Author: "Thouvenot E." / Topic: 03 medical and health sciences - Searchworks@Jio Institute Digital Library Search Results

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13 results on '"Thouvenot E."'

1. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Author: Leurs, CE, Twaalfhoven, HAM, Lissenberg-Witte, BI, van Pesch, V, Dujmovic, I, Drulovic, J, Castellazzi, M, Bellini, T, Pugliatti, M, Kuhle, J, Villar, LM, Alvarez-Cermeño, JC, Alvarez-Lafuente, R, Hegen, H, Deisenhammer, F, Walchhofer, LM, Thouvenot, E, Comabella, M, Montalban, X, Vécsei, L, Rajda, C, Galimberti, D, Scarpini, E, Altintas, A, Rejdak, K, Frederiksen, JL, Pihl-Jensen, G, Jensen, PEH, Khalil, M, Voortman, MM, Fazekas, F, Saiz, Albert, La Puma, D, Vercammen, M, Vanopdenbosch, L, Uitdehaag, BMJ, Killestein, J, Bridel, C, Teunissen, Charlotte E, Universitat Autònoma de Barcelona, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Basic (bio-) Medical Sciences, Ayşe, Altıntaş, Leurs, C.E., Twaalfhoven, H.A.M., Lissenberg-Witte, B.I., van Pesch, V., Dujmovic, I., Drulovic, J., Castellazzi, M., Bellini, T., Pugliatti, M., Kuhle, J., Villar, L.M., Alvarez-Cermeño, J.C., Alvarez-Lafuente, R., Hegen, H., Deisenhammer, F., Walchhofer, L.M., Thouvenot, E., Comabella, M., Montalban, X., Vécsei, L., Rajda, C., Galimberti, D., Scarpini, E., Rejdak, K., Frederiksen, J.L., Pihl-Jensen, G., Jensen, P.E.H., Khalil, M., Voortman, M.M., Fazekas, F., Saiz, A., La Puma, D., Vercammen, M., Vanopdenbosch, L., Uitdehaag, B.M.J., Killestein, J., Bridel, C., Teunissen, C., School of Medicine, Department of Neurology, Neurology, Laboratory Medicine, Epidemiology and Data Science, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Department of Anatomy and Neurosciences [Amsterdam, The Netherlands] (Amsterdam Neuroscience), Section Clinical Neuroanatomy [Amsterdam, The Netherlands], VU University Medical Center [Amsterdam]-VU University Medical Center [Amsterdam], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Cliniques Universitaires Saint-Luc [Bruxelles], Clinical Centre of Serbia, Università degli Studi di Ferrara (UniFE), University Hospital Basel [Basel], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Red Española de Esclerosis Múltiple (REEM), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Department of Neurology, Medical University of Innsbruck, Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'Esclerosi Múltiple de Catalunya (CemCat), Vall d'Hebron University Hospital [Barcelona], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Szeged [Szeged], Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Koç University, Medical University of Lublin, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Danish Multiple Sclerosis Research Centre, Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Department of Neurology, AZ Sint Jan Brugge Oostende, Neuroscience Amsterdam, VU University Medical Centre, 1081HV 1117, Amsterdam, Amsterdam Neuroscience [Pays-Bas], and Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam]
Subjects: KFLC (kappa free light chain), Adult, Male, Multiple Sclerosis, Clinical Neurology, Esclerosi múltiple, CSF, CSF (cerebrospinal fluid), Immunoglobulin light chain, Sensitivity and Specificity, NO, Multiple sclerosis, Immunoglobulin kappa-Chains, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, Immunoglobulin lambda-Chains, Humans, Medicine, Diagnostic biomarker, biomarkers, KFLC, OCB, 030304 developmental biology, 0303 health sciences, business.industry, Biochemical markers, Oligoclonal Bands, Reproducibility of Results, Middle Aged, OCB (oligoclonal IgG band), Free Light Chain, Biomarkers, Neurology, Multicenter study, Marcadors bioquímics, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Original Research Papers, 030217 neurology & neurosurgery, Kappa
Abstract: Objective: to validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: we performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: the cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2–138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5–22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85–0.90) was higher than OCB (0.82; 95%CI = 0.79–0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78–0.88) was lower (OCB = 0.92; 95% CI = 0.89–0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS., NA
Published: 2020

2. Radiologically Isolated Syndrome: 10-Year Risk Estimate of a Clinical Event

Author: Lebrun-Frenay, C., Kantarci, O., Siva, A., Sormani, M. P., Pelletier, D., Okuda, D. T., Azevedo, C., Amato, M. P., Bensa, C., Berger, E., Brochet, B., Ciron, J., Cohen, M., Inglese, M., Keegan, B. M., Labauge, P., Laplaud, D. -A., Le Page, E., Louapre, C., Makhani, N., Mathey, G., Mondot, L., Montalban, X., Pelletier, J., de Seze, J., Destefano, N., Thouvenot, E., Tintore, M., Tutuncuoglu, M., Uygunoglu, U., Vermersch, P., Weinshenker, B., and Zeydan, B.
