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Selektive Kostimulationsblockade

CTLA4-Ig (Abatacept)

Selective co-stimulation blockade

CTLA4-Ig (Abatacept)

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Zusammenfassung

Abatacept ist ein lösliches Fusionsprotein, bestehend aus der extrazellulären Domäne des humanen CTLA4-Moleküls, welches an die modifizierte Fc-Region des humanen IgG1 gebunden ist. Es ist zur Behandlung der rheumatoiden Arthritis (RA) in Kombination mit Methotrexat und der juvenilen chronischen Arthritis zugelassen und wirkt über eine Blockade des kostimulatorischen Signals, welches für eine vollständige T-Zell-Aktivierung benötigt wird. Abatacept hat das Spektrum der zielgerichteten Biologika-Therapien der RA erweitert und ist insbesondere auch bei RA-Patienten mit Anti-TNF-α-Therapie-Versagen wirksam. Das umfangreiche Studienprogramm hat Daten zum Einsatz nach TNF-Versagen, aber auch nach DMARD-Versagen vorgelegt. Es wird entsprechend seiner Zulassung bisher bei RA-Patienten nach Versagen oder UAW von TNF-α-Inhibitoren eingesetzt. Die EMEA hat jüngst eine Zulassungserweiterung nach DMARD-Versagen genehmigt. Ein ähnlich gutes Ansprechen von Abatacept bei RA nach DMARD- wie nach Anti-TNF-Versagen impliziert unterschiedliche Angriffspunkte von Abatacept und Anti-TNF und lässt die Frage aufkommen, welche Patienten frühzeitig von dem einen oder dem anderen Therapieprinzip besser profitieren. In Bezug auf das Sicherheitsprofil wurde bisher keine Häufung von Malignomen über die bei RA-Patienten bekannte Tumorinzidenz hinaus beobachtet, wobei Langzeitdaten über mehr als 10 Jahre noch nicht vorliegen. Opportunistische Infektionen scheinen nicht gehäuft aufzutreten.

Abstract

Abatacept is a soluble fusion protein comprising the extracellular domain of human CTLA4 linked to the modified Fc portion of human IgG1. It is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate and juvenile chronic arthritis by blocking the co-stimulatory signal required for full T-cell activation. Abatacept has added to the growing armamentarium of targeted therapies for RA, including the challenging group of RA patients who are refractory to TNF-α blockade. To date, abatacept has its main application in cases failing to respond to TNF-α blockade. In several studies, the efficacy and safety of abatacept was not only shown for TNF-IR patients, but also for DMARD-IR patients. Recently, the EU has approved abatacept in combination with methotrexate in DMARD-IR patients. The significant and similar response rates in TNF-α blockade failure to those observed in only DMARD failure implies that the pathways targeted with the two treatments remain distinct. In terms of safety profile, incidence rates of malignancy in the abatacept trials were consistent with those in a comparable RA population. The rate of opportunistic infections does not seem to be increased in patients treated with abatacept.

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Interessenkonflikt

Die korrespondierende Autorin weist auf folgende Beziehungen hin: E. Märker-Hermann hat Honorare für Referententätigkeiten (Firma BMS) erhalten.

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  1. Klinik Innere Medizin II, Rheumatologie, klinische Immunologie und Osteologie, Schlosspark-Klinik, Akademisches Lehrkrankenhaus, Charité-Universitätsmedizin Berlin, Heubnerweg 2, 14059, Berlin, Deutschland

    R. Alten

  2. Klinik Innere Medizin IV (Rheumatologie, klinische Immunologie und Nephrologie) der, HSK Dr. Horst Schmidt Klinik GmbH, Wiesbaden, Deutschland

    E. Märker-Hermann

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  1. R. Alten
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Alten, R., Märker-Hermann, E. Selektive Kostimulationsblockade. Z. Rheumatol. 69, 601–607 (2010). https://doi.org/10.1007/s00393-009-0533-4

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  • DOI: https://doi.org/10.1007/s00393-009-0533-4

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