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Tumor Necrosis Factor Inhibitors in the Management of Juvenile Idiopathic Arthritis

An Evidence-Based Review

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Abstract

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disorder of unknown origin that is often treated with a variety of disease-modifying agents. Tumor necrosis factor (TNF) inhibitors are a group of genetically engineered biologic agents that target the proinflammatory cytokine TNF. This review focuses on the use of TNF inhibitors in JIA.

Etanercept was the first TNF inhibitor approved for use in children with moderate to severe polyarticular-course JIA following encouraging results from a randomized, double-blind, placebo-controlled, multicenter trial in children. Open-label extension studies of the original trial involving 8 years of follow-up demonstrated the long-term safety and efficacy of etanercept in children. Other studies from established registries also corroborate the safety of etanercept in JIA. The second TNF inhibitor to be approved for use in JIA is adalimumab following recent favorable results from another randomized, placebo-controlled, multicenter study in polyarticular-course JIA. While infliximab is not approved by the US FDA for use in JIA, it is frequently used in clinical practice for this indication. However, because the chimeric structure of infliximab incorporates murine components, it has the potential for allergic and infusion reactions. Patient responses to individual TNF inhibitors may vary depending on concomitant medications such as methotrexate, and also on the category of JIA.

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References

  1. Carswell EA, Old LJ, Kassel RL, et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 1975 Sep; 72(9): 3666–70

    Article  PubMed  CAS  Google Scholar 

  2. Abbas AK, Lichtman AH. Cytokines. In: Cellular and molecular immunology. 5th ed. Philadelphia (PA): Elsevier Saunders, 2005: 243–74

    Google Scholar 

  3. Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008 Feb; 117(2): 244–79

    Article  PubMed  CAS  Google Scholar 

  4. Grell M, Wajant H, Zimmermann G, et al. The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor. Proc Natl Acad Sci USA 1998 Jan 20; 95(2): 570–5

    Article  PubMed  CAS  Google Scholar 

  5. Grell M, Douni E, Wajant H, et al. The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell 1995 Dec 1; 83(5): 793–802

    Article  PubMed  CAS  Google Scholar 

  6. Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med 1996 Jun 27; 334(26): 1717–25

    Article  PubMed  CAS  Google Scholar 

  7. Hehlgans T, Pfeffer K. The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 2005 May; 115(1): 1–20

    Article  PubMed  CAS  Google Scholar 

  8. Kollias G. TNF pathophysiology in murine models of chronic inflammation and autoimmunity. Semin Arthritis Rheum 2005 Apr; 34(5 Suppl. 1): 3–6

    Article  PubMed  CAS  Google Scholar 

  9. Kollias G, Kontoyiannis D, Douni E, et al. The role of TNF/TNFR in organ-specific and systemic autoimmunity: implications for the design of optimized ‘anti-TNF’ therapies. Curr Dir Autoimmun 2002; 5: 30–50

    Article  PubMed  CAS  Google Scholar 

  10. Grom AA, Murray KJ, Luyrink L, et al. Patterns of expression of tumor necrosis factor alpha, tumor necrosis factor beta, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondy-larthropathy. Arthritis Rheum 1996 Oct; 39(10): 1703–10

    Article  PubMed  CAS  Google Scholar 

  11. Eberhard BA, Laxer RM, Andersson U, et al. Local synthesis of both macrophage and T cell cytokines by synovial fluid cells from children with juvenile rheumatoid arthritis. Clin Exp Immunol 1994 May; 96(2): 260–6

    Article  PubMed  CAS  Google Scholar 

  12. Yetgin S, Ozen S, Saatci U, et al. Evaluation of tumour necrosis factor alpha, interferon gamma and granulocyte-macrophage colony stimulating factor levels in juvenile chronic arthritis. Rheumatology (Oxford) 1999 May; 38(5): 468–71

    Article  CAS  Google Scholar 

  13. Saxne T, Palladino Jr MA, Heinegard D, et al. Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum 1988 Aug; 31(8): 1041–5

    Article  PubMed  CAS  Google Scholar 

  14. Tak PP, Smeets TJ, Daha MR, et al. Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity. Arthritis Rheum 1997 Feb; 40(2): 217–25

