Zeitschrift für Rheumatologie

, Volume 69, Issue 6, pp 516–526 | Cite as

Malignome und Tumor-Nekrose-Faktor-Inhibitoren bei der juvenilen idiopathischen Arthritis

Leitthema

Zusammenfassung

Einleitung

Die Berichte über maligne Erkrankungen bei Tumor-Nekrose-Faktor- (TNF-)Hemmern-exponierten Kindern und Jugendlichen werfen Fragen nach einem möglicherweise erhöhten Risiko vor allem für Lymphome auf. Bisher ist die Zahl der mit Biologika behandelten Patienten mit einer juvenilen idiopathischen Arthritis (JIA) gering. Darüber hinaus ist das Wissen über die Hintergrundinzidenz von malignen Erkrankungen bei Kindern mit JIA und die Bedeutung der Komedikation begrenzt.

Ergebnis

Von 2001 bis 2009 wurden von über 1200 Patienten im deutschen JIA-Etanercept-Kinderregister 5 Fälle von bösartigen Erkrankungen dokumentiert: Non-Hodgkin-Lymphom, Hodgkin-Lymphom, Schilddrüsenkarzinom, Dottersackkarzinom und Zervixdysplasie. Alle Patienten wurden vor Therapie mit TNF-Hemmern mit einer Reihe von weiteren Medikamenten behandelt, einschließlich Immunsuppressiva. Alle Patienten hatten Etanercept erhalten, 2 Patienten waren zudem mit Adalimumab oder Infliximab behandelt. Malignome traten nach einer Therapiedauer mit Etanercept von 3 Wochen bis über 6 Jahre auf. Bei Auftreten der Tumorerkrankung hatten 3 Patienten noch Etanercept erhalten, 5 Methotrexat und einer Infliximab. Drei Malignome traten erst im Erwachsenenalter auf. Alle Patienten erholten sich.

Fazit

Diese Fallserie zeigt, dass bei JIA-Patienten die Indikation für Biologika sehr sorgfältig gestellt werden muss und die Patienten eine langfristige Beobachtung benötigen, die im Erwachsenenalter fortgesetzt werden muss. Obwohl es sich bisher um die Beschreibung einer zeitlichen Assoziation handelt, kann ein kausaler Zusammenhang nicht ausgeschlossen werden, und die Eltern/der Patient müssen hierüber angemessen aufgeklärt werden.

Schlüsselworte

Etanercept Adalimumab Infliximab Juvenile idiopathische Arthritis Malignome 

Malignancy and tumor necrosis factor inhibitors in juvenile idiopathic arthritis

Abstract

Introduction

Reports on malignancies observed in children exposed to TNF-inhibitors have raised questions about a potentially increased risk for lymphoma in particular. To date, the number of children exposed to biologicals is small. In addition, knowledge about the background incidence of malignancies in children with JIA and the influence of co-medication is limited.

Results

Between 2001 and 2009 five cases of malignancy were documented in the German JIA Etanercept in Children Registry covering 1200 patients, including one case each of non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, thyroid cancer, yolk sac cancer, and cervical dysplasia. All five patients had been treated with a number of other drugs including cytotoxic drugs (methotrexate, leflunomide, azathioprine, cyclosporine A) before institution of etanercept therapy. All patients were treated with etanercept, while two patients were also treated with adalimumab or infliximab. Malignancy appeared after an etanercept treatment period of between 3 weeks and more than 6 years. At the time of diagnosis, three patients were still on etanercept, five on methotrexate and one on infliximab. In three patients malignancy first occurred in adulthood. All patients recovered.

Conclusion

This case series of JIA and malignancy shows that prior to starting treatment with TNF-inhibitors careful consideration needs to be given to the possible benefits and risks. Patients need to be observed long-term and observation should to be continued in adulthood. Although a temporal association has been described to date, a causal role of TNF inhibitors cannot be excluded and parents and/or patients should be appropriately informed about this risk.

Keywords

Etanercept Adalimumab Infliximab Juvenile idiopathic arthritis Malignancy 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Asklepios Kinderklinik St. Augustin GmbHSt. AugustinDeutschland

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