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Ocrelizumab Treatment in Patients with Primary Progressive Multiple Sclerosis: Short-term Safety Results from a Compassionate Use Programme in Germany.
Rauer, Sebastian; Hoshi, Muna-Miriam; Pul, Refik; Wahl, Mathias; Schwab, Matthias; Haas, Judith; Ellrichmann, Gisa; Krumbholz, Markus; Tackenberg, Björn; Saum, Kai-Uwe; Buck, Fabian; Leemhuis, Jost; Kretschmann, Anita; Aktas, Orhan.
Afiliación
  • Rauer S; Klinik für Neurologie und Neurophysiologie, Universitätsklinikum Freiburg, Freiburg, Germany. Electronic address: sebastian.rauer@uniklinik-freiburg.de.
  • Hoshi MM; Neurologische Klinik, Technische Universität München, Munich, Germany. Electronic address: muna.hoshi@ms-klinik.de.
  • Pul R; Klinik für Neurologie, Universitätsklinikum Essen, Essen, Germany. Electronic address: refik.pul@uk-essen.de.
  • Wahl M; Zentrum der Neurologie und Neurochirugie, Universitätsklinikum Frankfurt, Frankfurt, Germany. Electronic address: wahl@med.uni-frankfurt.de.
  • Schwab M; Klinik für Neurologie, Universitätsklinikum Jena, Jena, Germany. Electronic address: matthias.schwab@med.uni-jena.de.
  • Haas J; Jüdisches Krankenhaus Berlin, Berlin, Germany. Electronic address: judith.haas@jkb-online.de.
  • Ellrichmann G; Klinik für Neurologie, St. Josef-Hospital, Bochum, Germany. Electronic address: gisa.ellrichmann@rub.de.
  • Krumbholz M; Department of Neurology & Stroke and Hertie-Institute for Clinical Brain Research, Eberhard Karl University of Tübingen, Tübingen, Germany. Electronic address: markus.krumbholz@uni-tuebingen.de.
  • Tackenberg B; Zentrum für Neuroimmunologie, Universitätsklinikum Marburg, Marburg, Germany; F. Hoffmann-La Roche AG, Basel, Switzerland. Electronic address: tackenbb@staff.uni-marburg.de.
  • Saum KU; Roche Pharma AG, Grenzach-Wyhlen, Germany. Electronic address: kai-uwe.saum@roche.com.
  • Buck F; Roche Pharma AG, Grenzach-Wyhlen, Germany. Electronic address: fabian.buck@roche.com.
  • Leemhuis J; Roche Pharma AG, Grenzach-Wyhlen, Germany. Electronic address: jost.leemhuis@roche.com.
  • Kretschmann A; Roche Pharma AG, Grenzach-Wyhlen, Germany. Electronic address: anita.kretschmann@roche.com.
  • Aktas O; Klinik für Neurologie, Medizinische Fakultät, Universitätsklinikum Düsseldorf, Düsseldorf, Germany. Electronic address: orhan.aktas@med.uni-duesseldorf.de.
Clin Neurol Neurosurg ; 197: 106142, 2020 10.
Article en En | MEDLINE | ID: mdl-32920498
ABSTRACT

OBJECTIVES:

In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a phase 3 randomised controlled trial. Eleven months prior to the European regulatory approval, a compassionate use programme (CUP) made ocrelizumab available to 489 patients with PPMS in Germany, thereby for the first time providing a therapeutic option to patients with PPMS who could not participate in ocrelizumab studies. Here, we report real-world patient characteristics and short-term safety data of patients with PPMS treated with ocrelizumab in this CUP. PATIENTS AND

METHODS:

This CUP was initiated in February 2017 - shortly before US Food and Drug administration approval in March 2017 - and ended in January 2018, following ocrelizumab approval in the EU. Adult patients (age ≥18 years) with PPMS who had a positive benefit/risk ratio according to the treating physician were eligible for inclusion at German treatment centres. The main exclusion criteria were current/recent treatment with other immune therapies and unresolved/chronic/active infections. Patients received methylprednisolone and an antihistamine before treatment with intravenous ocrelizumab in 6-month cycles. The first ocrelizumab dose was a 300 mg infusion followed by a second 300 mg infusion 2 weeks later; subsequent doses were delivered as a single 600 mg infusion. Adverse events were reported immediately.

RESULTS:

Of 580 requests received from 104 centres, 525 patients met the eligibility criteria. Thirty-five patients did not participate due to withdrawal by the treating physician, and one due to death prior to treatment. A total of 489 patients received at least one 600 mg dose of ocrelizumab (administered as two 300 mg infusions) and 51 received a second dose. Due to termination of the CUP upon marketing authorisation, the maximum follow-up period was 12 months. Median patient age was 52 years (range 24-73), and 49% were female. Previous immunomodulatory or immunosuppressive therapies had been received by 41% of patients, with the most commonly used being glucocorticoids, mitoxantrone, interferon-ß and glatiramer acetate. Patients with a previous malignancy, serious disease or infection (42 patients, 9%) had recovered from this prior to the CUP. Nine serious adverse events and 70 non-serious adverse events were reported in 40 patients. Adverse event categories were generally consistent with the known safety profile of ocrelizumab; one patient had carry-over progressive multifocal leukoencephalopathy (PML) due to previous natalizumab treatment.

CONCLUSION:

This CUP provides first real-world observations of ocrelizumab for the treatment of PPMS in a large patient cohort in Germany, supporting that ocrelizumab is generally well-tolerated in clinical practice. Physicians should be vigilant for early symptoms of PML, as to date, 9 PML cases that were all confounded have been reported in patients treated with ocrelizumab worldwide, with 8 carry-over cases from a prior DMT.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Crónica Progresiva / Anticuerpos Monoclonales Humanizados / Factores Inmunológicos Tipo de estudio: Clinical_trials Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Clin Neurol Neurosurg Año: 2020 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Esclerosis Múltiple Crónica Progresiva / Anticuerpos Monoclonales Humanizados / Factores Inmunológicos Tipo de estudio: Clinical_trials Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Clin Neurol Neurosurg Año: 2020 Tipo del documento: Article