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Arthritis und Rheuma 2014; 34(05): 308-313
DOI: 10.1055/s-0037-1619113
Kinderrheumatologie: Übersichtsarbeit
Schattauer GmbH

Pharmakogenetik bei juveniler idiopathischer Arthritis

Pharmacogenetics in juvenile idiopathic arthritis
H. Schmeling
1   Section of Rheumatology, Department of Paediatrics, Alberta Children’s Hospital, University of Calgary, Calgary/AB, Canada
2   Alberta Children’s Hospital Research Institute for Maternal and Child Health, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary/AB, Canada
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Publication History

Publication Date:
27 December 2017 (online)

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Zusammenfassung

Die juvenile idiopathische Arthritis (JIA) ist die häufigste chronische rheumatische Erkrankung im Kindesalter. Viele Kinder benötigen nach Diagnosestellung über viele Jahre immunmodulierende Therapien. Ein beträchtlicher Anteil von Kindern zeigt schwere therapierefraktäre Verläufe und einige entwickeln schwerwiegende Medikamentennebenwirkungen. Zahlreiche Genpolymorphismen wurden als potenzielle prädiktive Biomarker in klinischen Studien zur Pharmako genetik von Methotrexat und Etanercept bei der JIA analysiert, ohne jedoch eindeutige Ergebnisse erbracht zu haben. Dies ist möglicherweise auf kleine und klinisch heterogene Studienpopulationen, Unterschiede in der Bewertung der Krankheitsaktivität und der Analyse von nur wenigen Kandidatengenvarianten zurückzuführen. Die erste pharmakogenetische genomweite Untersuchung bei der JIA hat Genregionen von besonderem biologischen Interesse identifiziert. Eine Validierung ist jedoch erforderlich. Die Entdeckung neuer pharmakogenetischer Biomarker und deren Netzwerke können zur Entwicklung neuer Medikamente führen und eine „individuelle“ Therapie ermöglichen, die das Nutzen-Risiko-Verhältnis einer Therapie für den einzelnen JIA-Patienten verbessert.

Summary

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. Many children require immunomodulatory therapies for many years following diagnosis. A considerable proportion of children experience therapeutic inefficacy or substantial adverse effects. The identification of valid candidate gene variants in many clinical pharmacogenetic studies of Methotrexate and Etanercept in JIA has seen little success to date. This is possibly due to heterogenic small study populations, differences in disease activity outcome parameters that have been used and the small number of candidate gene variants analysed. The first genome-wide pharmacogenetic study in JIA has identified gene regions of particular biological interest, but these findings require validation. The discovery of new pharmacogenomic biomarkers and systems pathways can provide new drug targets and will enable individualized drug therapy with improving the risk-benefit ratios of immunomodulatory therapies in JIA.

Schlüsselwörter

Juvenile idiopathische Arthritis - Pharmakogenetik - Methotrexat - Etanercept

Keywords

Juvenile idiopathic arthritis - pharmakogenetics - methotrexate - etanercept
 

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