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Stellenwert der neuen Biologicals und Zytokinantagonisten in der Therapie der juvenilen idiopathischen Arthritis (JIA)

Treatment of juvenile idiopathic arthritis

  • BEITRAG ZUM SCHWERPUNKTTHEMA
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Zusammenfassung

Die JIA ist eine heterogene Gruppe von Erkrankungen mit den gemeinsamen Merkmalen einer chronischen Arthritis unklarer Ätiologie und Auftreten im Kindesalter. Im Vergleich zur rheumatoiden Arthritis sind Präsentation und Verlauf deutlich variabler. Dennoch bestehen Gemeinsamkeiten. Fortschritte im Verständnis der Entzündungsreaktion, in der Molekularbiologie und der Biotechnologie ermöglichen die Herstellung und Anwendung zahlreicher Biologika, die gezielt einzelne als bedeutsam erkannte immunologische Mechanismen blockieren. Zahlreiche Biologika wurden bereits in klinischen Studien an erwachsenen Patienten mit rheumatoider Arthritis, ankylosierender Spondylitis, Psoriasis oder Psoriasisarthritis geprüft und eine stetig steigende Zahl wurde zur Behandlung zugelassen.

Bisherige Therapieerfahrungen mit der Tumor-Nekrose-Faktor (TNF)-Blockade durch den löslichen Rezeptor Etanercept und durch die monoklonalen Antikörper Infliximab und Adalimumab zeigen eine bedeutende Effektivität auf klinische und labormedizinische Aktivitätsparameter auch im Kindes- und Jugendalter. Die Therapie der juvenilen idiopathischen Arthritis mit TNF-Antagonisten gilt heute unter bestimmten Bedingungen als indiziert und hat ihren festen Platz im Therapiealgorithmus gefunden. Bei der Methotrexat-refraktären Polyarthritis ist Etanercept als einzig zugelassenes Biologikum Medikament der ersten Wahl. Der Abschluss der klinischen Prüfung und die Zulassung von Adalimumab und Infliximab sind in Kürze zu erwarten. Insbesondere für Patienten mit einer begleitenden, konventionell therapeutisch nicht ausreichend beeinflussbaren und den Visus bedrohenden Uveitis ist heute schon der Einsatz von TNF-Antikörpern vertretbar. Auch bei der juvenilen ankylosierenden Spondylitis ist der Einsatz von TNF-Antagonisten bei entsprechender Krankheitslast indiziert.

Eine Therapie mit anderen Biologika, dem Interleukin-1-Rezeptorantagonisten Anakinra oder auch Atlizumab (MRA), einem Antikörper gegen IL-6 Rezeptoren oder Abatacept, einem inhibitorischen Liganden des co-stimulatorischen T-Zellmembranmoleküls CD28, gelten derzeit noch als experimentell und bleiben dem Einsatz im Rahmen von Studien vorbehalten. Bei der Anwendung von Biologika im Kindes- und Jugendalter sind die Empfehlung der Fachgesellschaften zu beachten.

Summary

Juvenile idiopathic arthritis is group of diseases of unknown aetiology characterised by the occurrence of chronic arthritis during childhood. Compared to adult onset rheumatoid arthritis, its course is more variable. Increasing knowledge of the inflammatory process as well as in molecular genetics and biotechnology has enable the production of new drugs, the biologicals. These are able to specifically block mechanisms of immune activation and thereby interfere with the inflammatory process. An increasing number of biologicals have been tried in clinical studies in adults suffering from rheumatoid arthritis, psoriasis or psoriasis arthritis and a couple of them were already licensed for treatment.

Treatment of juvenile idiopathic arthritis by blockade of tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the monoclonal antibodies Infliximab and Adalimumab showed comparable clinical efficacy. Blockade of TNF therefore already reached a certain place in the therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently, only Etanercept is licensed for treatment of active juvenile polyarthritis refractory to methotrexate. Studies using Infliximab and Adalimumab will be completed in the near future. However, antibodies blocking TNF may already be used in patients suffering from active uncontrolled chronic uveitis in whom visual impairment is threatening. TNF blockers may also be indicated in juvenile ankylosing spondylitis.

The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies.

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  1. Asklepios Klinik für Kinder- und Jugendmedizin Sankt-Augustin, 53757, Sankt Augustin

    G. Horneff

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Horneff, G. Stellenwert der neuen Biologicals und Zytokinantagonisten in der Therapie der juvenilen idiopathischen Arthritis (JIA). Z. Rheumatol. 64, 317–326 (2005). https://doi.org/10.1007/s00393-005-0748-y

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