Anakinra - eine neue therapeutische Option für die systemische juvenile idiopathische Arthritis

Zusammenfassung

Die systemische juvenile idiopathische Arthritis (SJIA), charakterisiert durch eine Arthritis, intermittierendes Fieber, flüchtiges Exanthem, generalisierte Lymphknotenschwellungen, Hepatosplenomegalie und Serositis, ist eine schwer verlaufende Erkrankung im Kindes- und Jugendalter. Antirheumatische Medikamente, die sich bei anderen Formen der JIA bewährt haben, weisen überwiegend nur eine begrenzte Wirkung auf. Dem proinflammatorische Zytokin Interleukin-1 (IL-1) konnte in der Pathogenese der SJIA eine bedeutende Rolle zugewiesen werden, was die Möglichkeit eines Einsatzes des IL-1-Rezeptorantagonisten Anakinra nahelegte. Dieses scheint sich nach den bislang vorliegenden, vorläufigen, auch eigenen Beobachtungen in begrenztem Umfang zu bestätigen. Ein wichtiger Faktor für einen Therapieerfolg scheint die Patientenauswahl zu sein. Kontrollierte Studien fehlen bislang.

Abstract

Systemic juvenile idiopathic arthritis (SJIA) is a severe disease of childhood characterized manifested by arthritis, fever, rash, generalized lymph node swelling, hepatosplenomegaly and serositis. Antirheumatic drugs show only limited effects, although they are effective for other forms of JIA. The proinflammatoric cytokine interleukin-1 (IL-1) seems to play an important role in the pathogenesis of SJIA. Therefore, it seemed reasonable to use the IL-1 receptor antagonist Anakinra in treatment of SJIA. International experiences up to now including our own results confirm a sometimes amazing efficacy of Anakinra in SJIA. An important requirement for reliable results, however, concerns the selection of patients eligible for the treatment. Controlled studies are still missing.

