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Published in: Pediatric Drugs 3/2004

01-05-2004 | Leading Article

Biologic Agents for the Treatment of Juvenile Rheumatoid Arthritis

Current Status

Authors: Ruy Carrasco, Judith A. Smith, Professor Daniel Lovell

Published in: Pediatric Drugs | Issue 3/2004

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Abstract

Biologic therapies, primarily anticytokine therapies, are being increasingly used in patients with juvenile rheumatoid arthritis (JRA). Levels of a variety of proinflammatory cytokines have been shown to be elevated in the peripheral blood and synovial fluid and tissue in children with JRA.
In a blinded, randomized, controlled trial in children with severe, long-standing, polyarticular-course JRA not responsive to standard therapies, etanercept showed a statistically significantly greater response rate than placebo. Approximately 75% of these children responded to etanercept. Etanercept has been efficacious in 50–60% of children with active systemic JRA in open clinical trials with acceptable tolerance. Adverse events seen in children treated with etanercept have been similar in type and frequency to those reported in adults.
Infliximab has been studied in several open clinical trials in both polyarticular and systemic JRA and found to, overall, have demonstrated efficacy in approximately 60% of patients. Approximately 3–5% of patients have demonstrated infusion reactions or frank allergic reactions and 9% developed new autoantibodies.
Anakinra has been studied in children with polyarticular JRA. Approximately 65% of patients developed injection-site reactions and 68% demonstrated a response to the medication. Anakinra may have increased efficacy in systemic JRA.
Interleukin (IL)-6 is highly related to the systemic disease manifestations in systemic JRA and two patients treated with a monoclonal antibody to the IL-6 receptor have demonstrated significant improvement with prolonged clinical control with continued treatment.
A particular pediatric concern is the effect of immunosuppressive biologics in children who are exposed to or develop varicella. These children should be treated, both in terms of prophylaxis and aggressive antivaricella treatment, as for other immunosuppressed children.
Anticytokine biologics have demonstrated great promise in the treatment of JRA and a variety of other pediatric rheumatic diseases, although at this time the randomized, placebo-controlled data are limited only to etanercept in children with polyarticular JRA. Randomized trials are ongoing to better define both the efficacy and safety of these novel treatments for children with JRA and other rheumatic diseases.
Literature
1.
go back to reference 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): 218–26PubMedCrossRef 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): 218–26PubMedCrossRef
2.
go back to reference Ilowite NT. Current treatment of juvenile rheumatoid arthritis. Pediatrics 2002 Jan; 109(1): 109–15PubMedCrossRef Ilowite NT. Current treatment of juvenile rheumatoid arthritis. Pediatrics 2002 Jan; 109(1): 109–15PubMedCrossRef
3.
go back to reference 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 spondylarthropathy. Arthritis Rheum 1996 Oct; 39(10): 1703–10PubMedCrossRef 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 spondylarthropathy. Arthritis Rheum 1996 Oct; 39(10): 1703–10PubMedCrossRef
4.
go back to reference van den Berg WB. Uncoupling of inflammatory and destructive mechanisms in arthritis. Semin Arthritis Rheum 2001 Apr; 30(5 Suppl. 2): 7–16PubMedCrossRef van den Berg WB. Uncoupling of inflammatory and destructive mechanisms in arthritis. Semin Arthritis Rheum 2001 Apr; 30(5 Suppl. 2): 7–16PubMedCrossRef
5.
go back to reference Jorgensen C, Apparailly F, Sany J. Immunological evaluation of cytokine and anticytokine immunotherapy in vivo: what have we learnt? Ann Rheum Dis 1999 Mar; 58(3): 136–41PubMedCrossRef Jorgensen C, Apparailly F, Sany J. Immunological evaluation of cytokine and anticytokine immunotherapy in vivo: what have we learnt? Ann Rheum Dis 1999 Mar; 58(3): 136–41PubMedCrossRef
6.
go back to reference Abbas A, Lichtman AH, Pober JS. Cellular and molecular immunology. Philadelphia (PA): WB Saunders, 2000: 553 Abbas A, Lichtman AH, Pober JS. Cellular and molecular immunology. Philadelphia (PA): WB Saunders, 2000: 553
7.
go back to reference Beutler BA. The role of tumor necrosis factor in health and disease. J Rheumatol 1999 May; 26Suppl. 57: 16–21 Beutler BA. The role of tumor necrosis factor in health and disease. J Rheumatol 1999 May; 26Suppl. 57: 16–21
8.
go back to reference Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech 2000 Aug; 50(3): 184–95PubMedCrossRef Idriss HT, Naismith JH. TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech 2000 Aug; 50(3): 184–95PubMedCrossRef
9.
go back to reference Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 1986 Aug; 322(6079): 547–9PubMedCrossRef Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 1986 Aug; 322(6079): 547–9PubMedCrossRef
10.