    Article  PubMed  CAS  Google Scholar 

  15. Ulfgren AK, Lindblad S, Klareskog L, et al. Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis. Ann Rheum Dis 1995 Aug; 54(8): 654–61

    Article  PubMed  CAS  Google Scholar 

  16. Roux-Lombard P, Punzi L, Hasler F, et al. Soluble tumor necrosis factor receptors in human inflammatory synovial fluids. Arthritis Rheum 1993 Apr; 36(4): 485–9

    Article  PubMed  CAS  Google Scholar 

  17. Mangge H, Kenzian H, Gallistl S, et al. Serum cytokines in juvenile rheumatoid arthritis: correlation with conventional inflammation parameters and clinical subtypes. Arthritis Rheum 1995 Feb; 38(2): 211–20

    Article  PubMed  CAS  Google Scholar 

  18. Mangge H, Gallistl S, Schauenstein K. Long-term follow-up of cytokines and soluble cytokine receptors in peripheral blood of patients with juvenile rheumatoid arthritis. J Interferon Cytokine Res 1999 Sep; 19(9): 1005–10

    Article  PubMed  CAS  Google Scholar 

  19. Gattorno M, Picco P, Buoncompagni A, et al. Serum p55 and p75 tumour necrosis factor receptors as markers of disease activity in juvenile chronic arthritis. Ann Rheum Dis 1996 Apr; 55(4): 243–7

    Article  PubMed  CAS  Google Scholar 

  20. Butler DM, Malfait AM, Mason LJ, et al. DBA/1 mice expressing the human TNF-alpha transgene develop a severe, erosive arthritis: characterization of the cytokine cascade and cellular composition. J Immunol 1997 Sep 15; 159(6): 2867–76

    PubMed  CAS  Google Scholar 

  21. Klareskog L, McDevitt H. Rheumatoid arthritis and its animal models: the role of TNF-alpha and the possible absence of specific immune reactions. Curr Opin Immunol 1999 Dec; 11(6): 657–62

    Article  PubMed  CAS  Google Scholar 

  22. Williams RO, Feldmann M, Maini RN. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci USA 1992 Oct 15; 89(20): 9784–8

    Article  PubMed  CAS  Google Scholar 

  23. Enbrel [package insert]. Thousand Oaks (CA): Immunex Corporation, 1998–2009

  24. Humira [package insert]. North Chicago (IL): Abbott Laboratories, 2009

  25. Remicade [package insert]. Malvern (PA): Centocor Ortho Biotech, Inc., 2009

  26. Simponi [package insert]. Horsham (PA): Centocor Ortho Biotech Inc., 2009

  27. Cimzia [package insert]. Smyrna (GA): UCB, Inc., 2009

  28. Lovell DJ, Giannini EH, Reiff A, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med 2000 Mar 16; 342(11): 763–9

    Article  PubMed  CAS  Google Scholar 

  29. Giannini EH, Ruperto N, Ravelli A, et al. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997 Jul; 40(7): 1202–9

    PubMed  CAS  Google Scholar 

  30. Tzaribachev N, Kuemmerle-Deschner J, Eichner M, et al. Safety and efficacy of etanercept in children with juvenile idiopathic arthritis below the age of 4 years. Rheumatol Int 2008 Aug; 28(10): 1031–4

    Article  PubMed  CAS  Google Scholar 

  31. ten Cate R, van Suijlekom-Smit LW, Brinkman DM, et al. Etanercept in four children with therapy-resistant systemic juvenile idiopathic arthritis. Rheumatology (Oxford) 2002 Feb; 41(2): 228–9

    Article  Google Scholar 

  32. Horneff G, Schmeling H, Biedermann T, et al. The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 2004 Dec; 63(12): 1638–44

    Article  PubMed  CAS  Google Scholar 

  33. Kietz DA, Pepmueller PH, Moore TL. Clinical response to etanercept in polyarticular course juvenile rheumatoid arthritis. J Rheumatol 2001 Feb; 28(2): 360–2

    PubMed  CAS  Google Scholar 

  34. Kietz DA, Pepmueller PH, Moore TL. Therapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a two year period. Ann Rheum Dis 2002 Feb; 61(2): 171–3