Subjects: 0301 basic medicine, Adult, Male, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Time Factors, Adolescent, Journal Club, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, medicine, Humans, Young adult, Child, Event (probability theory), Aged, medicine.diagnostic_test, Clinical events, business.industry, Proportional hazards model, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, medicine.disease, Demyelinating Diseases, Female, Magnetic Resonance Imaging, Disease Progression, 030104 developmental biology, Risk Estimate, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract: Objective We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5-year risk for evolution from radiologically isolated syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10-year, multinational, retrospectively identified RIS dataset. Methods RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models. Results Additional follow-up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11-74 years), with a median clinical follow-up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium-enhanced lesions during follow-up was also associated with the risk of a seminal event. The reason for MRI and gadolinium-enhancing lesions at baseline did not influence the risk of a subsequent clinical event. Interpretation Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407-417.
Published: 2020

3. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults

Author: Cobo-Calvo, A., Ruiz, A., Maillart, E., Audoin, B., Zephir, H., Bourre, B., Ciron, J., Collongues, N., Brassat, D., Cotton, F., Papeix, C., Durand-Dubief, F., Laplaud, D., Deschamps, R., Cohen, M., Biotti, D., Ayrignac, X., Tilikete, C., Thouvenot, E., Brochet, B., Dulau, C., Moreau, T., Tourbah, A., Lebranchu, P., Michel, L., Lebrun-Frenay, C., Montcuquet, A., Mathey, G., Debouverie, M., Pelletier, J., Derache, N., Coustans, M., Rollot, F., De Seze, J., Vukusic, S., Marignier, R., Casey, D. R., Maze, D. M., Olaiz, D. J., Frangoulis, D. B., Debard, N., Vukusic, P. S., Zorila, D. C., Debouverie, P. M., Guillemin, P. F., Mathey, D. G., Ziegler, A., Edan, P. G., Le Page, D. E., Leray, D. E., Muraz, R., Brassat, P. D., Clanet, P. M., Peaureaux-Averseng, D. D., Dewas, C., Brochet, P. B., Ouallet, D. J., Ruet, D. A., Kounkou, K. K., De Seze, P. J., Collongues, D. N., Berthe, C., Vermersch, P. P., Hautecoeur, P. P., Deruelle, F., Papeix, D. C., Maillard, D. E., Lubetzki, P. C., Lebrun-Frenay, D. C., Cohen, D. M., Callier, C., Derache, D. N., Droulon, K., Labauge, P. P., Ayrignac, D. X., Carra-Dalliere, D. C., Pinna, F., Moreau, P. T., Fromont, D. A., Protin, A., Michel, D. L., Wiertlewski, D. S., Jousset, N., Berger, D. E., Chamard-Witkowski, D. L., Bereau, D. M., Cappe, C., Clavelou, P. P., Taithe, D. F., Moisset, D. X., Dumont, E., Pelletier, P. J., Audoin, P. B., Rico-Lamy, D. A., Di Lelio, B., Castelnovo, D. G., Stankoff, P. B., Giannesini, D. C., Heinzlef, D. O., Fagniez, D. O., Laage, D. C., Bourre, D. B., Lefaucheur, D. R., Maltete, D. D., Vimont, C., Al Khedr, D. A., Sehaki, S., Gout, D. O., Bensa, D. C., Cabre, P. P., Kasonde, D. I., Galli, P., Magy, P. L., Montcuquet, D. A., Nicol, M., Casez, D. O., Vaillant, D. M., Diop Kane, M., Camdessanche, P. J., Visneux, V., Guennnoc, D. A., Beltran, D. S., Meunier, G., Creange, P. A., Ayache, D. S., Abdellaoui, D. M., Pottier, D. C., Slesari, D. I., Sampaio, M., Deburghraeve?, D. V., Le Port, D., Ciron, D. J., Neau, P. J., Rabois, E., Labeyrie, D. C., Patry, D. I., Lescieux, E., Nifle, D. C., Servan, D. J., Pico, P. F., Chatagner, V., Camus-Jacqmin, D. M., Henry, D. C., Bottin, D. L., Castex, C., Diallo, S. S., Brisset, J. C., Cervenansky, F., Commovick, O., Defer, P. G., Durand-Dubief, D. F., Guttmann, P. C., Tourbah, P. A., Lifticariu, D. C., Constans, D. J., Tanguy, D. J., Dousset, P. V., Tourdias, D. T., Dardel, D. P., Oesterle, D. H., Gonin, D. S., Ricolfi, D. F., Grand, D. S., Krainik, D. A., Boncoeur-Martel, D. M., Ameli, D. R., Bonhomme, D. G., Cotton, P. F., Roch, D. J., Sappey-Marinier, D. D., Brunel, H., Coze, S., Girard, Nicolas, Lehmann, P., Ranjeva, P. J., Menjot