11.
go back to reference Austen K, Frank M, Atkinson J, et al. Samter’s immunologic diseases. Vol. 2. Philadelphia (PA): Lippincott Williams & Wilkins, 2001: 1318 Austen K, Frank M, Atkinson J, et al. Samter’s immunologic diseases. Vol. 2. Philadelphia (PA): Lippincott Williams & Wilkins, 2001: 1318
12.
go back to reference Deleuran BW, Chu CQ, Field M, et al. Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis: implications for local actions of tumor necrosis factor alpha. Arthritis Rheum 1992 Oct; 35(10): 1170–8PubMedCrossRef Deleuran BW, Chu CQ, Field M, et al. Localization of tumor necrosis factor receptors in the synovial tissue and cartilage-pannus junction in patients with rheumatoid arthritis: implications for local actions of tumor necrosis factor alpha. Arthritis Rheum 1992 Oct; 35(10): 1170–8PubMedCrossRef
13.
go back to reference 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): 1041–5PubMedCrossRef 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): 1041–5PubMedCrossRef
14.
go back to reference 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): 211–20PubMedCrossRef 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): 211–20PubMedCrossRef
15.
go back to reference Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 1999; 130: 478–86PubMed Moreland LW, Schiff MH, Baumgartner SW, et al. Etanercept therapy in rheumatoid arthritis: a randomized, controlled trial. Ann Intern Med 1999; 130: 478–86PubMed
16.
go back to reference Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997 Jul; 337(3): 141–7PubMedCrossRef Moreland LW, Baumgartner SW, Schiff MH, et al. Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 1997 Jul; 337(3): 141–7PubMedCrossRef
17.
go back to reference 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; 342(11): 763–9PubMedCrossRef 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; 342(11): 763–9PubMedCrossRef
18.
go back to reference 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): 245–7PubMedCrossRef 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): 245–7PubMedCrossRef
19.
go back to reference Takei S, Groh D, Shaham B, et al. Safety and efficacy of high dose etanercept in the treatment of juvenile rheumatoid arthritis. Arthritis Rheum 2000; 43 Suppl.: S256 Takei S, Groh D, Shaham B, et al. Safety and efficacy of high dose etanercept in the treatment of juvenile rheumatoid arthritis. Arthritis Rheum 2000; 43 Suppl.: S256
20.
go back to reference Takei S, Groh D, Bernstein B, et al. Safety and efficacy of high dose etanercept in the treatment of juvenile rheumatoid arthritis. J Rheumatol 2001 Jul; 28(7): 1677–80PubMed Takei S, Groh D, Bernstein B, et al. Safety and efficacy of high dose etanercept in the treatment of juvenile rheumatoid arthritis. J Rheumatol 2001 Jul; 28(7): 1677–80PubMed
21.
go back to reference Rothman D, Smith K, Kimura Y. Safety and efficacy of etanercept (Enbrel®) in children with JRA less than 4 years of age [abstract]. Arthritis Rheum 2001; 44 Suppl.: 1435 Rothman D, Smith K, Kimura Y. Safety and efficacy of etanercept (Enbrel®) in children with JRA less than 4 years of age [abstract]. Arthritis Rheum 2001; 44 Suppl.: 1435
22.
go back to reference Prahalad S, Bove KE, Dickens D, et al. Etanercept in the treatment of macrophage activation syndrome [published erratum appears in J Rheumatol 2001 Oct; 28 (10): 2370]. J Rheumatol 2001; 28(9): 2120–4PubMed Prahalad S, Bove KE, Dickens D, et al. Etanercept in the treatment of macrophage activation syndrome [published erratum appears in J Rheumatol 2001 Oct; 28 (10): 2370]. J Rheumatol 2001; 28(9): 2120–4PubMed
23.
go back to reference Reiff A, Takei S, Sadeghi S, et al. Etanercept therapy in children with treatment-resistant uveitis. Arthritis Rheum 2001 Jun; 44(6): 1411–5PubMedCrossRef Reiff A, Takei S, Sadeghi S, et al. Etanercept therapy in children with treatment-resistant uveitis. Arthritis Rheum 2001 Jun; 44(6): 1411–5PubMedCrossRef
24.