    Article  PubMed  CAS  Google Scholar 

  35. Quartier P, Taupin P, Bourdeaut F, et al. Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 2003 Apr; 48(4): 1093–101

    Article  PubMed  CAS  Google Scholar 

  36. Russo RA, Katsicas MM, Zelazko M. Etanercept in systemic juvenile idiopathic arthritis. Clin Exp Rheumatol 2002 Sep–Oct; 20(5): 723–6

    PubMed  CAS  Google Scholar 

  37. Schmeling H, Mathony K, John V, et al. A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study. Ann Rheum Dis 2001 Apr; 60(4): 410–2

    Article  PubMed  CAS  Google Scholar 

  38. Kimura Y, Pinho P, Walco G, et al. Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 2005 May; 32(5): 935–42

    PubMed  CAS  Google Scholar 

  39. Prince FH, Twilt M, ten Cate R, et al. Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register. Ann Rheum Dis 2009 May; 68(5): 635–41

    Article  PubMed  CAS  Google Scholar 

  40. De Benedetti F, Martini A. Is systemic juvenile rheumatoid arthritis an interleukin 6 mediated disease? J Rheumatol 1998 Feb; 25(2): 203–7

    PubMed  Google Scholar 

  41. de Benedetti F, Massa M, Robbioni P, et al. Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. Arthritis Rheum 1991 Sep; 34(9): 1158–63

    Article  PubMed  Google Scholar 

  42. Pignatti P, Vivarelli M, Meazza C, et al. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J Rheumatol 2001 Jul; 28(7): 1670–6

    PubMed  CAS  Google Scholar 

  43. Tse SM, Burgos-Vargas R, Laxer RM. Anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondylarthropathy. Arthritis Rheum 2005 Jul; 52(7): 2103–8

    Article  PubMed  CAS  Google Scholar 

  44. Tse SM, Laxer RM, Babyn PS, et al. Radiologic Improvement of juvenile idiopathic arthritis-enthesitis-related arthritis following anti-tumor necrosis factor-alpha blockade with etanercept. J Rheumatol 2006 Jun; 33(6): 1186–8

    PubMed  Google Scholar 

  45. Henrickson M, Reiff A. Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. J Rheumatol 2004 Oct; 31(10): 2055–61

    PubMed  CAS  Google Scholar 

  46. Homeff G, Burgos-Vargas R. TNF-alpha antagonists for the treatment of juvenile-onset spondyloarthritides. Clin Exp Rheumatol 2002 Nov–Dec; 20(6 Suppl. 28): S137–42

    PubMed  CAS  Google Scholar 

  47. Prince FH, Twilt M, Jansen-Wijngaarden NC, et al. Effectiveness of a once weekly double dose of etanercept in patients with juvenile idiopathic arthritis: a clinical study. Ann Rheum Dis 2007 May; 66(5): 704–5

    Article  PubMed  Google Scholar 

  48. Prince FH, van Suijlekom-Smit LW. Initiating etanercept in a once weekly dose in children with juvenile idiopathic arthritis. Rheumatol Int 2008 Feb; 28(4): 8; author reply, 399

    Article  Google Scholar 

  49. Horneff G, Ebert A, Fitter S, et al. Safety and efficacy of once weekly etanercept 0.8 mg/kg in a multicentre 12 week trial in active polyarticular course juvenile idiopathic arthritis. Rheumatology (Oxford) 2009 Aug; 48(8): 916–9

    Article  CAS  Google Scholar 

  50. Kuemmerle-Deschner JB, Horneff G. Safety and efficacy of once-weekly application of etanercept in children with juvenile idiopathic arthritis. Rheumatol Int 2007 Dec; 28(2): 153–6

    Article  PubMed  CAS  Google Scholar 

  51. Yim DS, Zhou H, Buckwalter M, et al. Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients withjuvenile rheumatoid arthritis. J Clin Pharmacol 2005 Mar; 45(3): 246–56

    Article  PubMed  CAS  Google Scholar 

  52. Lovell DJ, Giannini EH, Reiff A, et al. Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, open-label, extended-treatment trial. Arthritis Rheum 2003 Jan; 48(1): 218–26