De Champfleur, Nicolas, Anxionnat, P. R., Desal, D. H., Mondot, D. L., Savatovsky, D. J., Galanaud, P. D., Pyatigorskaya, D. N., Guillevin, D. R., Pierot, D. L., Barillot, D. C., Ferre, D. J., Bannier, E., Gerardin, D. E., Boutet, D. C., Kremer, D. S., Armspach, P. J., Berry, P. I., Bonneville, P. F., Dufay, N., Zephir, D. H., Gele, P., Marignier, D. R., Fiard, G., Lehmann, S., Lommazi, S., Laplaud, P. D., Gallot, G., Thouvenot, P. E., Fontaine, P. B., Rebeix, I., Desille-Dugast, M., CHU Pitié-Salpêtrière [APHP], Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de Hautepierre [Strasbourg], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de Neurologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-IFR70-CHU Pitié-Salpêtrière [APHP], Department of Neurology, CHU Lyon, Centre Hospitalier Universitaire de Nice (CHU Nice), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Reims (CHU Reims), Observatoire astronomique de Strasbourg (ObAS), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), The Functional Electrical Neuroimaging Laboratory, Université de Lausanne (UNIL), Department of Economics, École Polytechnique, Palaiseau Cedex, 91128, France, affiliation inconnue, Alimentation et sciences sociales (ALISS), Institut National de la Recherche Agronomique (INRA), CHU Marseille, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, ISL, Laboratoire Charles Coulomb (L2C), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Instituto de Tecnologia Ceramica, Universitat Jaume I, CHU Grenoble, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Neurologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, medicine.medical_specialty, Visual acuity, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, business.industry, Hazard ratio, Encephalopathy, Myelitis, Retrospective cohort study, Lower risk, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, medicine, Optic neuritis, Neurology (clinical), medicine.symptom, 10. No inequality, business, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, Survival analysis
Abstract: ObjectiveTo describe clinical and radiologic features associated with myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in a large French nationwide adult cohort, to assess baseline prognostic features of MOG-Ab-associated diseases after a first acute demyelinating syndrome, and to evaluate the clinical value of MOG-Ab longitudinal analysis.MethodsClinical data were obtained from 197 MOG-Ab-positive patients ≥18 years of age. Complete imaging data were available in 108, and 54 serum samples were eligible for longitudinal evaluation. For survival analysis comparison, 169 aquaporin-4 antibody (AQP4-Ab)-positive patients from the NOMADMUS database were included.ResultsMedian age at onset was 36.46 (range 18.0–76.8) years, and patients were predominantly white (92.9%) with male:female ratio, 1.1. Clinical phenotype at onset included optic neuritis or myelitis in 90.86%, isolated brainstem or encephalopathy syndromes in 6.6%, and a combination of syndromes in 2.5%. Distinctive brain MRI findings in MOG-Ab-positive patients were thalamic and pontine lesions. Cortical and leptomeningeal lesions were found in 16.3% and 6.1%, respectively. The probability of reaching a first relapse after 2 and 5 years was 44.8% and 61.8%, respectively. MOG-Ab-positive patients were at lower risk at presentation of further clinical relapse (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.26–0.79) compared to AQP4-Ab-positive individuals. MOG-Ab-positive individuals had a lower risk of reaching Disability Status Scale score of 3.0 (HR 0.46, 95% CI 0.22–0.94) and visual acuity of 20/100 (HR 0.23, 95% CI 0.07–0.72). Finally, MOG-Ab titers were higher at relapse than in remission (p = 0.009).ConclusionIn adults, MOG-Ab-associated disease extends beyond clinical and radiologic abnormalities in the optic nerve and spinal cord. Despite the relapsing course, the overall visual and motor outcome is better compared with AQP4-Ab-positive patients.