go back to reference Reimold AM. New indications for treatment of chronic inflammation by TNF-alpha blockade. Am J Med Sci 2003 Feb; 325(2): 75–92PubMedCrossRef Reimold AM. New indications for treatment of chronic inflammation by TNF-alpha blockade. Am J Med Sci 2003 Feb; 325(2): 75–92PubMedCrossRef
25.
go back to reference Kimura Y, Pinho P, Higgins G, et al. Treatment of systemic onset juvenile rheumatoid arthritis (SOJRA) with etanercept: a follow-up study [abstract]. Arthritis Rheum 2002; 46 Suppl.: S481 Kimura Y, Pinho P, Higgins G, et al. Treatment of systemic onset juvenile rheumatoid arthritis (SOJRA) with etanercept: a follow-up study [abstract]. Arthritis Rheum 2002; 46 Suppl.: S481
26.
go back to reference Kimura Y, Li S, Ebner-Lyon L. Treatment of systemic JIA with etanercept: results of a survey [abstract]. Arthritis Rheum 2000; 43 Suppl.: 1142 Kimura Y, Li S, Ebner-Lyon L. Treatment of systemic JIA with etanercept: results of a survey [abstract]. Arthritis Rheum 2000; 43 Suppl.: 1142
27.
go back to reference Higgins G, Jones K, Rennebohm R. Variable response of systemic juvenile rheumatoid arthritis to etanercept [abstract]. Arthritis Rheum 2000; 43 Suppl.: S257 Higgins G, Jones K, Rennebohm R. Variable response of systemic juvenile rheumatoid arthritis to etanercept [abstract]. Arthritis Rheum 2000; 43 Suppl.: S257
28.
go back to reference Immunex Corporation. Enbrel® [package insert]. Seattle (WA): Immunex Corporation, 2004 Immunex Corporation. Enbrel® [package insert]. Seattle (WA): Immunex Corporation, 2004
29.
go back to reference Giannini EH, Lovell DJ, Felson DT, et al. Preliminary core set of outcome variables for use in JRA clinical trials. Arthritis Rheum 1994; 37 Suppl.: S428CrossRef Giannini EH, Lovell DJ, Felson DT, et al. Preliminary core set of outcome variables for use in JRA clinical trials. Arthritis Rheum 1994; 37 Suppl.: S428CrossRef
30.
go back to reference Giannini EH, Ruperto N, Ravelli A, et al. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997 Jul; 40(7): 1202–9PubMed Giannini EH, Ruperto N, Ravelli A, et al. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997 Jul; 40(7): 1202–9PubMed
31.
go back to reference Cassidy J, Petty R. Textbook of pediatric rheumatology. St Louis (MO): WB Saunders Company, 2001 Cassidy J, Petty R. Textbook of pediatric rheumatology. St Louis (MO): WB Saunders Company, 2001
32.
go back to reference 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): 228–9CrossRef 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): 228–9CrossRef
33.
go back to reference Russo RA, Katsicas MM, Zelazko M. Etanercept in systemic juvenile idiopathic arthritis. Clin Exp Rheumatol 2002 Sep–Oct; 20(5): 723–6PubMed Russo RA, Katsicas MM, Zelazko M. Etanercept in systemic juvenile idiopathic arthritis. Clin Exp Rheumatol 2002 Sep–Oct; 20(5): 723–6PubMed
34.
go back to reference 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): 410–2PubMedCrossRef 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): 410–2PubMedCrossRef
35.
go back to reference Horneff G, Foeldvari I, Kuster R, et al. Etanercept for the treatment of juvenile idiopathic arthritis: results of the German registry [abstract]. Ann Rheum Dis 2002; 61Suppl. 1: OP0062 Horneff G, Foeldvari I, Kuster R, et al. Etanercept for the treatment of juvenile idiopathic arthritis: results of the German registry [abstract]. Ann Rheum Dis 2002; 61Suppl. 1: OP0062
36.
go back to reference 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): 1093–101PubMedCrossRef 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): 1093–101PubMedCrossRef
37.
go back to reference Husni ME, Maier AL, Mease PJ, et al. Etanercept in the treatment of adult patients with Still’s disease. Arthritis Rheum 2002 May; 46(5): 1171–6PubMedCrossRef Husni ME, Maier AL, Mease PJ, et al. Etanercept in the treatment of adult patients with Still’s disease. Arthritis Rheum 2002 May; 46(5): 1171–6PubMedCrossRef
38.
