tumor necrosis factor (TNF) inhibitor
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Introduction
Includes:
- infliximab (Remicade)
- etanercept (Enbrel)
- adalimumab (Humira)
- certolizumab (Cimzia)
- golimumab (Simponi)
Indications
- autoimmune disease or connective tissue disorders
- rheumatoid arthritis
- spondyloarthropathies
- inflammatory bowel disease (IBD) (ulcerative colitis, Crohn's disease)
- reduce risk of Parkinson disease in patients with IBD[20]
- poriasis
- may mitigate risk for Alzheimer's disese in inflammatory disorders[22]
Contraindications
- concurrent use of other biologic agent (abatacept, rituximab, anakinra)
- active infection
Caution: screening for tuberculosis, hepatitis B & hepatitis C prior to initiation of therapy[4]
* treatment of active or latent tuberculosis prior to administration of TNF-alpha inhibitor
* if patient develops signs & symptoms of tuberculosis while on a TNF-alpha inhibitor, obtain induced sputum acid-fast bacilli & culture (bronchoscopy & bronchoalveolar lavage is too invasive)[22]
- use in 3rd trimester for inflammatory bowel disease not associated with adverse birth outcomes[18]
Adverse effects
- pancytopenia
- 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 & death from disseminated disease[4]
- Listeria[7]
- Salmonella ?
- Legionella[7]
- tuberculosis
- increased risk of Herpes zoster
- 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 <A146370>TNF-alpha</A146370> 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
- increased risk of melanoma in patients with rheumatoid arthritis (RR=1.5)[10]
- low risk of cancers[15]
- TNF inhibitors do not increase risk of cancer recurrence in cancer survivors[21]
- autoantibodies
- ANA, anti-dsDNA Ab, anti-Sm Ab common
- drug-induced lupus uncommon[4]
- cutaneous reactions common[14][17]
- psoriasiform dermatitis (most common)[17]
- cutaneous autoimmune disease
- referral to a dermatologist can help keep patients on treatment[17]
- heart failure[4]
- demyelinating disorders[4]
- increased risk of inflammatory CNS diseases, especially demyelinating diseases[23]
- drug adverse effects of immunosuppressive agents
- drug adverse effects of tumor necrosis factor (TNF) inhibitors
- drug adverse effects of biologic immunosuppressive agents
Mechanism of action
- TNF-alpha inhibition
More general terms
More specific terms
- adalimumab (Humira, Idacio, Yusimry, Yuflyma)
- certolizumab pegol (Cimzia)
- etanercept (Enbrel)
- golimumab (Simponi)
- infliximab (Remicade)
Additional terms
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25975452 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25975453 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961907-3/abstract - ↑ FDA MedWatch http://www.fda.gov/medwatch/safety/2008/safety08.htm#TNF2
- ↑ 3.0 3.1 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
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Medical Knowledge Self Assessment Program (MKSAP) 14, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21498482
- ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/21885875 <Internet> http://ard.bmj.com/content/early/2011/07/29/ard.2010.149419.abstract
- ↑ 7.0 7.1 7.2 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
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/22056398 <Internet> http://jama.ama-assn.org/content/306/21/2331
Dixon W and Felson DT. Is anti-TNF therapy safer than previously thought? JAMA 2011 Nov 6 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22056396 <Internet> http://jama.ama-assn.org/content/306/21/2380 - ↑ 9.0 9.1 Winthrop KL et al Association Between the Initiation of Anti-Tumor Necrosis Factor Therapy and the Risk of Herpes Zoster. JAMA. 2013;309(9):887-895 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23462785 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1660380
- ↑ 10.0 10.1 Raaschou P et al. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: Nationwide population based prospective cohort study from Sweden. BMJ 2013 Apr 8; 346:f1939 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23568792
- ↑ Costa MF, Said NR, Zimmermann B. Drug-induced lupus due to anti-tumor necrosis factor alpha agents. Semin Arthritis Rheum. 2008 Jun;37(6):381-7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17977585
- ↑ Askling J, van Vollenhoven RF, Granath F et al Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment? Arthritis Rheum. 2009 Nov;60(11):3180-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19877027
- ↑ Listing J, Strangfeld A, Kekow J et al Does tumor necrosis factor alpha inhibition promote or prevent heart failure in patients with rheumatoid arthritis? Arthritis Rheum. 2008 Mar;58(3):667-77 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18311816
- ↑ 14.0 14.1 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: https://www.ncbi.nlm.nih.gov/pubmed/23926075
- ↑ 15.0 15.1 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: https://www.ncbi.nlm.nih.gov/pubmed/24938563
- ↑ Dixon WG, Watson KD, Lunt M et al Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res (Hoboken). 2010 Jun;62(6):755-63. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20535785
- ↑ 17.0 17.1 17.2 17.3 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26641955 <Internet> http://annals.org/article.aspx?articleid=2474360
- ↑ 18.0 18.1 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 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/15295313 Free full text
- ↑ 20.0 20.1 Peter I,Dubinsky M, Bressman S et al Anti-Tumor Necrosis Factor Therapy and Incidence of Parkinson Disease Among Patients With Inflammatory Bowel Disease. JAMA Neurol. Published online April 23, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29710331 https://jamanetwork.com/journals/jamaneurology/article-abstract/2679038
Olsen AL, Riise T, Scherzer CR. Discovering New Benefits From Old Drugs With Big Data-Promise for Parkinson Disease. JAMA Neurol. Published online April 23, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29710184 https://jamanetwork.com/journals/jamaneurology/article-abstract/2679036 - ↑ 21.0 21.1 Raaschou P, Soderling J, Turesson C, Askling J; ARTIS Study Group. Tumor necrosis factor inhibitors and cancer recurrence in Swedish patients with rheumatoid arthritis: A nationwide population-based cohort study. Ann Intern Med 2018 Sep 4; 169:291 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/30105374 <Internet> http://annals.org/aim/article-abstract/2697083/tumor-necrosis-factor-inhibitors-cancer-recurrence-swedish-patients-rheumatoid-arthritis
- ↑ 22.0 22.1 22.2 Godfrey MS, Friedman LN Tuberculosis and Biologic Therapies: Anti-Tumor Necrosis Factor-alpha and Beyond. Clin Chest Med. 2019 Dec;40(4):721-739 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31731980
- ↑ 23.0 23.1 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: https://www.ncbi.nlm.nih.gov/pubmed/39432288