Published: 2018

4. Rivaroxaban for stroke prevention after embolic stroke of undetermined source

Author: Hart, Robert G, Sharma, Mukul, Mundl, Hardi, Kasner, Scott E, Bangdiwala, Shrikant I, Berkowitz, Scott D, Swaminathan, Balakumar, Lavados, Pablo, Wang, Yongjun, Wang, Yilong, Davalos, Antonio, Shamalov, Nikolay, Mikulik, Robert, Cunha, Luis, Lindgren, Arne, Arauz, Antonio, Lang, Wilfried, Czlonkowska, Anna, Eckstein, Jens, Gagliardi, Rubens J, Amarenco, Pierre, Ameriso, Sebastian F, Tatlisumak, Turgut, Veltkamp, Roland, Hankey, Graeme J, Toni, Danilo, Bereczki, Daniel, Uchiyama, Shinichiro, Ntaios, George, Yoon, Byung-Woo, Brouns, Raf, Endres, Matthias, Muir, Keith W, Bornstein, Natan, Ozturk, Serefnur, O'Donnell, Martin J, De Vries Basson, Matthys M, Pare, Guillaume, Pater, Calin, Kirsch, Bodo, Sheridan, Patrick, Peters, Gary, Weitz, Jeffrey I, Peacock, W Frank, Shoamanesh, Ashkan, Benavente, Oscar R, Joyner, Campbell, Themeles, Ellison, Connolly, Anderson DC, Stuart J., Demets, Dl, Kaste, M, Norrving, B, Wyse, Dg, Alet, M, Allende, G, Beinlich, A, Berrios, W, Bruera, G, Castro, D, Chialvo, L, Claverie, S, Contardo, L, Couto, J, Deganutto, R, Diaz, R, Dossi, D, Esnaola, M, Falco, M, Fernandez Pirrone, P, Ferrari, J, Firstenfeld, A, Galli Giqueauk, E, Gilli, M, Gonzalez, L, Gonzalez Toledo, M, Grecco, M, Halac, B, Hawkes, M, Ioli, P, Jure, L, Klein, F, Lepera, S, Lujan, S, Mackinnon, F, Marroquin, M, Martin, J, Parisi, V, Perez Leguizamon, P, Persi, G, Povedano, P, Povedano, G, Pujol Lereis, V, Radrizzani, L, Reich, E, Repetto, M, Rodriguez Lucci, F, Romano, M, Saredo, G, Schneider, M, Simonsini, C, Sumay, G, Thomson, A, Toledo, W, Torres, C, Vila, A, Abdul Rasheed, N, Anderson, C, Bailey, P, Blacker, D, Carcel, C, Clissold, B, Delcourt, C, Field, D, Gangadharan, S, Ghia, D, Kleinig, T, Leyden, J, Ly, J, Ma, H, Mackey, E, Mishra, S, Moey, A, Musuka, T, Pepper, E, Phan, T, Sabet, A, Saw, J, Singh, B, Tryambake, D, Tu, H, Wijeratne, T, Wong, A, Augustin, S, Esterbauer, M, Garnauf, M, Gasiorek, K, Gasser, S, Gaugg, M, Greisenegger, S, Harrasser, M, Heine, M, Huber, B, Joachim, B, Kapeller, P, Krebs, S, Kreuzpointer, R, Kunzmann, J, Lechner, H, Lohninger, B, Luschin, G, Macher, S, Marko, M, Matosevic, B, Mayr, A, Mismas, A, Mitrovic, N, Mutzenbach, J, Oberndorfer, S, Obmann, S, Raffelsberger, T, Roesler, C, Salletmayr, T, Serles, W, Stadler, K, Tinchon, A, Tolino, M, Verocai, V, Vigl, M, Voglsperger, B, Weber, J, Werner, P, Windt, J, Winkler, A, Wurzinger, H, Zelenka, I, Cras, P, Crols, R, De