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Erschienen in: rheuma plus 6/2020

07.08.2020 | Rheumatologie | tsDMARDs

Januskinase-Inhibitoren

State of the Art im klinischen Einsatz und Zukunftsperspektiven

verfasst von: Prof. Dr. R. Alten, M. Mischkewitz, A.-L. Stefanski, T. Dörner

Erschienen in: rheuma plus | Ausgabe 6/2020

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Zusammenfassung

Hintergrund

In der Pathogenese von Autoimmunerkrankungen spielen Zytokine und deren intrazelluläre Signalkaskaden eine zentrale Rolle. An dieser intrazellulären Signalübertragung sind auch sog. Januskinasen (JAK) beteiligt. Die zur Gruppe der „targeted synthetic disease-modifying antirheumatic drugs“ (tsDMARDs) zählenden Januskinase-Inhibitoren (JAKi) sind eine relativ junge und vielversprechende Wirkstoffklasse in der Therapie autoimmuner Krankheitsbilder.

Wirksamkeit

Mittlerweile sind für die Behandlung der rheumatoiden Arthritis (RA) drei Wirkstoffe, Tofacitinib, Baricitinib und Upadacitinib, in den USA, der Schweiz und der EU zugelassen. Auch Filgotinib, ein weiterer JAKi, zeigt vielversprechende Ergebnisse in der Therapie der RA. Darüber hinaus wurde Tofacitinib auch für die Therapie der ulzerativen Kolitis und der Psoriasisarthritis zugelassen. Zusätzlich zu den bereits genannten wurden und werden weitere JAKi wie Filgotinib oder Peficitinib in zahlreichen Studien zu Indikationen wie atopische Dermatitis, ankylosierende Spondylitis oder systemischer Lupus erythematodes untersucht.

Sicherheit

Als Immunsuppressiva weisen JAKi eine mit Biologika vergleichbare erhöhte Inzidenz für schwere Infekte auf. Bemerkenswert ist die erhöhte Reaktivierung des Varicella-Zoster-Virus. Auch Zytopenien treten unter JAKi-Therapie überhäufig auf. Klinisch relevant ist hierbei v. a. die beobachtete Lymphopenie, die mit einem erhöhten Auftreten von schweren Infekten assoziiert ist. Ein erhöhtes Risiko besteht weiterhin für thromboembolische Ereignisse, insbesondere Lungenembolien. Die Risiken hinsichtlich metabolischer Veränderungen und des Auftretens maligner Neoplasien sind vergleichbar mit denen unter Biologikatherapie.
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Metadaten
Titel
Januskinase-Inhibitoren
State of the Art im klinischen Einsatz und Zukunftsperspektiven
verfasst von
Prof. Dr. R. Alten
M. Mischkewitz
A.-L. Stefanski
T. Dörner
Publikationsdatum
07.08.2020
Verlag
Springer Vienna
Schlagwort
Rheumatologie
Erschienen in
rheuma plus / Ausgabe 6/2020
Print ISSN: 1868-260X
Elektronische ISSN: 2191-2610
DOI
https://doi.org/10.1007/s12688-020-00364-0

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