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Cladribin-Tabletten

Orale Immuntherapie der schubförmigen Multiplen Sklerose mit kurzen, jährlichen Behandlungsphasen

Cladribine tablets

Oral immunotherapy of relapsing-remitting multiple sclerosis with short yearly treatment periods

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Zusammenfassung

Hintergrund

Die selektive Modulation der Zahl und Funktion von Lymphozyten ist ein attraktives Konzept in der Therapie der schubförmigen MS (RMS).

Fragestellung

Seit August 2017 steht mit Cladribin-Tabletten (Mavenclad®) ein orales RMS-Medikament mit innovativem Behandlungskonzept zur Verfügung. Diese Übersicht fasst die aktuelle Datenlage und anwendungsorientierte Aspekte zusammen.

Ergebnisse

Cladribin-Tabletten werden in zwei Behandlungsphasen von jeweils 8 bis 10 (2-mal 4 bis 5) Tagen im Abstand von einem Jahr verabreicht und vermindern relativ gezielt die Anzahl von T‑ und B‑Lymphozyten, die sich in der Folge mit unterschiedlicher Kinetik allmählich rekonstituieren. Die ausgeprägte und langanhaltende Wirkung auf die klinische und paraklinische Krankheitsaktivität geht mit guter Verträglichkeit und einem insgesamt günstigen Sicherheitsprofil einher. Es besteht bei einem Teil der Patienten nach dem Absolvieren der zwei Behandlungsphasen die Aussicht auf eine längere therapiefreie Zeit ohne relevante Krankheitsaktivität. Regelmäßiges Monitoring der Lymphozytenzahlen und eine zuverlässige Kontrazeption in den vorgesehenen Zeitfenstern sind die wichtigsten Sicherheitsmaßnahmen. Es besteht kein Hinweis auf ein erhöhtes Malignomrisiko.

Schlussfolgerungen

Cladribin-Tabletten sind eine wichtige Erweiterung der Therapielandschaft bei RMS. Bei patientenfreundlichen kurzzeitigen Einnahmephasen und günstigem Nebenwirkungsprofil erreicht die Therapie eine länger anhaltende starke Reduktion der Krankheitsaktivität. Die primäre Zielgruppe für Cladribin-Tabletten sind Patienten mit relevanter Krankheitsaktivität (hochaktiver RMS) unter einer Erstlinientherapie z. B. mit injizierbaren Substanzen.

Abstract

Background

The selective modulation of lymphocyte numbers and function is an attractive concept in the treatment of relapsing-remitting multiple sclerosis (RMS).

Objective

Cladribine tablets (Mavenclad®), an oral RMS medication with an innovative treatment concept, have been available since August 2017. This review article summarizes the currently available clinical study data on cladribine tablets and aspects of their use in clinical practice.

Results

Cladribine tablets are administered during two treatment phases of 8–10 (two times 4–5) days with a 1-year interval. The drug selectively reduces the number of T and B lymphocytes, which are subsequently gradually reconstituted with divergent kinetics. A pronounced and sustained effect on the clinical and paraclinical MS disease activity is achieved with good tolerability and a favorable overall safety profile. After completing the two short treatment phases, a relevant proportion of the treated patients experience a prolonged treatment-free period with absence of relevant disease activity. Regular monitoring of lymphocyte counts and reliable contraception during the required time frames are the most important safety measures. There is no evidence of an increased risk of malignancies.

Conclusion

Cladribine tablets are an important addition to the therapeutic landscape in RMS. With patient-friendly short dosing periods and a favorable adverse event profile, cladribine tablets provide a sustained and strong reduction of MS disease activity. The primary target population for cladribine tablets is patients with relevant MS disease activity (highly active RMS) while on first-line treatment, e. g. with injectable disease-modifying drugs.

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Danksagung

Wir danken Dr. M. Fischer und Dr. P. Göttle für Hilfe bei Literatursuche und -analyse und Erstellung der Grafiken. Herr Dr. M. Fischer erhielt einen „unrestricted medical writing grant“ der Fa. Merck KG Darmstadt. Diese hatte keinen Einfluss auf den Inhalt des Manuskripts.

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Authors and Affiliations

  1. Klinik für Neurologie mit Institut für Translationale Neurologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A1, Westturm, Ebene 05, 48149, Münster, Deutschland

    S. G. Meuth & T. Ruck

  2. Klinik für Neurologie, Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, Düsseldorf, Deutschland

    O. Aktas & H.-P. Hartung

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  1. S. G. Meuth
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  3. O. Aktas
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  4. H.-P. Hartung
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Correspondence to S. G. Meuth.

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Interessenkonflikt

S.G. Meuth erhielt Vortragshonorare, Reisekostenerstattungen für Kongressteilnahmen und finanzielle Forschungsunterstützung von Almirall, Bayer Health Care, Biogen, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS und Teva. T. Ruck erhielt Reisekostenerstattungen von Merck Serono, finanzielle Forschungsunterstützung von Sanofi Genzyme und Novartis sowie Vortragshonorare von Sanofi Genzyme, Roche, Biogen, Merck und Teva. O. Aktas erhielt mit Genehmigung der Rektorin der Heinrich-Heine-Universität Honorare und Unterstützung für Beratung, Vorträge und wissenschaftliche Beiratstätigkeit von Almirall, Bayer, Biogen, Chugai, Medimmune, Novartis, Roche, Sanofi Genzyme und Teva. Diese Firmen erstatteten auch Reisekosten für Treffen dieser Beiräte. H.-P. Hartung erhielt mit Genehmigung der Rektorin der Heinrich-Heine-Universität Honorare für Beratung, Mitgliedschaft in Steering Committees und Data Monitoring Committees von Bayer, Biogen, Geneuro, Merck, Novartis, Receptos Celgene, Roche, Sanofi Genzyme und Teva. Diese Firmen erstatteten auch Reisekosten für Treffen dieser Committees.

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Meuth, S.G., Ruck, T., Aktas, O. et al. Cladribin-Tabletten. Nervenarzt 89, 895–907 (2018). https://doi.org/10.1007/s00115-018-0498-0

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