Keyser, J, De Klippel, N, De Pauw, A, De Smedt, A, Dhollander, I, Hermans, S, Ligot, N, Maqueda, V, Maqueda Maqueda, V, Naeije, G, Seynaeve, L, Soors, P, Van Daele, W, Vanacker, P, Vanderschueren, G, Willems, C, Yperzeele, L, Avelar, W, Bacellar, A, Batista, C, Bazan, R, Braga, G, Cardoso, F, Dagnino, M, Fabio, S, Ferreira Junior, G, Freitas, G, Friedrich, M, Gomes Neto, A, Guarda, S, Katsurayama, M, Machado, M, Martins, S, Meira, F, Minelli, C, Morais, R, Moro, C, Neto, O, Polin, M, Silva, D, Weiss, G, Basile, V, Beaudry, M, Berlingieri, J, Blacquiere, D, Buck, B, Chan, R, Coutts, S, Das, S, Desai, J, Ehrensperger, E, Field, T, Gladstone, D, Hachinski, V, Hassan, A, Hegedus, J, Hill, M, Jin, A, Khaw, A, Mackey, A, Maclean, G, Mandzia, J, Mann, S, Mehdiratta, M, Murphy, C, Ng, K, Oczkowski, W, Penn, A, Perera, K, Perez, Y, Pesant, Y, Phillips, S, Poppe, A, Sahlas, J, Shuaib, A, Spence, D, Sposato, L, Stotts, G, Tamayo, A, Teal, P, Wilson, L, Winder, T, Yegappan, C, Yip, S, Andreu, D, Araya, P, Bustamante, G, Figueroa, C, Gasic, K, Herrero, D, Matamala, G, Munoz, S, Olavarria, V, Pasten, J, Polanco, J, Reyes, P, Roldan, A, Salamanca, P, Silva, P, Toloza, C, Verdugo, M, Cai, K, Che, C, Chen, J, Chen, Z, Chen, T, Chen, H, Chen, X, Chen, B, Chen, G, Chen, L, Chu, F, Cui, L, Dai, C, Ding, N, Ding, J, Du, P, Du, J, Fang, L, Feng, J, Gao, Y, Geng, J, Guan, J, Hao, L, Huang, D, Huang, H, Jin, X, Jing, P, Ke, K, Li, G, Li, M, Li, S, Li, J, Liang, Z, Lin, H, Liu, K, Liu, X, Lu, Z, Ma, C, Pei, H, Qiu, J, Qu, X, Shen, W, Sun, X, Tian, J, Tong, L, Tong, Z, Wang, J, Wang, L, Wang, X, Wang, W, Wang, N, Wang, D, Wang, H, Wen, G, Weng, G, Wu, W, Wu, S, Xiao, B, Xiaopeng, W, Xiong, L, Xiong, Y, Xu, Y, Xu, J, Xu, Z, Yang, L, Yang, Y, Yang, X, Yang, J, Yang, Q, Yang, B, Zhang, C, Zhang, B, Zhang, Y, Zhang, S, Zhang, M, Zhang, X, Zhang, J, Zhao, L, Zhou, L, Bar, M, Barteys, M, Bartolottiova, T, Carek, M, Ferencova, K, Fiksa, J, Gallo, J, Goldemund, D, Hanouskova, L, Herzig, R, Hon, P, Jankovych, J, Jura, R, Kadlcikova, J, Kemlink, D, Kopecky, S, Krajickova, D, Kral, M, Krejci, V, Pavlik, O, Peisker, T, Pernicka, M, Peska, S, Rapantova, P, Reif, M, Rekova, P, Sanak, D, Sebejova, M, Skoda, O, Slonkova, J, Stetkarova, I, Tenora, D, Tumova, R, Vaclavik, D, Vasko, P, Veverka, T, Vitkova, E, Volna, J, Andersen, G, Christensen, H, Christensen, T, Damgaard, D, Iversen, H, Krarup