    Article  PubMed  CAS  Google Scholar 

  53. Lovell DJ, Reiff A, Jones OY, et al. Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 2006 Jun; 54(6): 1987–94

    Article  PubMed  Google Scholar 

  54. Lovell DJ, Reiff A, Ilowite NT, et al. Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum 2008 May; 58(5): 1496–504

    Article  PubMed  CAS  Google Scholar 

  55. Giannini EH, Ilowite NT, Lovell DJ, et al. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum 2009 Sep; 60(9): 2794–804

    Article  PubMed  CAS  Google Scholar 

  56. Horneff G, De Bock F, Foeldvari I, et al. Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis 2009 Apr; 68(4): 519–25

    Article  PubMed  CAS  Google Scholar 

  57. Halbig M, Horneff G. Improvement of functional ability in children with juvenile idiopathic arthritis by treatment with etanercept. Rheumatol Int. Epub 2009 May 16

  58. Prince FH, Geerdink LM, Borsboom GJ, et al. Major improvements in health-related quality of life during the use of etanercept in patients with previously refractory juvenile idiopathic arthritis. Ann Rheum Dis 2010 Jan; 69(1): 138–42

    Article  PubMed  CAS  Google Scholar 

  59. Nielsen S, Ruperto N, Gerloni V, et al. Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis. Clin Exp Rheumatol 2008 Jul–Aug; 26(4): 688–92

    PubMed  CAS  Google Scholar 

  60. Simonini G, Giani T, Stagi S, et al. Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis. Rheumatology (Oxford) 2005 Jun; 44(6): 777–80

    Article  CAS  Google Scholar 

  61. Wallace CA, Ruperto N, Giannini E, Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology International Trials Organization, Pediatric Rheumatology Collaborative Study Group. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004 Nov; 31(11): 2290–4

    PubMed  Google Scholar 

  62. Prince FH, Twilt M, Simon SC, et al. When and how to stop etanercept after successful treatment of patients with juvenile idiopathic arthritis. Ann Rheum Dis 2009 Jul; 68(7): 1228–9

    Article  PubMed  CAS  Google Scholar 

  63. Gerloni V, Pontikaki I, Gattinara M, et al. Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. Arthritis Rheum 2005 Feb; 52(2): 548–53

    Article  PubMed  CAS  Google Scholar 

  64. Norambuena RX, Mallol J, Rios MG, et al. Therapeutic effects of the anti-tumor necrosis factor monoclonal antibody, infliximab, in four children with refractory juvenile idiopathic arthritis. Allergol Immunopathol (Madr) 2007 Mar–Apr; 35(2): 52–6

    Article  CAS  Google Scholar 

  65. Levalampi T, Honkanen V, Lahdenne P, et al. Effects of infliximab on cyto-kines, myeloperoxidase, and soluble adhesion molecules in patients with juvenile idiopathic arthritis. Scand J Rheumatol 2007 May–Jun; 36(3): 189–93

    Article  PubMed  CAS  Google Scholar 

  66. Ruperto N, Lovell DJ, Cuttica R, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 2007 Sep; 56(9): 3096–106

    Article  PubMed  CAS  Google Scholar 

  67. Ruperto N, Lovell DJ, Cuttica R, et al. Long-term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular course juvenile rheumatoid arthritis: findings from an open-label treatment extension. Ann Rheum Dis 2010 Apr; 69(4): 718–22

    Article  PubMed  CAS  Google Scholar 

  68. Gerloni V, Pontikaki I, Gattinara M, et al. Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients. Ann Rheum Dis 2008 Aug; 67(8): 1145–52

    Article  PubMed  CAS  Google Scholar 

  69. Elliott MJ, Woo P, Charles P, et al. Suppression of fever and the acute-phase response in a patient with juvenile chronic arthritis treated with monoclonal antibody to tumour necrosis factor-alpha (cA2). Br J Rheumatol 1997 May; 36(5): 589–93

    Article  PubMed  CAS  Google Scholar 

  70. Billiau AD, Cornillie F, Wouters C. Infliximab for systemic onset juvenile idiopathic arthritis: experience in 3 children. J Rheumatol 2002 May; 29(5): 1111–4

    PubMed  Google Scholar 

  71. Katsicas MM, Russo RA. Use of infliximab in patients with systemic juvenile idiopathic arthritis refractory to etanercept. Clin Exp Rheumatol 2005 Jul–Aug; 23(4): 545–8