Schlüsselwörter

systemische juvenile idiopathische Arthritis - Anakinra - Interleukin-1

Key words

systemic juvenile idiopathic arthritis - anakinra - interleukin-1

Literatur

• 1 Adams A, Lehman T. Update on the pathogenesis and treatment of systemic onset juvenile rheumatoid arthritis.  Curr Opin Rheumatol. 2005;  17 612-616
• 2 Andersson G, Fasth A, Andersson J. Incidence and prevalence of juvenile rheumatoid arthritis: a population survey.  Ann Rheum dis. 1987;  46 277-281
• 3 Bowyer S, Roettcher P, Higgins C. et al . Health status of patients with juvenile rheumatoid arthritis at 1 and 5 years after diagnosis.  J Rheumatol. 2003;  30 394-400
• 4 Breshnihan B, Alvaro-Gracia J, Cobby M. et al . Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.  Arthritis Rheum. 1998;  41 2196
• 5 Calvo I, Lopez Montesenios M B, Millan M. Anakinra effectivity in systemic juvenile idiopathic arthritis non responding to conventional treatments. PRES 2005.  Clin Exp Rheumatol. 2005;  23 (Suppl 37) S 66
• 6 De Benedetti F, Pignatti P, Massa M. et al . Circulating levels of interleukin 1β and of interleukin 1 receptor antagonist in systemic juvenile chronic arthritis.  Clin Exp Rheumatol. 1995;  13 779-784
• 7 De Benedetti F, Pignatti P, Gerloni V. et al . Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis.  J Rheumatol. 1997;  24 1403-1409
• 8 Dayer J. Evidence for the biological modulation of IL-1 activity: The role of IL1-Ra.  Clin Exp Rheumatol. 2002;  20 (Suppl 27) S14-S20
• 9 Genovese M, Cohen S, Moreland L. et al . Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate.  Arthritis Rheum. 2004;  50 1412-1419
• 10 Goldbacher-Mansky R, Dailey N, Canna S. et al . Neonatal-onset multisystem inflammatory disease responsive to interleukin-1β inhibition.  N Engl J Med. 2006;  355 581-592
• 11 Hawkins P, Lachmann H, Aganna E. et al . Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra.  Arthritis Rheum. 2004;  50 607-612
• 12 Henrickson M. Efficacy of anakinra in systemic arthritis.  Arthritis Rheum. 2004;  50 (Suppl) S 438
• 13 Horneff G, Schmeling H, Biedermann T. et al . The german etanercept registry for treatment of juvenile idiopathic arthritis.  Ann Rheum Dis. 2004;  63 1638-1644
• 14 Irigoyen P, Olson J, Hom C. et al . Treatment of systemic onset juvenile idiopathic arthritis with anakinra.  Pediatric Rheumatology Online Journal. 2006;  2
• 15 Kimura Y, Pinho P, Walco G. et al . Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis.  J Rheumatol. 2005;  32 935-942
• 16 Kropp A, Kettner H, Michels M. Anakinra bei zwei Kindern mit therapieresistenter systemischer juveniler idiopathischer Arthritis.  Arthritis + Rheuma. 2006;  26 109-112
• 17 Lomater C, Gerloni V, Gattinara M. et al . Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years.  J Rheumatol. 2000;  27 491-496
• 18 Lovell D, Giannini E, Reiff A. et al . Etanercept in children with polyarticular juvenile rheumatoid arthritis.  N Engl J Med. 2000;  342 763-769
• 19 Lovell D, Bowyer S, Solinger A. Interleukin-1 blockade by anakinra improves clinical symptoms in patients with neonatal-onset multisystem inflammatory disease.  Arthritis Rheum. 2005;  52 1283-1286
• 20 Mangge H, Kenzian H, Gallistl S. et al . Serum cytokines in juvenile rheumatoid arthritis.  Arthritis Rheum. 1995;  38 211-220
• 21 Modesto C, Saiz E, Galvez J. et al . Il-1Ra treatment in systemic onset juvenile idiopathic arthritis. Clinical and biological response. PRES 2005.  Clin Exp Rheumatol. 2005;  23 (Suppl 37) S 67
• 22 Muzaffer M, Dayer J, Feldman B. 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;  29 1071-1078
• 23 Pascual V, Allantaz F, Arce E. et al . Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade.  JEM. 2005;  201 1479-1486
• 24 Petty R E, Cassidy J T. Systemic arthritis. Cassidy JT, Petty RE, Laxer R, Lindsley CB Textbook of Pediatric Rheumatology Philadelphia; Elsevier Saunders 2005 5. Edition: 291-303
• 25 Petty R E, Southwood T R, Manners P. et al . International League of Association for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton 2001.  J Rheumatol. 2004;  31 390-392
• 26 Quartier P, Kone-Paut I, Job-Deslandre C. et al . Il-1Ra (anakinra) treatment in systemic-onset juvenile idiopathic arthritis. PRES 2005.  Clin Exp Rheumatol. 2005;  23 (Suppl 37) S 65
• 27 Ravelli A. Macrophage activation syndrome.  Curr Opin Rheumatol. 2002;  14 548-552
• 28 Reiff A. The use of anakinra in juvenile arthritis.  Current Rheumatology Reports. 2005;  7 434-440
• 29 Rooney M, David J, Symons J. et al . Inflammatory cytokine responses in juvenile chronic arthritis.  Br J Rheumatol. 1995;  34 454-460
• 30 Rubbert-Roth A, Perniok A. Der Interleukin-1-Rezeptorantagonist Anakinra (Kineret®) in der Behandlung mit rheumatoider Arthritis.  Z Rheumatol. 2003;  62 367-377
• 31 Saadeh C, Hollister R, Malacara J. et al . Successful treatment of stills disease with anakinra after failure to respond to multiple therapeutic modalities including methotrexate, infliximab, intravenous immunoglobulines, etanercept and adalinumab.  Ann Rheum Dis. 2004;  S1 63
• 32 Spiegel R, Schneider R, Lang B. et al . Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis. A multicenter corhort study.  Arthritis Rheum. 2000;  43 2402-2409
• 33 Svantesson H, Akesson A, Eberhardt K. et al . Prognosis in juvenile rheumatoid arthritis with systemic onset. A follow-up study.  Scand J Rheumatol. 1983;  12 139
• 34 Waugh J, Perry C M. Anakinra: a review of its use in the management of rheumatoid arthritis.  Biodrugs. 2005;  19 189-202
• 35 Woo P, Southwood T, Prieur A. et al . Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoartikulär or systemic arthritis.  Arthritis Rheum. 2000;  43 1849-1857
• 36 Verbsky J, White A. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis.  J Rheumatol. 2004;  31 2071-2075
• 37 Yilmaz M, Kendirli G, Altintas D. et al . Cytokine levels in serum of patients with juvenile rheumatoid arthritis.  Clin Rheumatol. 2001;  20 30-35