Hansen, C, Kruuse, C, Martinussen, M, Modrau, B, Murtuzova, A, Ovesen, C, Papina, M, Svaneborg, N, Von Weitzel-Mudersbach, P, Curtze, S, Fanta, S, Huhtakangas, J, Keskinarkaus, I, Kivioja, R, Koivu, M, Korpela, J, Larjo, T, Linna, M, Marinkovic, I, Martinez-Majander, N, Nieminen, T, Nikkanen, M, Numminen, H, Ortiz, R, Österlund-Tauriala, E, Roine, R, Roine, S, Ruuskanen, J, Saarinen, J, Shulga, A, Sibolt, G, Tapanainen, A, Tapiola, T, Tiainen, M, Tomppo, L, Tumpula, O, Tuomainen, P, Tynkkynen, J, Vainikka, S, Valpas, J, Virta, J, Ylikallio, E, Ylikotila, P, Accassat, S, Aniculaesei, A, Baronnet, F, Bejot, Y, Bindila, D, Birchenall, J, Blanc-Labarre, C, Bodiguel, E, Bouly, S, Cabrejo, L, Calvet, D, Corlobe, A, Crozier, S, Delpont, B, Deltour, S, Diaconu, M, Domigo, V, Epinat, M, Ferreira, A, Fisselier, M, Garnier, P, Gimenez, L, Gueguen, A, Guidoux, C, Guillon, B, Guiraudg, V, Hervieu-Begue, M, Hobeanu, M, Khoumri, C, Lamy, C, Lauer, V, Le Bouc, R, Lecouturier, K, Leder, S, Leger, A, Macian-Montoro, F, Meseguer, E, Morar-Precup, D, Morvan, T, Morvan, E, Obadia, M, Osseby, G, Philippi, S, Pico, F, Quenardelle, V, Reiner, P, Rigual, R, Rosso, C, Sabben, C, Samson, Y, Sevin, M, Sibon, I, Thouvenot, E, Timsit, S, Touze, E, Turc, G, Vahedi, K, Varvat, J, Wacongne, A, Wolff, V, Yalo, B, Zinchenko, I, Bagelmann, H, Bardutzky, J, Barlinn, J, Bathe-Peters, R, Berrouschot, J, Dietzel, J, Ehrlich, S, Fatar, M, Filipov, A, Fluri, F, Gabriel, M, Geran, R, Gliem, M, Graf, S, Griebe, M, Grosse, G, Haeusler, K, Harmel, P, Held, V, Hellwig, S, Henkner, J, Hieber, M, Hoyer, C, Jander, S, Keilitz, J, Kellner, J, Knecht, S, Koch, M, Koehler, L, Kucken, D, Kusnick, G, Lambeck, J, Lee, J, Leisse, I, Lubke-Detring, S, Machetanz, J, Mensch, A, Meyer, N, Molis, A, Mueller, T, Muhl, C, Nave, A, Radtke, A, Roth, Y, Roukens, R, Schlachetzki, F, Schneider, I, Schuppner, R, Schurig, J, Schwarzbach, C, Seidel, G, Sonntag, N, Steinert, S, Stoll, A, Stumpp, A, Taggeselle, J, Trommer, A, Tuetuencue, S, Wartenberg, K, Weissenborn, K, Wittayer, M, Wolf, M, Wolter, C, Worthmann, H, Wunderlich, S, Zitzmann, A, Anagnostou, E, Brokalaki, C, Hatzitolios, A, Kakaletsis, N, Kanellos, I, Kei, A, Korompoki, E, Koutroubi, A, Liamis, G, Makaritsis, K, Manios, E, Michas, F, Milionis, H, Papadopoulos, G, Papadopoulou, E, Papagiannis, A, Polychronopoulou, E, Sagris, D, Satsoglou, S, Savopoulos, C, Solganov, I, Spengos, K, Stamatelopoulos, K, Terentiou, A, Tountopoulou, A, Vassilopoulou, S, Amjad, A, Balazs, A, Bankuti, Z, Bicsak, T, Borcsik, L, Csanyi, A, Csiba, L, Csontos, K, Csuha, R, Czurko, M, Danku, V, Dioszeghy, P, Faust, K, Fazekas, F, Gerocs, Z, Gottschal, M, Gyuker, N, Hajas, A, Horvath, L, Horvath, M, Iljicsov, A, Jakab, K, Javor, L, Kakuk, I, Karasz, O, Kasa, K, Kasza, J, Kerekgyarto, M, Klivenyi, P, Kovacs, K, Kovacs, T, Kovacs, H, Lajos, B, Lovasz, R, Magyar, T, Matoltsy, A, May, Z, Molnar, S, Monosi, C, Motko, T, Nemeth, R, Nemeth, L, Nikl, J, Olah, L, Orosz, V, Panczel, G, Pentek, S, Prendl, B, Rozsa, C, Rum, G, Sas, K, Sas, A, Semjen, J, Simony, Z, Sipos, I, Szabo, K, Szasz, G, Szegedi, N, Szekely, A, Szilagyi, G, Szoboszlai, K, Szpisjak, L, Toth, G, Uhrinyakova, L, Valikovics, A, Varga, Z, Vass, L, Vastagh, I, Vecsei, L, Zboznovits, D, Coveney, S, Horgan, G, Kelly, P, Murphy, S, Smyth, A, Waters, R, Abu Ahmad, F, Bloch, S, Dorodnicov, E, Hallevi, H, Haratz, S, Horev, A, Kolianov, V, Leker, R, Mahagney, A, Marzelik, O, Rephaeli, G, Tanne, D, Weller, B, Acciarresi, M, Adami, A, Agostoni, E, Alemseged, F, Altavilla, R, Angelocola, S, Anticoli, S, Berardi, V, Bravi, M, Candeloro, E, Cappellari, M, Carletti, M, Caruso, P, Castellini, P, Cavallini, A, Cenciarelli, S, Cerrone, P, Condurso, R, Consoli, D, Danese, A, Della Marca, G, Denaro, M, Di Mascio, M, Diomedi, M, Distefano, M, Frisullo, G, Furlanis, G, Galati, F, Gallina, A, Gallinella, E, Giannandrea, D, Giatsidis, F, Greco, L, Impellizzeri, M, Landolfi, A, Lanfranconi, S, Latte, L, Lembo, G, Longoni, M, Marando, C, Marini, C, Marsili, E, Mastrocola, S, Mazzoli, T, Melis, M, Micheletti, N, Moller, J, Monzani, V, Naccarato, M, Paciaroni, M, Padiglioni, C, Persico, A, Pezzella, F, Pieroni, A, Piras, V, Postorino, P, Pozzerese, C, Profice, P, Ricci, S, Rinaldi, C, Rizzato, B, Rocco, A, Roveri, L, Santalucia, P, Semerano, A, Sicilia, I, Silvestrini, M, Sucapane, P, Tomelleri, G, Tropepi, D, Venti, M, Amino, T, Chin, M, Deguchi, I, Fujigasaki, H, Fukuyama, K, Haraguchi, K, Hasegawa, Y, Hattori, M, Hayashi, T, Hirose, M, Honma, Y, Igarashi, S, Irie, S, Itabashi, R, Ito, Y, Kamata, T, Kaneko, C, Kawanishi, M, Kimura, R, Kitagawa, K, Kobayashi, Y, Kondo, T, Kuwashiro, T, Matsumoto, S, Miyake, H, Nagakane, Y, Nishino, S, Nishiyama, Y, Nogawa, S, Ochiai, J, Ohira, M, Okamoto, Y, Okubo, S, Okuda, S, Ooyama, K, Sakai, N, Suenaga, T, Suzuki, H, Takamatsu, K, Takao, M, Taki, W, Takizawa, S, Tokunaga, K, Toyoda, K, Urui, S, Yamada, T, Yamasaki, M, Yoshida, Y, Yuasa, H, Bae, H, Cha, J, Chang, D, Chung, C, Heo, J, Hong, K, Kim, J, Lee, B, Nah, H, Oh, K, Park, M, Park, J, Rha, J, Sohn, S, Amaya