    PubMed  CAS  Google Scholar 

  72. Burgos-Vargas R. A case of childhood-onset ankylosing spondylitis: diagnosis and treatment. Nat Clin Pract Rheumatol 2009 Jan; 5(1): 52–7

    Article  PubMed  Google Scholar 

  73. D’Agostino MA, Breban M, Said-Nahal R, et al. Refractory inflammatory heel pain in spondylarthropathy: a significant response to infliximab documented by ultrasound. Arthritis Rheum 2002 Mar; 46(3): 840–1; author reply, 841–3

    Article  PubMed  Google Scholar 

  74. Schmeling H, Horneff G. Infliximab in two patients withjuvenile ankylosing spondylitis. Rheumatol Int 2004 May; 24(3): 173–6

    Article  PubMed  Google Scholar 

  75. Nerome Y, Imanaka H, Nonaka Y, et al. Switching the therapy from etanercept to infliximab in a child with rheumatoid factor positive polyarticular juvenile idiopathic arthritis. Mod Rheumatol 2007; 17(6): 526–8

    Article  PubMed  Google Scholar 

  76. Favalli EG, Arreghini M, Arnoldi C, et al. Anti-tumor necrosis factor alpha switching in rheumatoid arthritis and juvenile chronic arthritis. Arthritis Rheum 2004 Apr 15; 51(2): 301–2

    Article  PubMed  Google Scholar 

  77. Lahdenne P, Vahasalo P, Honkanen V. Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis 2003 Mar; 62(3): 245–7

    Article  PubMed  CAS  Google Scholar 

  78. Lovell DJ, Ruperto N, Goodman S, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med 2008 Aug 21; 359(8): 810–20

    Article  PubMed  CAS  Google Scholar 

  79. de Vries MK, van der Horst-Bruinsma IE, Wolbink GJ. Adalimumab in juvenile rheumatoid arthritis. N Engl J Med 2008 Dec 4; 359(23): 2496; author reply, 2496–7

    PubMed  Google Scholar 

  80. Abbott. Study of the human anti-tumor necrosis factor (TNF) monoclonal antibody adalimumab in children with polyarticular juvenile idiopathic arthritis (JIA) [ClinicalTrials.gov identifier NCT00048542]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Aug 2]

  81. Katsicas MM, Russo RA. Use of adalimumab in patients withjuvenile idiopathic arthritis refractory to etanercept and/or infliximab. Clin Rheumatol 2009 Aug; 28(8): 985–8

    Article  PubMed  Google Scholar 

  82. Olivieri I, Scarano E, Gigliotti P, et al. Successful treatment of juvenile-onset HLA-B27-associated severe and refractory heel thesitis with adalimumab documented by magnetic resonance imaging. Rheumatology (Oxford) 2006 Oct; 45(10): 1315–7

    Article  CAS  Google Scholar 

  83. Abbott. Active juvenile idiopathic arthritis (JIA) compassionate use [ClinicalTrials.gov identifier NCT00775437]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Aug 2]

  84. Abbott. Juvenile idiopathic arthritis (JIA) registry (STRIVE) [ClinicalTrials.gov identifier NCT00783510]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Aug 2]

  85. Abbott. Safety, efficacy, and pharmacokinetics of adalimumab in Japanese children with juvenile rheumatoid arthritis [ClinicalTrials.gov identifier NCT00690573]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Aug 2]

  86. Keystone E, Heijde D, Mason Jr D, et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 2008 Nov; 58(11): 3319–29

    Article  PubMed  CAS  Google Scholar 

  87. Choy EH, Hazleman B, Smith M, et al. Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatology (Oxford) 2002 Oct; 41(10): 1133–7

    Article  CAS  Google Scholar 

  88. Fleischmann R, Vencovsky J, van Vollenhoven RF, et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis 2009 Jun; 68(6): 805–11

    Article  PubMed  CAS  Google Scholar 

  89. Smolen J, Landewe RB, Mease P, et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study: a randomised controlled trial. Ann Rheum Dis 2009 Jun; 68(6): 797–804

