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drug adverse effects of tumor necrosis factor (TNF) inhibitors

Adverse effects: 1) pancytopenia [2] 2) 2-fold increased risk of infections [3] a) increased risk of soft tissue & skin infection b) increased risk of intracellular bacterial infection 1] tuberculosis (increased risk of reactivation TB) [6] 2] Listeria monocytogenes (non-bloody diarrhea, encephalitis, dairy) [5] 3] Salmonella ? 4] Legionella [5] 3) 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 4) increased risk of cancer a) increased risk of lymphoma & other cancers associated with use in children & adolescents [1] b) not associated with an increase in overall cancer risk [4] c) higher risk of lymphoma risk than the general population, but not higher than those taking traditional DMARDs d) increased risk for nonmelanoma skin cancer e) low risk of cancers [8] 5) drug-induced lupus [2] 6) cutaneous reactions common [7] - psoriasiform dermatitis (most common) [9] - cutaneous autoimmune disease - subacute cutaneous lupus erythematosus [2] - referral to a dermatologist can help keep patients ontreatment [9] 7) heart failure [2] 8) demyelinating disorders [2] 9) increased risk of inflammatory CNS diseases, especially demyelinating diseases [12] 10) use in 3rd trimester for inflammatory bowel disease not associated with adverse birth outcomes [10]

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GENERAL: drug adverse effect(s) of DRUGS: tumor necrosis factor inhibitor FORM: drug adverse effects tumor necrosis factor inhibitor

References

  1. FDA MedWatch Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi) August 2009 http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm175843.htm
  2. Medical Knowledge Self Assessment Program (MKSAP) 14, 18. American College of Physicians, Philadelphia 2006, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. 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: 21498482
  4. 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 PMID: 21885875 http://ard.bmj.com/content/early/2011/07/29/ard.2010.149419.abstract
  5. 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) http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm270977.htm
  6. 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: 16868999 - 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: 15306993 - 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: 15306994 - Singh JA et al Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis. Lancet. May 11, 2015 PMID: 25975452 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961704-9/abstract - Dixon WG. Rheumatoid arthritis: Biological drugs and risk of infection. Lancet 2015 May 11 PMID: 25975453 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961907-3/abstract
  7. Hernandez MV et al. Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: Study using the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases. Arthritis Care Res (Hoboken) 2013 Dec; 65:2024 PMID: 23926075
  8. Andersen NN et al. Association between tumor necrosis factor- alpha antagonists and risk of cancer in patients with inflammatory bowel disease. JAMA 2014 Jun 18; 311:2406 PMID: 24938563
  9. Cleynen I et al Characteristics of Skin Lesions Associated With Anti-Tumor Necrosis Factor Therapy in Patients With Inflammatory Bowel Disease: A Cohort Study. Ann Intern Med. Published online 8 December 2015 PMID: 26641955 http://annals.org/article.aspx?articleid=2474360
  10. Bachert A Anti-TNF Therapy Seems Safe in Pregnant Women with IBD. - Use in third trimester not tied to adverse birth outcomes. MedPage Today Dec 11, 2016 http://www.medpagetoday.com/MeetingCoverage/AIBD/61998
  11. Centers for Disease Control and Prevention (CDC). Tuberculosis associated with blocking agents against tumor necrosis factor-alpha--California, 2002-2003. MMWR Morb Mortal Wkly Rep 2004 Aug 6; 53:683. PMID: 15295313 Free full text
  12. Xie W, Sun Y, Zhang W, Zhu N, Xiao S et al Risk of Inflammatory Central Nervous System Diseases After Tumor Necrosis Factor-Inhibitor Treatment for Autoimmune Diseases: A Systematic Review and Meta-Analysis. JAMA Neurol. 2024 Oct 21. PMID: 39432288