Marcus D'Souza1, Athina Papadopoulou2, Michael Levy3, Anu Jacob4, Michael R Yeaman5, Tania Kümpfel6, Romain Marignier7, Friedemann Paul8, Alexander U Brandt9. 1. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Basel, CH, Switzerland. Electronic address: marcus.dsouza@usb.ch. 2. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Basel, CH, Switzerland. 3. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States. 4. The Walton Centre NHS Foundation Trust, Liverpool, United Kingdom; Department of MS an autoimmune neurology, Cleveland Clinic Abu Dabhi, United Arab Emirates. 5. Department of Medicine, Division of Molecular Medicine, Harbor-UCLA Medical Center; the David Geffen School of Medicine, University of California, Los Angeles, CA, United States; The Guthy-Jackson Charitable Foundation, Los Angeles, CA, United States. 6. Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center, Ludwig-Maximilians University Munich, Munich, D, Germany. 7. RM Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Lyon University Hospital, Lyon, F, France. 8. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 9. Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Neurology, University of California, Irvine, CA, United States.
Abstract
BACKGROUND: Currently, there is no evidence-based definition of attacks in neuromyelitis optica spectrum disorders (NMOSD). However, to allow their stringent use as valid endpoints, recent phase III trials in NMOSD defined criteria and adjudication of these events in context of these trials. The objective of this study was to investigate diagnostic procedures currently used in routine adjudication of suspected attacks in NMOSD, and to assess whether the standardized attack-criteria from two pivotal trials may be feasible in routine clinical care. METHODS: Four global clinical networks were surveyed using an online questionnaire: NEMOS (Neuromyelitis Optica Study Group), IMSVISUAL (International Multiple Sclerosis Visual System Consortium), GJCF-ICC (Guthy Jackson Charitable Foundation-International Clinical Consortium) and NOMADMUS (Devic's neuromyelitis optica and related neurological disorders study group). RESULTS: Seventy-eight responses were received from September 2018 to February 2019. Median annual number of patients seen with suspected attacks was 10 (range 2-130). Immediate access to MRI was reported by 59.0% of all participants and the majority performs an MRI for new patients with a myelitis, optic neuritis or other symptoms. In patients with established NMOSD diagnosis presenting during routine clinical visits only 10.5% or 9.2% always perform a brain or spinal cord MRI, respectively. Digital records of patients' visits are kept by 98.7% of all participants and 88.5% have direct access to case history. An expert neurological examination is performed for 94.9% of participants reported to perform an expert neurological examination in patients with acute attacs, while only 30.8% seem to perform the assessments according to the Neurostatus-Expanded Disability Status Scale (EDSS) definitions.. The Sakura Star study criteria which are based solely on clinical assessment could be feasible in routine care, provided that more centers use the Neurostatus-EDSS, while only 9% of participants fulfill all requirements for adjudication of the N-Momentum study criteria. CONCLUSIONS: The high percentage of centers using digital records is encouraging. However, routine adjudication of clinical events in NMOSD seems highly heterogeneous. MRI is the mainstay in the majority of queried centers, but its immediate availability is limited. Only a minority of centers are equipped for trial-grade classification of attacks, if this is not solely clinically based. Thus, standard and feasible guidelines for attack adjudication are urgently needed to standardize routine care, optimize future clinical trials and allow studying long-term safety and efficacy of newly approved drugs in phase IV trials.
BACKGROUND: Currently, there is no evidence-based definition of attacks in neuromyelitis optica spectrum disorders (NMOSD). However, to allow their stringent use as valid endpoints, recent phase III trials in NMOSD defined criteria and adjudication of these events in context of these trials. The objective of this study was to investigate diagnostic procedures currently used in routine adjudication of suspected attacks in NMOSD, and to assess whether the standardized attack-criteria from two pivotal trials may be feasible in routine clinical care. METHODS: Four global clinical networks were surveyed using an online questionnaire: NEMOS (Neuromyelitis Optica Study Group), IMSVISUAL (International Multiple Sclerosis Visual System Consortium), GJCF-ICC (Guthy Jackson Charitable Foundation-International Clinical Consortium) and NOMADMUS (Devic's neuromyelitis optica and related neurological disorders study group). RESULTS: Seventy-eight responses were received from September 2018 to February 2019. Median annual number of patients seen with suspected attacks was 10 (range 2-130). Immediate access to MRI was reported by 59.0% of all participants and the majority performs an MRI for new patients with a myelitis, optic neuritis or other symptoms. In patients with established NMOSD diagnosis presenting during routine clinical visits only 10.5% or 9.2% always perform a brain or spinal cord MRI, respectively. Digital records of patients' visits are kept by 98.7% of all participants and 88.5% have direct access to case history. An expert neurological examination is performed for 94.9% of participants reported to perform an expert neurological examination in patients with acute attacs, while only 30.8% seem to perform the assessments according to the Neurostatus-Expanded Disability Status Scale (EDSS) definitions.. The Sakura Star study criteria which are based solely on clinical assessment could be feasible in routine care, provided that more centers use the Neurostatus-EDSS, while only 9% of participants fulfill all requirements for adjudication of the N-Momentum study criteria. CONCLUSIONS: The high percentage of centers using digital records is encouraging. However, routine adjudication of clinical events in NMOSD seems highly heterogeneous. MRI is the mainstay in the majority of queried centers, but its immediate availability is limited. Only a minority of centers are equipped for trial-grade classification of attacks, if this is not solely clinically based. Thus, standard and feasible guidelines for attack adjudication are urgently needed to standardize routine care, optimize future clinical trials and allow studying long-term safety and efficacy of newly approved drugs in phase IV trials.
Authors: Alexander U Brandt; Friedemann Paul; Svenja Specovius; Hanna G Zimmermann; Frederike Cosima Oertel; Claudia Chien; Charlotte Bereuter; Lawrence J Cook; Marco Aurélio Lana Peixoto; Mariana Andrade Fontenelle; Ho Jin Kim; Jae-Won Hyun; Su-Kyung Jung; Jacqueline Palace; Adriana Roca-Fernandez; Alejandro Rubio Diaz; Maria Isabel Leite; Srilakshmi M Sharma; Fereshte Ashtari; Rahele Kafieh; Alireza Dehghani; Mohsen Pourazizi; Lekha Pandit; Anitha Dcunha; Orhan Aktas; Marius Ringelstein; Philipp Albrecht; Eugene May; Caryl Tongco; Letizia Leocani; Marco Pisa; Marta Radaelli; Elena H Martinez-Lapiscina; Hadas Stiebel-Kalish; Mark Hellmann; Itay Lotan; Sasitorn Siritho; Jérôme de Seze; Thomas Senger; Joachim Havla; Romain Marignier; Caroline Tilikete; Alvaro Cobo Calvo; Denis Bernardi Bichuetti; Ivan Maynart Tavares; Nasrin Asgari; Kerstin Soelberg; Ayse Altintas; Rengin Yildirim; Uygur Tanriverdi; Anu Jacob; Saif Huda; Zoe Rimler; Allyson Reid; Yang Mao-Draayer; Ibis Soto de Castillo; Michael R Yeaman; Terry J Smith Journal: BMJ Open Date: 2020-10-29 Impact factor: 2.692