Zusammenfassung
In Deutschland wurden die ersten JAK(Januskinase)-Inhibitoren 2017 für die Therapie der rheumatoiden Arthritis zugelassen. Ihr Wirkmechanismus beruht, anders als der der Biologika, auf einer Hemmung vieler Zytokine. Sie haben gegenüber den Biologika den Vorteil der oralen Applikation, 3 der 4 jetzt zugelassenen JAK-Inhibitoren waren in Vergleichsstudien gegenüber Adalimumab zumindest bei einigen Wirksamkeitsendpunkten überlegen, sie sind wegen einer kurzen Halbwertszeit gut steuerbar und haben eine besonders gute Wirksamkeit auf den Schmerz. Andererseits war die Rate an Malignomen und kardiovaskulären Ereignissen im Vergleich von Tofacitinib und TNF(Tumornekrosefaktor)-Inhibitoren in der Oral Surveillance-Studie, aber nicht in den Zulassungsstudien und im CorEvitas-Register erhöht. Die Klärung dieser Sicherheitsdiskussion und die Auswertung von Registerdaten wird entscheiden, wo die JAK-Inhibitoren künftig im Therapiealgorithmus der rheumatoiden Arthritis positioniert werden.
Abstract
In 2017 the first Janus kinase (JAK) inhibitors were approved for the treatment of rheumatoid arthritis in Germany. The mode of action of JAK inhibitors differs from biologicals, as multiple cytokines are inhibited. In comparison with the treatment with biologicals, JAK inhibitors have the advantage of oral application, three of the four currently approved JAK inhibitors were superior to adalimumab in at least some of the endpoints in randomized controlled trials, they have a short half-life and have a particular efficacy in the control of pain. On the other hand, the rate of malignancies and major cardiovascular events was increased in the Oral Surveillance trial in comparison with tofacitinib and tumor necrosis factor (TNF) inhibitors but not in the CorEvitas registry and not in the phase III approval trials. The clarification of these safety discussions and the evaluation of further registry data will decide the position of JAK inhibitors in the therapeutic algorithm for rheumatoid arthritis.
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T. Witte hat Honorare für Vorträge von den Firmen Pfizer, AbbVie, Lilly und Galapagos erhalten.
Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.
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Katinka Albrecht, Berlin
Klaus Krüger, München
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Witte, T. Januskinaseinhibitoren. Z Rheumatol 81, 94–99 (2022). https://doi.org/10.1007/s00393-021-01125-w
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DOI: https://doi.org/10.1007/s00393-021-01125-w