• Giuseppe Tridente


Etanercept (Enbrel®, Immunex, Amgen, and Pfizer) is a fusion protein combining the Fc domain of human IgG1 to the extracellular portion of the tumor necrosis factor receptor-2 (TNFR2, p75). TNFR2 binds to soluble TNFs (TNFα, TNFβ -LTα-), thus blocking the interaction with their natural receptors and interrupting the activation of TNF-related proinflammatory pathways.


Rheumatoid Arthritis Tumor Necrosis Factor Rheumatoid Arthritis Patient Juvenile Idiopathic Arthritis Familial Mediterranean Fever 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

307171_1_En_45_MOESM1_ESM.xls (64 kb)
Supplementary material 1 (XLS 65 kb)


  1. 1.
    Etanercept (Enbrel®) BLA 98-0286 Clinical Review for RA, FDA, Dec 1998Google Scholar
  2. 2.
    Etanercept (Enbrel®) BLA 98-0286 Clinical Review for JRA, FDA, Nov 1998Google Scholar
  3. 3.
    Etanercept (Enbrel®) BLA 103795/5123 Medical Review for AS, FDA, July 2003Google Scholar
  4. 4.
    Etanercept (Enbrel®) BLA 103795/5102 Medical Review for PsA, FDA, Aug 2003Google Scholar
  5. 5.
    Etanercept (Enbrel®) WC500027358 Scientific Discussion for RA, EMEA Oct 2004Google Scholar
  6. 6.
    Etanercept (Enbrel®) WC500027362 Assessment Report for pediatric Ps, EMEA, Nov 2008Google Scholar
  7. 7.
    Etanercept (Enbrel®) WC500113064 Assessment Report for pediatric Ps, EMEA, Sept 2011Google Scholar
  8. 8.
    Etanercept (Enbrel®) WC50011281 Assessment Report for JIA. EMEA, June 2012Google Scholar
  9. 9.
    Etanercept (Enbrel®) Prescribing Information, Pfizer 2012Google Scholar
  10. 10.
    Etanercept (Enbrel®) WC500027361 EPAR Annex I, EMEA 2013Google Scholar
  11. 11.
    Etanercept (Enbrel®) WC500137356, WC500137357, WC500137358, WC500137359, Assessment Reports (Ps, JRA, and RA), EMEA, Jan 2013Google Scholar
  12. 12.
    Tracey D, Klareskog L, Sasso EH et al (2008) Tumor necrosis factor antagonist mechanism of action: a comprehensive review. Pharmacol Ther 117:244–279PubMedCrossRefGoogle Scholar
  13. 13.
    Horiuki T, Mitoma H, Harashima S et al (2010) Transmembrane TNFα: structure, function and interaction with anti-TNF agents. Rheumatology 49:1215–1228CrossRefGoogle Scholar
  14. 14.
    Edwards CK, Green JS, Volk HD et al (2012) Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone. Front Immunol. doi: 10.3389/fimmu.2012.00366 Google Scholar
  15. 15.
    Konsta M, Bamias G, Tektonidou MG et al (2012) Increased levels of soluble TNF-like cytokine 1A in ankylosing spondylitis. Rheumatology. doi: 10.1093/rheumatology/kes316 PubMedGoogle Scholar
  16. 16.
    Garcês S, Demengeot J, Benito-Garcia E (2012) The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis. Ann Rheum Dis 0:1–9. doi: 10.1136/annrheumdis-2012-202220 Google Scholar
  17. 17.
    Lim LL, Fraunfelder FW, Rosenbaum JT (2007) Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 56:3248–3252PubMedCrossRefGoogle Scholar
  18. 18.
    Minden K, Niewerth M, Zink A et al (2012) Long-term outcome of patients with JIA treated with etanercept, results of the biologic register JuMBO. Rheumatology 51:1407–1415PubMedCrossRefGoogle Scholar
  19. 19.
    Jobanputra P, Maggs F, Deeming A et al (2012) A randomized efficacy and discontinuation study of etanercept versus adalimumab (RED SEA) for rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study of first TNF inhibitor use: outcomes over 2 years. BMJ Open 2:e001395PubMedCrossRefGoogle Scholar
  20. 20.
    Song IH, Hermann KG, Haibel H et al (2011) Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48 week randomized controlled trial. Ann Rheum Dis 70:590–596PubMedCrossRefGoogle Scholar
  21. 21.
    Smolen JS, Nash P, Durez P et al (2013) Maintenance, reduction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis (PRESERVE): a randomized controlled trial. Lancet Online. doi: 10.1016/S0140-6736(12)61811 Google Scholar
  22. 22.
