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Arthritis und Rheuma 2011; 31(05): 334-342
DOI: 10.1055/s-0037-1618085
Kinder-rheumatologie: Übersichtsbeitrag
Schattauer GmbH

Zehn Jahre Erfahrung im deutschen JIA-Etanercept-Register

Lehren aus wechselnden Patientenpopulationen10 years experience in the German JIA Etanercept Registrylessons from changing patient populations
G. Horneff
1   Kinderrheumazentrum Sankt Augustin, Asklepios Klinik, Sankt Augustin
,
I. Foeldvari
2   Hamburger Zentrum für pädiatrische Rheumatologie, Hamburg
,
K. Minden
3   Charité – Universitätsmedizin Berlin, Campus Mitte
,
G. Ganser
4   St. Josef-Stift Sendenhorst
,
J.-P. Haas
5   Deutsches Zentrum für Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen
,
A. Hospach
6   Olgahospital, Stuttgart
,
H.-I. Huppertz
7   Prof.-Hess-Kinderklinik, Bremen
› Author Affiliations
Further Information

Publication History

Publication Date:
26 December 2017 (online)

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Zusammenfassung

Hintergrund: Seit Einführung der TNF-Inhibitoren in die Therapie der juvenilen idiopathischen Arthritis (JIA) hat sich die Prognose für viele Patienten erheblich verbessert.

Ziele und Methoden: Daten des deutschen JIA-Etanercept-Registers wurden in Jahreskohorten von 2000–2010 bzgl. Patientencharakteristika, Vorbehandlung, Begleittherapie und Krankheitsaktivität analysiert. Die Wirksamkeit der Therapie wurde anhand der PedACR30/50/70-Kriterien und Kriterien für inaktive Erkrankung und Remission analysiert. Sicherheitsbewertungen erfolgten auf der Basis von Berichten über unerwünschte Ereignisse.

Ergebnisse: Von 2000 bis 2010 wurden 1335 mit Etanercept behandelte JIA-Patienten in das Register aufgenommen. Am häufigsten erhielten Patienten mit einer seronegativen Polyarthritis Etanercept. In den frühen Jahreskohorten lag der Anteil von Patienten mit einer systemischen JIA bei 26 %, zuletzt zwischen zwei und fünf Prozent. Demgegenüber stieg der Anteil von Patienten mit einer Enthesitis-assoziierten Arthritis von zwei Prozent auf 17 % an. Die initial aufgenommenen Patienten wurden zuvor mit zahlreichen Antirheumatika (Mittel 3,4) einschließlich Zytostatika vorbehandelt. Diese Anzahl reduzierte sich über die Jahre auf 1,3/Patient. In der initialen Patientenkohorte wurden Kortikosteroide bei 83 %, Methotrexat bei 95 % und andere DMARDs bei 45 % der Patienten begleitend eingesetzt. Diese Begleitmedikation verminderte sich bei der Patientenkohorte mit Behandlungsbeginn in 2010 auf 27 %, 67 % und zehn Prozent. Die mittlere Krankheitsdauer vor Behandlungsbeginn nahm von 6,1 Jahren (Median 4,5 Jahre) auf 3,4 Jahre (Median 1,9 Jahre) ab. Der Anteil der Patienten mit einem PedACR70-Score nach Abschluss der ersten zwölf Behandlungsmonate stieg von 57 % auf 74 % an. Eine inaktive Erkrankung innerhalb eines Jahres wurde bei 24 % der initialen Patientenkohorte dokumentiert, während sich diese Rate im Beobachtungsverlauf auf 54 % erhöhte. Die Gesamtzahl unerwünschter Ereignisse im ersten Jahr der Behandlung war konstant, während die Rate schwerwiegender unerwünschter Ereignisse von 0,13/Patient auf 0,02/Patient sank.

Fazit: Bei JIA-Patienten wird eine Therapie mit Etanercept zunehmend früher begonnen. Es erfolgen weniger Vorbehandlungen und es werden weniger Medikamente begleitend eingesetzt. Dabei zeigt sich eine verbesserte Verträglichkeit mit weniger ernsthaften Nebenwirkungen und eine höhere Effektivität.

Summary

Background: Within the last decade treatment of JIA with etanercept has become a valuable option changing outcome perspective for patients with previously refractory arthritis.

Objectives and methods: To report on a broad population of JIA patients documented in the German Registry with analysis of pretreatment, concomitant treatment and disease activity parameters and outcome. Efficacy was assessed using the PedACR30/50 and 70 criteria and the proposed criteria for inactive disease and remission on medication. Safety assessments were based on adverse events reports.