go back to reference Sicotte NL, Voskuhl RR. Onset of multiple sclerosis associated with anti-TNF therapy. Neurology 2001 Nov 27; 57(10): 1885–8PubMedCrossRef Sicotte NL, Voskuhl RR. Onset of multiple sclerosis associated with anti-TNF therapy. Neurology 2001 Nov 27; 57(10): 1885–8PubMedCrossRef
39.
go back to reference Gardam MA, Keystone EC, Menzies R, et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003 Mar; 3(3): 148–55PubMedCrossRef Gardam MA, Keystone EC, Menzies R, et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003 Mar; 3(3): 148–55PubMedCrossRef
40.
go back to reference St Clair EW. Infliximab treatment for rheumatic disease: clinical and radiological efficacy. Ann Rheum Dis 2002; 61Suppl. 2: ii67–9PubMed St Clair EW. Infliximab treatment for rheumatic disease: clinical and radiological efficacy. Ann Rheum Dis 2002; 61Suppl. 2: ii67–9PubMed
41.
go back to reference Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001 Oct 11; 345(15): 1098–104PubMedCrossRef Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001 Oct 11; 345(15): 1098–104PubMedCrossRef
42.
go back to reference Shergy W, Phillips R, Hunt R, et al. Safety and efficacy of infliximab therapy after etanercept failure [abstract]. Arthritis Rheum 2001; 44 Suppl.: 174 Shergy W, Phillips R, Hunt R, et al. Safety and efficacy of infliximab therapy after etanercept failure [abstract]. Arthritis Rheum 2001; 44 Suppl.: 174
43.
go back to reference Gerloni V, Pontikaki I, Desiati F, et al. Infliximab in the treatment of persistently active refractory juvenile idiopathic (chronic) arthritis: a short term pilot study [abstract]. Arthritis Rheum 2000; 43 Suppl.: 1139 Gerloni V, Pontikaki I, Desiati F, et al. Infliximab in the treatment of persistently active refractory juvenile idiopathic (chronic) arthritis: a short term pilot study [abstract]. Arthritis Rheum 2000; 43 Suppl.: 1139
44.
go back to reference Masatlioglu S, Gogus F, Cevrigen D, et al. Infliximab in the treatment of refractory juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2002; 46 Suppl.: 1276 Masatlioglu S, Gogus F, Cevrigen D, et al. Infliximab in the treatment of refractory juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2002; 46 Suppl.: 1276
45.
go back to reference Honkanen V, Tynjala P, Vahasalo P, et al. Infliximab in juvenile arthritis: 1-year follow-up [abstract]. Arthritis Rheum 2002; 46 Suppl.: 1272 Honkanen V, Tynjala P, Vahasalo P, et al. Infliximab in juvenile arthritis: 1-year follow-up [abstract]. Arthritis Rheum 2002; 46 Suppl.: 1272
46.
go back to reference Kimura Y, Imundo L, Li S. High dose infliximab in the treatment of resistant systemic juvenile rheumatoid arthritis [abstract]. Arthritis Rheum 2001; 44 Suppl.: 1316 Kimura Y, Imundo L, Li S. High dose infliximab in the treatment of resistant systemic juvenile rheumatoid arthritis [abstract]. Arthritis Rheum 2001; 44 Suppl.: 1316
47.
go back to reference Vougiouka O, Rizou S, Grafakou O, et al. Infliximab and etanercept in the treatment of juvenile idiopathic arthritis: the Athens experience [abstract]. Ann Rheum Dis 2001; 60 Suppl. ii: P176 Vougiouka O, Rizou S, Grafakou O, et al. Infliximab and etanercept in the treatment of juvenile idiopathic arthritis: the Athens experience [abstract]. Ann Rheum Dis 2001; 60 Suppl. ii: P176
48.
go back to reference Kanakoudi-Tsakalidou F, Trachana M, Pratsidou-Gertsi P, et al. Safety and efficacy of two anti-TNF preparations (etanercept and infliximab) in patients with JIA resistant to conventional therapeutic regimens [abstract]. Ann Rheum Dis 2001; 60 Suppl. ii: V4.1 Kanakoudi-Tsakalidou F, Trachana M, Pratsidou-Gertsi P, et al. Safety and efficacy of two anti-TNF preparations (etanercept and infliximab) in patients with JIA resistant to conventional therapeutic regimens [abstract]. Ann Rheum Dis 2001; 60 Suppl. ii: V4.1
49.
