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Cladribin

Entwicklung einer oralen Formulierung zur Behandlung der Multiplen Sklerose

Cladribin

Development of an oral formulation for the treatment of multiple sclerosis

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Zusammenfassung

Bei der Multiplen Sklerose (MS) handelt es sich um eine chronische immunvermittelte Erkrankung des Zentralnervensystems, bei der autoreaktive CD4+- und CD8+-T-Lymphozyten, B-Lymphozyten, Makrophagen, Antikörper und Zytokine Markscheiden angreifen und Axone schädigen. Die gegenwärtig zur Verfügung stehenden Basistherapeutika bzw. krankheitsmodifizierenden Medikamente für MS erfordern regelmäßige und häufige parenterale Gaben; die Langzeit-Compliance ist dementsprechend unbefriedigend. Von allen derzeit in der Entwicklung befindlichen neuen, oralen MS-Mitteln ist Cladribin die einzige Substanz, bei der eine nur kurzzeitige Gabe mit langen therapiefreien Intervallen möglich erscheint. Cladribin ist ein Immunmodulator mit lang anhaltender Wirkung und einem auf der Grundlage einer über 15-jährigen Anwendungserfahrung mit der parenteralen Darreichungsform bei MS und anderen Indikationen gut charakterisierten Sicherheitsprofil. Neben dem Bedarf an neuen MS-Therapien zur Verbesserung der Compliance werden in der vorliegenden Arbeit auch der Wirkmechanismus von Cladribin, die zur Wirksamkeit und Sicherheit verfügbaren Daten sowie die klinische Entwicklung der oralen Cladribin-Formulierung beschrieben. Die jüngst veröffentlichten Ergebnisse der 96-wöchigen, doppelblinden, randomisierten, placebokontrollierten Multicenterstudie CLARITY (CLAdRIbine Tablets Treating MS OrallY) sind vielversprechend. Diese Studie belegt die Wirksamkeit von oralem Cladribin: Das Medikament reduziert die Schubrate, die Behinderungsprogression und die MR-Parameter der Krankheitsaktivität und -last.

Summary

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system in which autoreactive CD4+ and CD8+ T lymphocytes, B lymphocytes, macrophages, antibodies, and cytokines attack the myelin sheaths and damage the axons. The basic therapeutic agents and disease-modifying drugs that are currently available for MS require regular and frequent parenteral administration and therefore long-term compliance is unsatisfactory. Among all of the new oral MS agents presently under development, cladribine is the only substance that appears able to achieve long treatment-free intervals after only short-term administration. Cladribine is an immunomodulator with a long-lasting effect and a well-characterized safety profile based on over 15 years of experience with the parenteral route for MS and other indications. This contribution addresses the need for novel MS treatment approaches to improve compliance and describes the mechanism of action of cladribine, the available data on effectivity and safety, and the clinical development of the oral formulation of cladribine. The results from the recently published 96-week, double-blind, randomized, placebo-controlled, multicenter study CLARITY (CLAdRIbine Tablets Treating MS OrallY) are very promising. They clearly show that oral cladribine reduces relapse rate, disability progression and disease activity and burden as evidenced by MRI.

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Danksagung

Die Autoren danken Dr. Nobert Zessack, MerckSerono, für die kritische Durchsicht, Dr. Patrick Küry, Düsseldorf, für die Hilfe bei den Abbildungen und Dr. Andrea Plant, Caudex Medical, für die technische Hilfe bei der Abfassung des Manuskripts.

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Der korrespondierende Autor erklärt, mit Genehmigung des Rektors der HHU Honorare für Beratung, Vorträge und Tätigkeit in Steering Committees von folgenden Firmen erhalten zu haben: BayerSchering, BiogenIdec, BioMS, Genzyme, MerckSerono, Novartis, Teva, Sanofi Aventis.

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  1. Neurologische Klinik, Heinrich-Heine-Universität, Moorenstraße 5, 40225, Düsseldorf, Deutschland

    H.-P. Hartung, B.C. Kieseier & O. Aktas

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  1. H.-P. Hartung
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  2. B.C. Kieseier
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  3. O. Aktas
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Correspondence to H.-P. Hartung.

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Hartung, HP., Kieseier, B. & Aktas, O. Cladribin. Nervenarzt 81, 194–202 (2010). https://doi.org/10.1007/s00115-009-2878-y

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