Morbus Crohn - Infliximab, Adalimumab und Certolizumab-Pegol - Was bringen die neuen Gegenspieler des TNF-α?

Therapeutische Antikörper gegen TNF-α sind eine bedeutende Innovation in der Behandlung des komplizierten Morbus Crohn. Neben dem chimären Infliximab gibt es mit Adalimumab und Certolizumab-Pegol zwei weitere Antikörper. Die drei Antikörper zeigen einen schnellen Wirkeintritt, wobei zwei Drittel der Patienten mit refraktärem Morbus Crohn eine initiale Besserung zeigen und nur 20-30 % der Patienten langfristig in Remission gehalten werden können. Verschluss aktiver Fisteln und die Reduktion einer chronischen Glukokortikoidmedikation sind weitere wichtige Indikationen zur Anti-TNF-α-Therapie. Der Einsatz der Anti-TNF-α-Therapie sollte langfristig und als chronische Gabe über Jahre geplant werden. Die Antikörper erkennen unterschiedliche Epitope, haben aber ein überlappendes Wirkspektrum. Versagt einer, kann ein anderer (insbesondere bei Wirkungsverlust nach anfänglichem Therapieerfolg) durchaus noch Wirkung zeigen. Ein Einsatz der neueren Anti-TNF-α-Antikörper ohne Komedikation mit Azathiopin ist möglich. Schwere Nebenwirkungen, wie ein erhöhtes Infektions- und Krebsrisiko sind ein Klasseneffekt und eng mit dem Wirkmechanismus verbunden. Der Therapieerfolg überwiegt allerdings das Nebenwirkungsrisiko bei richtiger Auswahl der Patienten. Ein Tuberkulose-Screening muss vor jeder immunsuppressiven Therapie, insbesondere aber von einer Anti-TNF-α-Therapie erfolgen. Das Vorliegen eines Abszesses muss ausgeschlossen werden. Symptome eventueller infektiöser Komplikationen müssen Anlass zu einer frühen diagnostischen Abklärung sein. Patienten sollten im Rahmen von Registern dokumentiert werden. Leitlinien des Kompetenznetztes „Darmerkrankungen„ und der DGVS zur Behandlung der CED erläutern des Einsatz von Anti-TNF-α-Medikamenten im Detail.

Summary

Therapeutic antibodies against TNF-α are an important therapeutic innovation in recent years in treating complicated Crohn's disease. Chimeric infliximab fully human produced Adalimumab and Certolizumab-Pegol, a humanized, PEGylated anti-TNF-α antibody Fab fragment, are therapeutic antibodies against TNF. All three antibodies have a rapid onset of action, with two thirds of the patients with refractory Crohn's disease showing an initial clinical response to the anti-TNFa treatment and only 20-30 % develops a lasting remission. Clinical benefits include closure of draining fistulas and reduction of chronic glucocorticoid medication. When considering an anti TNF-α therapy a long term strategy is needed and a systematic maintenance treatment should be developed. The antibodies recognize different epitopes but have a complementary mode of action. Does one antibody fail, especially after an initial clinical response, a second antibody can still show an effect. More recent anti TNF-α antibodies can be applied without an azathioprine comedication. Severe side effects like an increase risk of infection and malignancies are a class effect and closely linked to the mode of action. When patients are properly selected, the clinical benefit outweighs the side effects. Before starting an immunosuppressive therapy or an anti-TNF-α therapy screening for latent tuberculosis is mandatory. An abscess has to be excluded. Due to the high risk of infection any symptoms which might be a sign of complications during therapy should result in a thorough diagnostic examination. Patients should be documentated in registries.

Key words

anti-TNF-α-treatment - induction and maintenance therapy - safety profile - therapeutic concepts

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