    Article  PubMed  CAS  Google Scholar 

  90. Barnes T, Moots R. Targeting nanomedicines in the treatment of rheumatoid arthritis: focus on certolizumab pegol. Int J Nanomedicine 2007; 2(1): 3–7

    Article  PubMed  CAS  Google Scholar 

  91. Emery P, Fleischmann RM, Moreland LW, et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum 2009 Aug; 60(8): 2272–83

    Article  PubMed  CAS  Google Scholar 

  92. Keystone EC, Genovese MC, Klareskog L, et al. Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis 2009 Jun; 68(6): 789–96

    Article  PubMed  CAS  Google Scholar 

  93. Smolen JS, Kay J, Doyle MK, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 2009 Jul 18; 374(9685): 210–21

    Article  PubMed  CAS  Google Scholar 

  94. Kay J, Matteson EL, Dasgupta B, et al. Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum 2008 Apr; 58(4): 964–75

    Article  PubMed  CAS  Google Scholar 

  95. Zhou H, Jang H, Fleischmann RM, et al. Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol 2007 Mar; 47(3): 383–96

    Article  PubMed  CAS  Google Scholar 

  96. Simard JF, Neovius M, Hagelberg S, et al. Juvenile idiopathic arthritis and risk of cancer: a nationwide cohort study. EULAR 2010 [abstract]. Ann Rheum Dis 2010; 69Suppl. 3: 81

    Google Scholar 

  97. Harrison M, Nordstrom B, Gu Y, et al. Risk of malignancy in biologics-naive juvenile arthritis patients. EULAR 2010 [abstract]. Ann Rheum Dis 2010; 69Suppl. 3: 631

    Google Scholar 

  98. Questions and answers — TNF blockers 8/25/2009 [online]. Available from URL: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm180694.htm [Accessed 2009 Sep 3]

  99. Diak P, Siegel J, Grenade LL, et al. Tumor necrosis factor α blockers and malignancy in children. Arthritis Rheum 2010 Aug; 62(8): 2517–24

    Article  PubMed  Google Scholar 

  100. McCroskery P, Wallace CA, Lovell DJ, et al. Summary of worldwide pediatric malignancies reported after exposure to etanercept. Pediatr Rheumatol Online J 2010 Jun 14; 8: 18

    Article  Google Scholar 

  101. Yokota S, Imagawa T, Mori M, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 2008 Mar 22; 371(9617): 998–1006

    Article  PubMed  CAS  Google Scholar 

  102. Yokota S, Miyamae T, Imagawa T, et al. Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis. Clin Rev Allergy Immunol 2005 Jun; 28(3): 231–8

    Article  PubMed  CAS  Google Scholar 

  103. Verbsky JW, White AJ. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol 2004 Oct; 31(10): 2071–5

    PubMed  Google Scholar 

  104. Lequerre T, Quartier P, Rosellini D, et al. Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis 2008 Mar; 67(3): 302–8

    Article  PubMed  CAS  Google Scholar 

  105. Sulpice M, Deslandre CJ, Quartier P. Efficacy and safety of TNFalpha antagonist therapy in patients with juvenile spondyloarthropathies. Joint Bone Spine 2009 Jan; 76(1): 24–7

    Article  PubMed  CAS  Google Scholar 

  106. Foeldvari I, Nielsen S, Kummerle-Deschner J, et al. Tumor necrosis factor-alpha blocker in treatment of juvenile idiopathic arthritis-associated uveitis refractory to second-line agents: results of a multinational survey. J Rheumatol 2007 May; 34(5): 1146–50

    PubMed  CAS  Google Scholar 

  107. Richards JC, Tay-Kearney ML, Murray K, et al. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Experiment Ophthalmol 2005 Oct; 33(5): 461–8

    Article  PubMed  Google Scholar 

  108. Reiff A, Takei S, Sadeghi S, et al. Etanercept therapy in children with treatment-resistant uveitis. Arthritis Rheum 2001 Jun; 44(6): 1411–5

    Article  PubMed  CAS  Google Scholar 

  109. Reiff A. Long-term outcome of etanercept therapy in children with treatment-refractory uveitis. Arthritis Rheum 2003 Jul; 48(7): 2079–80