go back to reference Mohan N, Edwards ET, Cupps TR, et al. Demyelination occurring during antitumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 2001 Dec; 44(12): 2862–9PubMedCrossRef Mohan N, Edwards ET, Cupps TR, et al. Demyelination occurring during antitumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 2001 Dec; 44(12): 2862–9PubMedCrossRef
50.
go back to reference Brown SL, Greene MH, Gershon SK, et al. Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration. Arthritis Rheum 2002 Dec; 46(12): 3151–8PubMedCrossRef Brown SL, Greene MH, Gershon SK, et al. Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration. Arthritis Rheum 2002 Dec; 46(12): 3151–8PubMedCrossRef
51.
go back to reference Kramer N, Chuzhin Y, Kaufman LD, et al. Methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid arthritis. Arthritis Rheum 2002 Dec 15; 47(6): 670–1PubMedCrossRef Kramer N, Chuzhin Y, Kaufman LD, et al. Methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid arthritis. Arthritis Rheum 2002 Dec 15; 47(6): 670–1PubMedCrossRef
52.
go back to reference Marchesoni A, Arreghini M, Panni B, et al. Life-threatening reversible bone marrow toxicity in a rheumatoid arthritis patient switched from leflunomide to infliximab. Rheumatology (Oxford) 2003 Jan; 42(1): 193–4CrossRef Marchesoni A, Arreghini M, Panni B, et al. Life-threatening reversible bone marrow toxicity in a rheumatoid arthritis patient switched from leflunomide to infliximab. Rheumatology (Oxford) 2003 Jan; 42(1): 193–4CrossRef
53.
go back to reference Salmon D. Recommendations about the prevention and management of tuberculosis in patients taking infliximab. Joint Bone Spine 2002 Mar; 69(2): 170–2PubMedCrossRef Salmon D. Recommendations about the prevention and management of tuberculosis in patients taking infliximab. Joint Bone Spine 2002 Mar; 69(2): 170–2PubMedCrossRef
54.
go back to reference Cohen S, Hurd E, Cush J, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, doubleblind, placebo-controlled trial. Arthritis Rheum 2002 Mar; 46(3): 614–24PubMedCrossRef Cohen S, Hurd E, Cush J, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, doubleblind, placebo-controlled trial. Arthritis Rheum 2002 Mar; 46(3): 614–24PubMedCrossRef
55.
go back to reference Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology (Oxford) 2002 Sep; 41(9): 972–80CrossRef Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology (Oxford) 2002 Sep; 41(9): 972–80CrossRef
56.
go back to reference Nuki G, Bresnihan B, Bear MB, et al. Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human in-terleukin-1 receptor antagonist) in patients with rheumatoid arthritis: extension phase of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002 Nov; 46(11): 2838–46PubMedCrossRef Nuki G, Bresnihan B, Bear MB, et al. Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human in-terleukin-1 receptor antagonist) in patients with rheumatoid arthritis: extension phase of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2002 Nov; 46(11): 2838–46PubMedCrossRef
57.
go back to reference Bresnihan B. The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoid arthritis. Semin Arthritis Rheum 2001 Apr; 30(5 Suppl. 2): 17–20PubMedCrossRef Bresnihan B. The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoid arthritis. Semin Arthritis Rheum 2001 Apr; 30(5 Suppl. 2): 17–20PubMedCrossRef
58.
go back to reference Muzaffer MA, Dayer JM, Feldman BM, et al. Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis. J Rheumatol 2002 May; 29(5): 1071–8PubMed Muzaffer MA, Dayer JM, Feldman BM, et al. Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis. J Rheumatol 2002 May; 29(5): 1071–8PubMed
59.
go back to reference Andrias R, Porras O, Rudge S, et al. Preliminary data from a study of kineret (anakinra) in children with juvenile rheumatoid arthritis [abstract]. Arthritis Rheum 2002; 46 Suppl.: 496 Andrias R, Porras O, Rudge S, et al. Preliminary data from a study of kineret (anakinra) in children with juvenile rheumatoid arthritis [abstract]. Arthritis Rheum 2002; 46 Suppl.: 496
60.
