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Zelldepletion und Myeloablation bei neuroimmunologischen Erkrankungen

Cell depletion and myoablation for neuroimmunological diseases

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Zusammenfassung

Hintergrund

Die Therapie autoimmuner Erkrankungen des Nervensystems fußt auf Eingriffen in die zugrunde liegenden Immunprozesse.

Ziel der Studie

Eine Zusammenfassung der zur Verfügung stehenden zelldepletierenden und myeloablativen Konzepte bei neuroimmunologischen Erkrankungen.

Methoden

Auswertung der Studienlage bezüglich der Multiplen Sklerose (MS) als bestuntersuchter neuroimmunologischer Entität.

Ergebnisse

Es stehen drei Konzepte zur Verfügung: Klassische Immunsuppressiva wie Azathioprin, Mitoxantron und Cyclophosphamid erreichen durch eine generelle Leukopenie moderate Effekte auf die Krankheitsaktivität. Die Myeloablation mit anschließender autologer Stammzelltransplantation ist eine hochwirksame Behandlung mit oft langanhaltendem Effekt. Sie ist verbunden mit schwerwiegenden, teils lebensgefährlichen Nebenwirkungen. Selektive Antikörper gegen Lymphozytensubpopulationen wie Alemtuzumab (Anti-CD52), Rituximab und Ocrelizumab (beide Anti-CD20) zeigen eine hohe Wirksamkeit auf die entzündliche Krankheitsaktivität bei der schubförmigen MS. Für Ocrelizumab konnte außerdem ein Effekt bei der primär progredienten MS gezeigt werden.

Diskussion

Die präsentierten zelldepletierenden oder myeloablativen Therapien sind zumeist hochwirksam, aber mit signifikanten Risiken verbunden. Ihr Einsatz sollte daher im Vergleich mit den zahlreicher werdenden alternativen Methoden der Immunmodulation sorgsam abgewogen werden.

Abstract

Background

The treatment of autoimmune disorders of the nervous system is based on interventions for the underlying immune phenomena.

Objective

To summarize concepts of cell depletion and myeloablation studied in the context of neuroimmunological disorders.

Method

Evaluation of the available literature on multiple sclerosis as the most widely studied neuroimmunological entity.

Results

Three concepts have been introduced: classical immunosuppressants, such as azathioprine, mitoxantrone and cyclophosphamide exert general lymphopenic effects and thereby moderately decrease disease activity. Myeloablative regimens combined with autologous hematopoietic stem cell transplantation have a profound and in most cases long-lasting impact on autoimmunity at the cost of potentially life-threatening side effects. Alemtuzumab (anti-CD52), rituximab and ocrelizumab (both anti-CD20) are depleting antibodies directed against certain lymphocyte subsets and substantially ameliorate disease activity in relapsing-remitting multiple sclerosis. Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.

Conclusions

Most of the presented cell-depleting and myeloablative therapies are highly effective treatment options but are also accompanied by significant risks. In the context of the increasing number of alternative immunomodulatory options the indications for use should be cautiously considered.

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Authors and Affiliations

  1. Neurologische Klinik und Poliklinik, Universitätsspital Basel, Petersgraben 4, 4031, Basel, Schweiz

    M. Diebold, L. Kappos &  T. Derfuss

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  1. M. Diebold
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  2. L. Kappos
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  3. T. Derfuss
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Corresponding author

Correspondence to T. Derfuss.

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Interessenkonflikt

Das Universitätsspital Basel hat in den vergangenen 3 Jahren folgende Unterstützungen erhalten, die ausschließlich für Forschungszwecke eingesetzt wurden: Entgelte für Steering Committees, Advisory Boards und Beratungen von Actelion, Alkermes, Almirall, Bayer, Biogen, Excemed, GeNeuro SA, Genzyme, Merck, Mitsubishi Pharma, Novartis, Receptos, Roche, Sanofi-Aventis, Santhera, Teva, Vianex and royalties from Neurostatus Systems AG. Es wurden außerdem Honorare für Fortbildungsveranstaltungen von Allergan, Almirall, Bayer, Biogen, Excemed, Genzyme, Merck, Novartis, Pfizer, Sanofi-Aventis, Teva and UCB angenommen. Die Institution hat zusätzlich in den letzten 24 Monaten Subventionen für Patientendienste von Bayer, Merck und Teva erhalten. T. Derfuss fungierte in den letzten 24 Monaten als Principal Investigator der folgenden Medikamentenstudien ACROSS (Fingolimod, Novartis), GeNeuro, EXPAND (Siponimod, Novartis), MOMENTUM (Amiselimod, Mitsubishi) und OPERA (Ocrelizumab, Roche). L. Kappos fungierte in den letzten 24 Monaten als Principal Investigator der folgenden Medikamentenstudien BOLD EXT., EXPAND (BAF312, Novartis), DECIDE, DECIDE EXT. (Daclizumab HYP, Biogen), ENDORSE (BG00012, Biogen), FINGORETT, FTY-UMBRELLA, INFORMS, INFORMS EXT LONGTERM. (Fingolimod, Novartis), MOMENTUM (Amiselimod, Mitsubishi) OCRELIZUMAB PHASE II EXT., OPERA, ORATORIO (Ocrelizumab, Roche), REFLEXION (IFN β‑1a, Merck), STRATA EXT. (Natalizumab, Biogen Idec) and TERIFLUNOMIDE EXT. (Teriflunomide, Sanofi-Aventis). M. Diebold erklärt keine potenziellen persönlichen Interessenkonflikte. Die Forschung des MS-Zentrums in Basel wurde durch Bayer, Biogen, Novartis, die Schweizerische MS Gesellschaft, den Schweizerischen Nationalfonds für die Förderung der Wissenschaft, die Europäische Union und die Roche Research Foundation unterstützt.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Diebold, M., Kappos, L. & Derfuss, T. Zelldepletion und Myeloablation bei neuroimmunologischen Erkrankungen. Nervenarzt 87, 814–820 (2016). https://doi.org/10.1007/s00115-016-0156-3

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