    Cantini F, Niccoli L, Cassarà E et al (2013) Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study. Biol Targets Ther 7:1–6CrossRefGoogle Scholar
  23. 23.
    Brezinski EA, Armstrong AW (2012) Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy. PLoS ONE 7:e33486PubMedCrossRefGoogle Scholar
  24. 24.
    Esposito M, Giunta A, Mazzotta A et al (2012) Efficacy and safety of subcutaneous anti-tumor necrosis factor-alpha agents, etanercept and adalimumab, in elderly patients affected by psoriasis and psoriatic arthritis: an observational long-term study. Dermatology. doi: 10.1159/000345623 PubMedGoogle Scholar
  25. 25.
    Kim HY, Hsu PN, Barba M et al (2012) Randomized comparison of etanercept with usual therapy in an Asian population with active rheumatoid arthritis: the APPEAL trial. Int J Rheum Dis 15:188–196PubMedCrossRefGoogle Scholar
  26. 26.
    Barrientos N, García-Sánchez S, Domínguez JD (2012) Lichenoid eruption induced by etanercept. Dermatol Online J 18:15PubMedGoogle Scholar
  27. 27.
    Lamrock E, Brown P (2012) Development of cutaneous sarcoidosis during treatment with tumour necrosis alpha factor antagonists. Australas J Dermatol 53:e87–e90PubMedCrossRefGoogle Scholar
  28. 28.
    Fonollosa A, Artaraz J, Martinez-Berriotxoa A et al (2012) Sarcoid intermediate uveitis following etanercept treatment: a case report and review of the literature. Ocul Immunol Inflamm. doi: 10.3109/09273948.2011.623212 PubMedGoogle Scholar
  29. 29.
    Hawryluk EB, Linskey KR, Duncan LM et al (2012) Broad range of adverse cutaneous eruptions in patients on TNF-alpha antagonists. J Cut Path 39:481–492CrossRefGoogle Scholar
  30. 30.
    Scmidt E, Wetter DA, Ferguson SB et al (2012) Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo clinic experience, 1998 to 2010. J Am Acad Dermatol. doi: 10.1016/j.jaad.2011.05.038 Google Scholar
  31. 31.
    Martinez Santana V, Izquierdo Navarro M, Calleja Hernandez MA et al (2012) Severe pancytopenia following etanercept administration in rheumatoid arthritis. Intern J Rheum Dis 15:e78–e79CrossRefGoogle Scholar
  32. 32.
    Khaja M, Menon L, Niazi M et al (2012) Diffuse alveolar hemorrhage and acute respiratory distress syndrome during treatment of rheumatoid arthritis with etanercept. J Bronchol Interv Pulmonol 19:228–231CrossRefGoogle Scholar
  33. 33.
    Rolle AS, Zimmermann B, Poon SH (2013) Etanercept-induced Henoch-Schönlein purpura in a patient with ankylosing spondylitis. J Clin Rheumatol. doi: 10.1097/RHU.0b013e3182863027 PubMedGoogle Scholar
  34. 34.
    Sadlier M, Connaghan G, Kirby B (2012) Acute myeloid leukemia presenting with cutaneous infiltrates in a patient receiving etanercept for chronic lymphocytic vasculitis. J Am Acad Dermatol. doi: 10.1016/j.jaad.2012.03.037 Google Scholar
  35. 35.
    Mrabet D, Selmi A, Filali A et al (2012) Maladie de Crohn induite par l’étanercept: à propos d’une nouvelle observation. Rev Med Liege 67:619–622PubMedGoogle Scholar
  36. 36.
    Oikonomou KA, Kapsoritakis AN, Tsiopoulos FD et al (2010) Emergence of Crohn’s disease in juvenile arthritis during treatment with etanercept: a casual link or a mere coincidence? J Gastrointest Liver Dis 19:342Google Scholar
  37. 37.
    Lee YH, Bae SC, Song GG (2013) Hepatitis B virus (HBV) reactivation in rheumatic patients with hepatitis core antigen (HBV occult carriers) undergoing anti-tumor necrosis factor therapy. Clin Exp Rheumatol 31:116–121Google Scholar
  38. 38.
    Gaujoux C, Giampietro C, Gaujoux T et al (2012) Scleritis: a paradoxical effect of etanercept? Etanercept-associated inflammatory eye disease. J Rheumatol 39:233–239PubMedCrossRefGoogle Scholar
  39. 39.
    Herrinton LJ, Liu L, Chen L et al (2012) Association between anti-TNF-α therapy and all-cause mortality. Pharmacoepidemiol Drug Saf 21:1311–1320PubMedCrossRefGoogle Scholar
  40. 40.
