Infektiöse Komplikationen als Folge der Behandlung mit Nukleosidanaloga und monoklonalen Antikörpern

Zusammenfassung

Monoklonale Antikörper gegen CD 20 (Rituximab), CD 52 (Alemtuzumab), CD 25 (Basiliximab), und Tumornekrosefaktor-alfa (Infliximab, Etanercept, Adalimumab) werden bei einem breiten Spektrum von Erkrankungen eingesetzt. Sie haben zu einer deutlichen Verbesserung der Therapiemöglichkeiten etwa bei malignen lymphatischen Neoplasien, bei der Transplantatabstoßung, bei rheumatoider Arthritis und bei chronisch-entzündlichen Darmerkrankungen geführt. Ihr Einsatz ist jedoch mit einer profunden und teils lang anhaltenden Immunsuppression verbunden, die je nach individueller Risikokonstellation zu schweren Infektionen führen kann. Septische bakterielle Infektionen, invasive Mykosen, Zytomegalievirusinfektionen (CMV) sowie Tuberkulosen können insbesondere unter Alemtuzumab und TNF-Antikörpertherapie auftreten. Nukleosidanaloga wie Fludarabin und Cladribin sind wegen ihrer lang anhaltenden T-Zell-Suppression mit einem erhöhten Risiko opportunistischer Infektionen, insbesondere durch CMV oder Pneumocystis jiroveci, assoziiert. Bei intensiv immunsuppressiv vorbehandelten Patienten steigt dieses Risiko deutlich an. Dies gilt ganz besonders für Patienten mit malignen Lymphomen, die mit einer Kombination (bzw. Sequenz) von Nukleosidanaloga und Alemtuzumab behandelt werden. Die prophylaktische Gabe antiviraler Substanzen gegen Herpesviren sowie von Cotrimoxazol ist bei Patienten unter Therapie mit Alemtuzumab oder Nukleosidanalgoa obligat.

Summary

Recombinant monoclonal antibodies targeted against cell surface antigens such as CD 20 (rituximab), CD 52 (alemtuzumab), CD 25 (basiliximab) or against tumor necrosis factor (TNF)-alpha (infliximab, etanercept, adalimumab) are in clinical use for a broad range of diseases, resulting in a significant improvement of treatment options for lymphoid malignancies, transplant rejection, rheumatoid arthritis and chronic inflammmatory bowel disease. However, their administration induces a profound and long lasting immunosuppression which may be associated with serious infections in selected patients. Invasive bacterial and fungal infections as well as systemic viral infections, preferably due to cytomegalovirus (CMV), and mycobacterial infections may emerge particularly in patients treated with alemtuzumab and TNF antibodies. Nucleoside analogs such as fludarabine or cladribine induce a severe T cell suppression putting patients at risk for opportunistic infections caused by CMV, Pneumocystis jiroveci and others. In patients heavily pretreated with immunosuppressive agents, this risk of infectious complications increases significantly. This is particularly important in patients with malignant lymphomas treated with a combination (or sequence) of nucleoside analogs and alemtuzumab. Prophylactic administration of antivirals against Herpes viruses as well as cotrimoxazole is mandatory in patients treated with alemtuzumab or nucleoside analogs.

Infektionen - Fludarabin - Cladribin - Rituximab - Alemtuzumab - Infliximab - Etanercept - Adalimumab - Basiliximab

Infections - Fludarabine - Cladribine - Rituximab - Alemtuzumab - Infliximab - Etanercept - Adalimumab - Basiliximab

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