Therapie der Multiplen Sklerose mit monoklonalen Antikörpern: aktualisierte Empfehlungen zum Umgang mit Natalizumab im Rahmen eines Expertenmeetings

Zusammenfassung

Die Behandlung der Multiplen Sklerose (MS) wird zunehmend durch innovative Antikörpertherapien erweitert. Neben dem 2006 zugelassenen Natalizumab für den Einsatz bei der hochaktiven, schubförmigen MS werden bereits jetzt im Rahmen von Studien bzw. im Off-label-Ansatz zahlreiche weitere monoklonale Antikörper bei MS-Patienten verwendet, die häufig eine über die übliche immunmodulatorische Therapie hinausreichende Wirksamkeit zeigen. Neben neuen therapeutischen Chancen stellen sich allerdings zunehmend die Risiken dieser Therapien heraus. Als prototypisches Beispiel dient Natalizumab, bei dem die höhere klinische Effektivität mit zwar seltenen, allerdings teilweise schwerwiegenden Nebenwirkungen wie anaphylaktischen Reaktionen oder einer progressiven multifokalen Leukenzephalopathie (PML) einhergeht. Die folgende Übersicht stellt daher den aktuellen Stand von Empfehlungen dar, welche als Resultate eines Expertentreffens im März des Jahres 2010 zusammengestellt sind. Ziel des Treffens war die kritische Diskussion und die Entwicklung von praktischen Anleitungen für den Einsatz von monoklonalen Antikörpern im klinischen Einsatz, speziell Natalizumab. Berücksichtigt sind hierbei auch die Empfehlungen der Europäischen Zulassungsbehörde (European Medicines Agency, EMA) vom 21.1.2010, die eine Aktualisierung der Natalizumab-Arztinformation beinhalten und der aktuellen Einschätzung von Nutzen und Risiko Rechnung tragen. Die aktualisierten Hinweise sollen die Rahmenbedingungen für Indikation, die logistischen Voraussetzungen dieser Therapie, die Therapieüberwachung sowie Diagnostik- und Behandlungsalgorithmen bei Komplikationen definieren. Damit soll ein Beitrag zum praktischen Umgang mit Komplikationen in der Behandlungsrealität geleistet werden. Prinzipiell sollen durch den vernetzten Informationsfluss auf der Basis kooperativer Strukturen wie Versorgungsnetzwerken die Erkennung und Behandlung von Komplikationen verbessert und damit der Einsatz innovativer und teils risikoreicherer monoklonaler Antikörpertherapien erleichtert werden.

Abstract

During recent years a series of novel and powerful monoclonal antibody therapies for the treatment of multiple sclerosis (MS) have been introduced and studied. In the vanguard of these therapies, natalizumab was initially licensed for highly active relapsing MS four years ago. Other monoclonal antibodies are either currently being used as off-label treatments or are being actively studied in clinical trials. The association of monoclonal antibody therapy, e. g., natalizumab, with rare but potentially fatal events such as JC virus-mediated progressive multifocal encephalopathy (PML) represents a major challenge. This report compiles the results of an expert meeting held in March 2010. In consideration of the recent recommendations of the European Medicines Agency (EMA), the following meeting report aims to provide updated suggestions for therapy with natalizumab in daily clinical routine. The aim is to provide a framework for the use of these novel and future immunotherapies in routine clinical practice and to improve the handling of potential complications of these treatments in both inpatient and outpatient settings. The proposed algorithms strongly depend on the structured and ongoing interaction between different levels of health-care providers in order to establish robust quality standards for ensuring patient safety and maintaining a favourable risk-benefit ratio.

Multiple Sklerose - Immuntherapie - monoklonale Antikörper - Natalizumab - PML

multiple sclerosis - immunotherapy - monoclonal antibodies - natalizumab - PML

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1 Mitglieder der Expertengruppe:

1 Ortwin Adams, Düsseldorf; Orhan Aktas, Düsseldorf; Gabriele Arendt, Düsseldorf; Karl Baum, Henningsdorf; Antonios Bayas, Augsburg; Joseph Berger, Lexington, Kentucky, USA; Andreas Bitsch, Neuruppin; Mathias Buttmann, Würzburg; Andrew Chan, Bochum; Tobias Derfuß, Erlangen / Basel; Ralf Gold, Bochum; Klaus Gottwald, Stuttgart; Judith Haas, Berlin; Lutz Harms, Berlin; Hans-Peter Hartung, Düsseldorf; Holger Honig, Bremerhaven; Boris Kallmann, Bamberg; Zaza Katsarava, Essen; Bernd Kieseier, Düsseldorf; Christoph Klawe, Trier; Ingo Kleiter, Regensburg; Tania Kümpfel, München; Michael Lang, Ulm; Volker Limmroth, Köln; Ralf Linker, Bochum / Erlangen; Martin Marziniak, Münster; Erich Mauch, Dietenbronn; Matthias Mäurer, Bad Mergentheim; Uwe Meier, Grevenbroich; Ernst-Wilhelm Radü, Basel, Schweiz; Thorsten Rosenkranz, Hamburg; Stephan Schmidt, Bonn; Thorsten Schultheiss, Dresden; Kurt-Wolfram Sühs, Homburg; Martin Stangel, Hannover; Florian Stögbauer, Osnabrück; Björn Tackenberg, Marburg; Florian Then Bergh, Leipzig; Hayrettin Tumani, Ulm; Heinz Wiendl, Münster; Brigitte Wildemann, Heidelberg; Ulf Ziemann, Frankfurt.