Results: Since 2000 1335 JIA patients have been enrolled in the German JIA Etanercept registry. At start of the registry 26 % of patients belonged to the soJIA category, this quote decreased to 2 %, while the quote of patients with enthesitis-related arthritis increased from 2 % to 17 %. While initially patients had been pretreated with numerous antirheumatic agents, including cytotoxic agents, pre-treatment markedly decreased from a mean of 3.4 to 1.3 DMARDs/patient. There was a marked reduction of concomitant treatment as well. Concomitant treatment initially consisted of corticosteroids in 83 %, methotrexate in 95 % and other DMARDs in 45 % of patients, while in patients starting treatment in 2010 these numbers decreased to 27 %, 67 % and 10 %, respectively. Moreover, the disease duration before treatment decreased from 6.1 to 3.4 (mean) years (median 4.5 to 1.9 years). In consequence of these changes, the number of patients reaching a PedACR70 response after the first 12 months of treatment increased from 57 % to 74 % of patients. Inactive disease within one year was documented initially in 24 % of patients while this rate increased to 53 %. While the total number of adverse events in the first year of treatment remained unchanged, the rate of serious adverse events decreased from 0.13/pat. to 0.02/pat.

Conclusion: These data indicate that patients starting etanercept within recent years had been treated earlier with etanercept, received less pre-treatment and less concomitant treatment with corticosteroids as well as DMARDs. In contrast they had a better outcome regarding the number of patients reaching a PedACR70 and “inactive disease” after 1 year of treatment. They also experienced less serious adverse events. During a 10 year period an earlier start and a better pre selection of patients led to an improved outcome.

Schlüsselwörter

Juvenile idiopathische Arthritis - TNF-Inhibitoren - JIA-Etanercept-Register - Therapiewirksamkeit - Therapieverträglichkeit

Keywords

Juvenile idiopathische Arthritis - TNF-inhibitors - German JIA Etanercept registry - drug efficacy - drug safety
 