go back to reference Nishimoto N, Kishimoto T, Yoshizaki K. Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann Rheum Dis 2000; 59Suppl. 1: i21–7PubMedCrossRef Nishimoto N, Kishimoto T, Yoshizaki K. Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann Rheum Dis 2000; 59Suppl. 1: i21–7PubMedCrossRef
61.
go back to reference Choy EH, Isenberg DA, Garrood T, et al. Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum 2002 Dec; 46(12): 3143–50PubMedCrossRef Choy EH, Isenberg DA, Garrood T, et al. Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum 2002 Dec; 46(12): 3143–50PubMedCrossRef
62.
go back to reference Yilmaz M, Kendirli SG, Altintas D, et al. Cytokine levels in serum of patients with juvenile rheumatoid arthritis. Clin Rheumatol 2001; 20(1): 30–5PubMedCrossRef Yilmaz M, Kendirli SG, Altintas D, et al. Cytokine levels in serum of patients with juvenile rheumatoid arthritis. Clin Rheumatol 2001; 20(1): 30–5PubMedCrossRef
63.
go back to reference De Benedetti F, Pignatti P, Gerloni V, et al. Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis. J Rheumatol 1997 Jul; 24(7): 1403–9PubMed De Benedetti F, Pignatti P, Gerloni V, et al. Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis. J Rheumatol 1997 Jul; 24(7): 1403–9PubMed
64.
go back to reference De Benedetti F, Massa M, Pignatti P, et al. Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 1994 May; 93(5): 2114–9PubMedCrossRef De Benedetti F, Massa M, Pignatti P, et al. Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 1994 May; 93(5): 2114–9PubMedCrossRef
65.
go back to reference Pignatti P, Vivarelli M, Meazza C, et al. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J Rheumatol 2001 Jul; 28(7): 1670–6PubMed Pignatti P, Vivarelli M, Meazza C, et al. Abnormal regulation of interleukin 6 in systemic juvenile idiopathic arthritis. J Rheumatol 2001 Jul; 28(7): 1670–6PubMed
66.
go back to reference Wendling D, Racadot E, Wijdenes J. Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody. J Rheumatol 1993 Feb; 20(2): 259–62PubMed Wendling D, Racadot E, Wijdenes J. Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody. J Rheumatol 1993 Feb; 20(2): 259–62PubMed
67.
go back to reference Yokota S, Miyamae T, Imagawa T, et al. Therapeutic efficacy of humanized anti-IL-6-receptor antibody in systemic juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2001; 44 Suppl.: 1432 Yokota S, Miyamae T, Imagawa T, et al. Therapeutic efficacy of humanized anti-IL-6-receptor antibody in systemic juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2001; 44 Suppl.: 1432
68.
go back to reference Yokota S, Miyamae T, Imagawa T, et al. Long-term therapeutic efficacy of humanized anti-IL-6-receptor antibody for systemic juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2002; 46 Suppl.: 1270CrossRef Yokota S, Miyamae T, Imagawa T, et al. Long-term therapeutic efficacy of humanized anti-IL-6-receptor antibody for systemic juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2002; 46 Suppl.: 1270CrossRef
69.
go back to reference Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998 Sep; 41(9): 1552–63PubMedCrossRef Maini RN, Breedveld FC, Kalden JR, et al. Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998 Sep; 41(9): 1552–63PubMedCrossRef
70.
go back to reference Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human antitumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003 Jan; 48(1): 35–45PubMedCrossRef Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human antitumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 2003 Jan; 48(1): 35–45PubMedCrossRef
71.
go back to reference Hashkes PJ, Balistreri WF, Bove KE, et al. The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis. Arthritis Rheum 1997 Dec; 40(12): 2226–34PubMedCrossRef Hashkes PJ, Balistreri WF, Bove KE, et al. The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis. Arthritis Rheum 1997 Dec; 40(12): 2226–34PubMedCrossRef
72.
go back to reference Hashkes PJ, Balistreri WF, Bove KE, et al. The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis. J Pediatr 1999 Jan; 134(1): 47–52PubMedCrossRef Hashkes PJ, Balistreri WF, Bove KE, et al. The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis. J Pediatr 1999 Jan; 134(1): 47–52PubMedCrossRef
Metadata
Title
Biologic Agents for the Treatment of Juvenile Rheumatoid Arthritis
Current Status
Authors
Ruy Carrasco
Judith A. Smith
Professor Daniel Lovell
Publication date
01-05-2004
Publisher
Springer International Publishing
Published in
Pediatric Drugs / Issue 3/2004
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI
https://doi.org/10.2165/00148581-200406030-00001