    Article  PubMed  Google Scholar 

  110. Tynjala P, Lindahl P, Honkanen V, et al. Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis 2007 Apr; 66(4): 548–50

    Article  PubMed  CAS  Google Scholar 

  111. Tynjala P, Kotaniemi K, Lindahl P, et al. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford) 2008 Mar; 47(3): 339–44

    Article  CAS  Google Scholar 

  112. Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr 2006 Oct; 149(4): 572–5

    Article  PubMed  CAS  Google Scholar 

  113. Biester S, Deuter C, Michels H, et al. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol 2007 Mar; 91(3): 319–24

    Article  PubMed  Google Scholar 

  114. Mangge H, Heinzl B, Grubbauer HM, et al. Therapeutic experience with infliximab in a patient with polyarticular juvenile idiopathic arthritis and uveitis. Rheumatol Int 2003 Sep; 23(5): 258–61

    Article  PubMed  Google Scholar 

  115. Smith JA, Thompson DJ, Whitcup SM, et al. A randomized, placebo-controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Rheum 2005 Feb 15; 53(1): 18–23

    Article  PubMed  CAS  Google Scholar 

  116. Saurenmann RK, Levin AV, Feldman BM, et al. Risk of new-onset uveitis in patients with juvenile idiopathic arthritis treated with anti-TNFalpha agents. J Pediatr 2006 Dec; 149(6): 833–6

    Article  PubMed  CAS  Google Scholar 

  117. Saurenmann RK, Levin AV, Rose JB, et al. Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology (Oxford) 2006 Aug; 45(8): 982–9

    Article  CAS  Google Scholar 

  118. Schmeling H, Horneff G. Etanercept and uveitis in patients with juvenile idiopathic arthritis. Rheumatology (Oxford) 2005 Aug; 44(8): 1008–11

    Article  CAS  Google Scholar 

  119. Rajaraman RT, Kimura Y, Li S, et al. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology 2006 Feb; 113(2): 308–14

    Article  PubMed  Google Scholar 

  120. Theodossiadis PG, Markomichelakis NN, Sfikakis PP. Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina 2007 Apr–May; 27(4): 399–413

    Article  PubMed  Google Scholar 

  121. Brik R, Gepstein V, Shahar E, et al. Tumor necrosis factor blockade in the management of children with orphan diseases. Clin Rheumatol 2007 Oct; 26(10): 1783–5

    Article  PubMed  Google Scholar 

  122. Haapasaari J, Kautiainen H, Hannula S, et al. Good results from combining etanercept to prevailing DMARD therapy in refractory juvenile idiopathic arthritis. Clin Exp Rheumatol 2002 Nov–Dec; 20(6): 867–70

    PubMed  CAS  Google Scholar 

  123. Bellofiore B, Matarese A, Balato N, et al. Prevention of tuberculosis in patients taking tumor necrosis factor-alpha blockers. J Rheumatol Suppl 2009 Aug; 83: 76–7

    Article  PubMed  CAS  Google Scholar 

  124. Minden K, Kiessling U, Listing J, et al. Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy. J Rheumatol 2000 Sep; 27(9): 2256–63

    PubMed  CAS  Google Scholar 

  125. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Trial of early aggressive drug therapy in juvenile idiopathic arthritis [Clinical-Trials.gov identifier NCT00443430]. US National Institutes of Health, Clinical-Trials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Aug 2]

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Acknowledgements

We would like to thank our pharmacist, Barbara Marquardt, for her help with table I. No sources of funding were used to prepare this manuscript. Carol Wallace has received grants from Amgen, Centocor and Pfizer. Susan Shenoi has no conflicts of interest to declare that are directly relevant to the content of this review.

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  1. Seattle Children’s Hospital, Division of Pediatric Rheumatology, University of Washington, 4800 Sand Point Way NE, Seattle, Washington, 98105, USA

    Susan Shenoi &  Carol A. Wallace

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  1. Susan Shenoi
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Correspondence to Carol A. Wallace.

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Shenoi, S., Wallace, C.A. Tumor Necrosis Factor Inhibitors in the Management of Juvenile Idiopathic Arthritis. Pediatr-Drugs 12, 367–377 (2010). https://doi.org/10.2165/11532610-000000000-00000

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