  • Literatur

  • 1 Armbrust W, Kamphuis SS, Wolfs TW. et al. Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology 2004; 43: 527-529.
    CrossrefPubMedGoogle Scholar
  • 2 Biester S, Deuter C, Michels H. et al. Adalimumab in the Therapy of Uveitis in Childhood. Br J Ophthalmol 2007; 91: 319-324 Epub 2006 Oct 11.
    CrossrefPubMedGoogle Scholar
  • 3 Flato B, Aasland A, Vinje O, Forre O. Outcome and predictive factors in juvenile rheumatoid arthritis and juvenile spondylarthropathy. J Rheumatol 1998; 25: 366-375.
    Google Scholar
  • 4 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; 52: 548-553.
    CrossrefPubMedGoogle Scholar
  • 5 Giannini EH, Brewer Jr EJ, Kuzmina N. et al. Auranofin in the treatment of juvenile rheumatoide arthritis. Results of the USA-USSR double blind, placebo-controlled trial. The USA Pediatric Rheumatology Collaborative Study Group. The USSR Cooperative Children's Study group. Arthritis Rheum 1990; 33: 466-476.
    CrossrefPubMedGoogle Scholar
  • 6 Guellac N, Niehues T. Interdisciplinary and evidence-base treatment guidelines for juvenile idiopathic arthritis. Klin padiatr 2008; 220: 392-402.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 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; 68: 519-525.
    CrossrefPubMedGoogle Scholar
  • 8 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; 48: 916-919.
    CrossrefPubMedGoogle Scholar
  • 9 Horneff G, Schmeling H, Biedermann T. et al. The German Etanercept Registry for Treatment of Juvenile Idiopathic Arthritis (JIA). Ann Rheum Dis 2004; 63: 1638-1644.
    CrossrefPubMedGoogle Scholar
  • 10 Horneff G. Einsatz von Biologika bei der juvenilen idiopathischen Arthritis. Konsensusstatement des 7. Wörlitzer Expertengespräches 2004 für die Arbeitsgemeinschaft Kinder- und Jugendrheumatologie. Monatsschr Kinderheilkd 2005; 153: 473-479.
    CrossrefGoogle Scholar
  • 11 Horneff G. Juvenile Arthritiden. Z Rheumatol 2010; 69: 719-735.
    CrossrefPubMedGoogle Scholar
  • 12 Horneff G, Foeldvari I, Minden K. et al. Report on Malignancies in the German Juvenile Idiopathic Arthritis Registry. Rheumatol (Oxford) 2011; 50: 230-236.
    CrossrefPubMedGoogle Scholar
  • 13 Ilowite N, Porras O, Reiff A. et al. Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study. Clin Rheumatol 2009; 28: 129-137 Epub 2008 Sep 3.
    CrossrefPubMedGoogle Scholar
  • 14 Kahn P, Weiss M, Imundo LF, Levy DM. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 2006; 5 (864) e1-e2.
    Google Scholar
  • 15 Klein A, Horneff G. Treatment strategies for juvenile idiopathic arthritis. Expert Opin Pharmacother 2009; 10: 3049-3060.
    CrossrefPubMedGoogle Scholar
  • 16 Kuemmerle-Deschner JB, Horneff G. Safety and efficacy of once-weekly application of Etanercept in children with juvenile idiopathic arthritis. Rheumatol Int 2007; 28: 153-156.
    CrossrefPubMedGoogle Scholar
  • 17 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; 62: 245-247.
    CrossrefPubMedGoogle Scholar
  • 18 Lovell Dj, Giannini EH, Reiff A. et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med 2000; 342: 763-769.
    CrossrefPubMedGoogle Scholar
  • 19 Lovell DJ, Reiff A, Ilowite NT. et al Pediatric Rheumatology Collaborative Study Group.Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum 2008; 58: 1496-1504.
    CrossrefPubMedGoogle Scholar
  • 20 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; 54: 1987-1994.
    CrossrefPubMedGoogle Scholar
  • 21 Lovell DJ, Ruperto N, Goodman S. et al; Pediatric Rheumatology Collaborative Study Group; Pediatric Rheumatology International Trials Organisation. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med 2008; 359: 810-820.
    CrossrefPubMedGoogle Scholar
  • 22 Minden K, Niewerth M, Listing J. et al. Long-term outcome in patients with juvenile idiopathic arthritis. Arthritis Rheum 2002; 46: 2392-2401.
    CrossrefPubMedGoogle Scholar
  • 23 Papsdorf V, Horneff G. Complete control of disease activity and remission induced by treatment with etanercept in juvenile idiopathic arthritis. Rheumatol (Oxford) 2011; 50: 214-221.
    CrossrefPubMedGoogle Scholar
  • 24 Petty RE. Prognosis in children with rheumatic diseases: justification for consideration of new therapies. Rheumatology 1999; 38: 739-742.
    CrossrefPubMedGoogle Scholar
  • 25 Petty RE, Southwood TR, Baum J. et al. Revision of the proposed criteria for juvenile idiopathic arthritis: Durban 1997. J Rheumatol 1998; 25: 1991-1994.
    Google Scholar
  • 26 Prince FH, Twilt M, Jansen-Wijngaarden NC, van Suijlekom-Smit LW. Effectiveness of a once weekly double dose of etanercept in patients with juvenile idiopathic arthritis: a clinical study. Ann Rheum Dis 2007; 66: 704-705.
    CrossrefPubMedGoogle Scholar
  • 27 Quartier P, Allantaz F, Cimaz R. et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011; 70: 747-754. Epub 2010 Dec 20.
    CrossrefPubMedGoogle Scholar
  • 28 Ruperto N, Lovell DJ, Cuttica R. et al; Paediatric Rheumatology International Trials Organisation; Pediatric Rheumatology Collaborative Study Group: A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 2007; 56: 3096-3106.
    CrossrefPubMedGoogle Scholar
  • 29 Ruperto N, Lovell DJ, Quartier P. et al; Paediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet 2008; 372 (9636) 383-391. [Epub 2008 Jul 14].
    CrossrefPubMedGoogle Scholar
  • 30 Simonini G, Zannin ME, Caputo R. et al. Loss of efficacy during long-term infliximab therapy for sight-threatening childhood Uveitis. Rheumatology 2008; 47: 1510-1514.
    CrossrefPubMedGoogle Scholar
  • 31 Smith JA, Thompson DJS, 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; 53: 18-23.
    CrossrefPubMedGoogle Scholar
  • 32 Smolen JS, Beaulieu A, Rubbert-Roth A. et al; OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008; 371 (9617) 987-997.
    CrossrefPubMedGoogle Scholar
  • 33 Tynjälä P, Kotaniemi K, Lindahl P. et al. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford) 2008; 47: 339-344 [Epub 2008 Jan 31].
    PubMedGoogle Scholar
  • 34 Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr 2006; 4: 572-575.
    Google Scholar
  • 35 Woo P, Southwood TR, Prieur AM. et al. Randomized, placebocontrolled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systematic arthritis. Arthritis Rheum 2005; 43: 1849-1857.
    Google Scholar
  • 36 Wallace CA, Ruperto N, Giannini E. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004; 31: 2290-2294.
    Google Scholar
  • 37 Yokota S, Imagawa T, Mori M. et al. Efficacy and safety of tocilizumab in patients with systemiconset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 2008; 371 (9617) 998-1006.
    CrossrefPubMedGoogle Scholar
  • 38 Yokota S, Miyamae T, Imagawa T. et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemiconset juvenile idiopathic arthritis. Arthritis Rheum 2005; 52: 818-825.
    CrossrefPubMedGoogle Scholar