflammatory bowel disease

General Adverse Effects of Anti-Tumor Necrosis Factor-α (Anti-TNFα) Therapy

Dermatologic Adverse Effects

Erythema Multiforme (see Erythema Multiforme, [[Erythema Multiforme]])

  • xxx

Infectious Adverse Effects

  • Aspergillus (see Aspergillus, [[Aspergillus]])
    • Invasive Pulmonary Aspergillosis (see Aspergillus, [[Aspergillus]])
  • Blastomyces (see Blastomycosis, [[Blastomycosis]]): case report of 3 cases
  • Candida (see Candida, [[Candida]])
    • Candida Esophagitis
    • Candidemia
    • Oropharyngeal Thrush
  • Coccidioides Immitis (see Coccidioidomycosis, [[Coccidioidomycosis]])
  • Cryptococcus (see Cryptococcosis, [[Cryptococcosis]]): 28 published cases
  • Histoplasma (see Histoplasmosis, [[Histoplasmosis]])
  • Legionella (see Legionellosis, [[Legionellosis]]): case series of 10 patients
  • Listeriosis (see Listeriosis, [[Listeriosis]]): case series of 15 patients
  • Mycobacterium Tuberculosis (see Tuberculosis, [[Tuberculosis]])
  • Pneumocystis Jirovecii (see Pneumocystis Jirovecii, [[Pneumocystis Jirovecii]])
  • Strongyloides (see Strongyloidiasis, [[Strongyloidiasis]]): 1 case report
  • Viral Upper Respiratory Infections (however, there is no increased risk of viral pneumonias)

Pulmonary Adverse Effects

Accelerated Progression of Rheumatoid Lung Nodules (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])

  • Epidemiology
    • Etanercept (Enbrel) (see Etanercept, [[Etanercept]]): may accelerate progression of rheumatoid lung nodules

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

  • Epidemiology
    • Infliximab (Remicade) (see Infliximab, [[Infliximab]])

Granulomatous Lung Disease (see Granulomatous Lung Disease, [[Granulomatous Lung Disease]])

  • Epidemiology
    • Etanercept (Enbrel) (see Etanercept, [[Etanercept]]): can cause a pneumonitis with non-necrotizing granulomas and lymphohistiocytic infiltrates
    • Infliximab (Remicade) (see Infliximab, [[Infliximab]]): can cause a pulmonary “bronchiocentric allergic granulomatosis” (observed in a patient with ankylosing spondylitis)

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease, [[Interstitial Lung Disease]])

  • Epidemiology
    • Etanercept (Enbrel) (see Etanercept, [[Etanercept]]): may worsen pre-existing RA-associated interstitial lung disease
    • Infliximab (Remicade) (see Infliximab, [[Infliximab]])
      • May worsen pre-existing RA-associated interstitial lung disease
      • Addition of infliximab can precipitate methotrexate pneumonitis (see Methotrexate, [[Methotrexate]])
    • Adalimumab (Humira) (see Adalimumab, [[Adalimumab]]): interstitial lung disease has been reported

Pulmonary Infiltrates with Eosinophilia (see Drug-Induced Pulmonary Eosinophilia, [[Drug-Induced Pulmonary Eosinophilia]])

  • Epidemiology
    • Infliximab (Remicade) (see Infliximab, [[Infliximab]])

Renal Adverse Effetcs

Acute Interstitial Nephritis (see Acute Interstitial Nephritis, [[Acute Interstitial Nephritis]])

  • Epidemiology: associated with etanercept

Rheumatologic Adverse Effects

Accelerated Progression of Rheumatoid Lung Nodules (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])

  • Epidemiology
    • Etanercept (Enbrel) (see Etanercept, [[Etanercept]]): may accelerate progression of rheumatoid lung nodules

Drug-Induced Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])

  • Epidemiology
    • Adalimumab (Humira) (see Adalimumab, [[Adalimumab]])
    • Etanercept (Enbrel) (see Etanercept, [[Etanercept]])
    • Infliximab (Remicade) (see Infliximab, [[Infliximab]])

References

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  • Infliximab (chimeric anti-tumor necrosis factor-alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet 1999; 354:1932-1939
  • Tumor necrosis factor alpha antibody (infliximab) therapy profoundly downregulates the inflammation in Crohn’s ileocolitis. Gastroenterology 1999; 116:22-28
  • Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345:1098-1104
  • Cell-mediated immunity to Histoplasma capsulatum. Semin Respir Infect 2001; 16:102-108
  • Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor-alpha
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  • Effects of infliximab on apoptosis and reverse signaling of monocytes from healthy individuals and patients with Crohn’s disease. Inflamm Bowel Dis 2004; 10:801-810
  • Pneumocystis carinii pneumonia with oral candidiasis after infliximab therapy for Crohn’s disease. Dig Dis Sci 2004; 1458- 1460
  • Fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in patients given infliximab. BMJ 2004; 329:1266
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  • Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis. J Rheumatol 2006; 33:622-628
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  • Development of active tuberculosis following initiation of infliximab despite appropriate prophylaxis. Rheumatology (Oxford) 2007; 46:887-888
  • Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of 84 cases. Dig Dis Sci 2007; 52:1481-1484
  • Pneumocystis carinii pneumonia in a patient on etanercept for psoriatic arthritis. Ir J Med Sci 2007; 176:309-311
  • Pneumocystis carinii pneumonia in a rheumatoid arthritis patient treated with adalimumab. Scand J Infect Dis 2007; 39:475-478
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