    Simard JF, Noevius M, Askling J (2012) Mortality rates in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors. Drug-specific comparisons in the Swedish Biologics Registry. Arthritis Rheum 64:3502–3510Google Scholar
  41. 41.
    Karampetsou MP, Liossis SNC, Sfikakis PP (2010) TNF-α antagonists beyond approved indications: stories of success and prospects for the future. Q J Med 103:917–928CrossRefGoogle Scholar
  42. 42.
    Anink J, Otten MH, Prince FHM et al (2012) Tumour necrosis factor-blocking agents in persistent oligoarticular juvenile idiopathic arthritis: results from the Dutch Arthritis and biologicals in children register. Rheumatology. doi: 10.1093/rheumatology/kes373 PubMedGoogle Scholar
  43. 43.
    Arida A, Fragiadaki K, Giavri E et al (2011) Anti-TNF agents for Behçet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum 41:61–70PubMedCrossRefGoogle Scholar
  44. 44.
    Watanabe S, Alzawa-Yashiro T, Tsuruga K et al (2012) A young girl with refractory intestinal Behçet’s disease: a case report and review of literatures on pediatric cases who received an anti-tumor necrosis factor agent. Rheumatol Int. doi: 10.1007/s00296-012-2628-5
  45. 45.
    Guedes S, Moreira A, Menezes N et al (2012) Treatment of thalidomide resistant pyoderma gangrenosum with etanercept. Acta Dermatovenereol Croat 20:175–180Google Scholar
  46. 46.
    Van Rappard DC, Limpens J, Mekkes JR (2012) The off-label treatment of severe hidradenitis suppurativa with TNF-α inhibitors: a systematic review. J Dermatol Treat. doi: 10.3109/09546634.2012.674193 Google Scholar
  47. 47.
    Kim NH, Torchia D, Rouhani P et al (2011) Tumor necrosis-α in vitiligo: direct correlation between tissue levels and clinical parameters. Cutan Ocul Toxicol 30:225–227PubMedCrossRefGoogle Scholar
  48. 48.
    Nin M, Tokunaga D, Ishii N et al (2013) Case of coexisting psoriasic arthritis and bullous pemphigoid improved by etanercept. J Dermatol 40:55–56PubMedCrossRefGoogle Scholar
  49. 49.
    Silva F, Cisternas M, Specks U (2012) TNF-α blocker therapy and solid malignancy risk in ANCA-associated vasculitis. Curr Rheumatol Rep 14:501–508PubMedCrossRefGoogle Scholar
  50. 50.
    Amato AA and The Muscle Study Group (2011) A randomized, pilot trial of etanercept in dermatomyositis. Ann Neurol 70:427–436CrossRefGoogle Scholar
  51. 51.
    Tobinik E (2011) Rapid improvement of chronic stroke deficits after perispinal etanercept. Three consecutive cases. CNS Drugs 25:145–156CrossRefGoogle Scholar
  52. 52.
    Javed Q, Murtaza I (2013) Therapeutic potential of tumour necrosis factor-alpha antagonists in patients with chronic heart failure. Heart Lung Circ. doi: 10.1016/j.hlc.2012.12.002 PubMedGoogle Scholar
  53. 53.
    Aaron SD, Vandemheen KL, Maltais F et al (2013) TNF-α antagonists for acute exacerbations of COPD: a randomized double-blind controlled trial. Thorax 68:142–148PubMedCrossRefGoogle Scholar
  54. 54.
    Akgul O, Kilic E, Kilic G et al (2012) Efficacy and safety of biologic treatments in Familial Mediterranean Fever. Am J Med Sci. doi:  10.1097/MAJ.0b013e318277083b
  55. 55.
    Haraoui B, Krelenbaum M (2009) Emergence of Crohn’s disease during treatment with the anti-tumor necrosis factor agent etanercept for ankylosing spondylitis: possible mechanisms of action. Semin Arthritis Rheum 39:176–181PubMedCrossRefGoogle Scholar
  56. 56.
    Bes C, Yazici A, Soy M (2012) Monoclonal anti-TNF antibodies can elevate hemoglobin level in patients with ankylosing spondylitis. Rheumatol Int. doi: 10.1007/s00296-012-2539-5 Google Scholar
  57. 57.
    Jančić I, Arsenović-Ranin N, Sefic-Bulilica M et al (2012) 174G/C interleukin-6 gene promoter polymorphism predicts therapeutic response to etanercept in rheumatoid arthritis. Rheumatol Int. doi: 10.1007/s00296-012-2586-y PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  1. 1.University of VeronaVeronaItaly

Personalised recommendations