Sanchez, L, Arauz Gongora, A, Cantu Brito, C, Chiquete Anaya, E, Felipe Amaya, P, Fernandez Vera, J, Garcia Lopez, R, Gien Lopez, J, Gongora-Rivera, J, Hernandez, J, Leal Cantu, R, Lopez Garza, N, Medina Pech, C, Mendez, B, Pena Sedna, L, Reyes Morales, S, Ruiz Franco, A, Serrano, F, Tovar, M, Uribe, R, Bak, Z, Baranowska, A, Bilik, M, Blazejewska-Hyzorek, B, Brola, W, Brzoska-Mizgalska, J, Buksinska-Lisik, M, Chorazy, M, Czerska, M, Czuryszkiewicz, M, Dalek, G, Dylewicz, L, Fiszer, U, Fraczek, A, Friedman, A, Fryze, W, Gasecki, D, Gębura, K, Geremek, M, Glabinski, A, Gluszkiewicz, M, Goździk, I, Grzesik, M, Jasek, L, Kaczorowska, B, Kalinowska, K, Kaminska, K, Kapica-Topczewska, K, Karlinski, M, Kobayashi, A, Kosarz-Lanczek, K, Kowalczyk, K, Kowalska, M, Kraska, J, Krzyzanowska, M, Kulakowska, A, Kurkowska-Jastrzebska, I, Lasek-Bal, A, Litwin, T, Morton, M, Myśliwy, W, Nosek, K, Nowak, B, Nowakowska-Śledź, E, Odyniec, A, Oleszek, J, Ozdoba-Rot, J, Palasik, W, Pawelczyk, M, Rozanski, D, Rozniecki, J, Sawicka, M, Sieczkowska, E, Skowron, P, Skowronska, M, Sliwinska, B, Sobolewski, P, Sobota, A, Stoiński, J, Szczuchniak, W, Szczyrba, S, Szewczyk, Z, Szlufik, S, Tarasiuk, J, Tutaj, A, Uchwat, U, Wach-Klink, A, Winska-Tereszkiewicz, A, Wisniewska, A, Włodek, A, Wojnarowska-Arendt, A, Zalewska, J, Zielinska-Turek, J, Ziomek, M, Zwiernik, J, Abreu, P, E Silva A, Amaral, Azevedo, E, Barroso, C, Calejo, M, Campillo, J, Campos Costa, E, Coelho, J, Correia, M, Correia, C, Gregorio, T, Lopes, D, Machado, C, Mendonca, T, Pereira, L, Pidal, A, Pineiro, S, Pinto, A, Ribeiro, J, Rodrigues, M, Salgado, P, Salgado, A, Santo, G, Sargento, J, Varela, R, Abroskina, M, Badalyan, K, Balueva, T, Barulin, A, Bazhenova, O, Belkin, A, Bogdanov, E, Daineko, A, Druzenko, I, Fedin, A, Fidler, M, Gogoleva, E, Golikov, K, Gonysheva, Y, Greshnova, I, Guryanova, N, Gusev, V, Kashaeva, E, Kaygorodtseva, S, Khairutdinova, D, Kholopov, M, Kirpicheva, S, Koltsov, I, Konkov, I, Kurenkova, N, Kurtenkova, N, Kurushina, O, Kustova, M, Lagutenko, M, Lenskaya, L, Lupinogina, L, Lvova, A, Melnikova, E, Meshkova, K, Morozova, E, Mozhejko, E, Nikoforova, M, Obrezan, A, Ondar, V, Pizova, N, Polyakov, A, Popov, D, Prazdnichkova, E, Prokopenko, S, Pudov, E, Salnikov, M, Samoshkina, O, Semushina, D, Shchukin, I, Shepeleva, E, Shmonin, A, Smolkin, A, Soldatov, M, Soloveva, L, Solovyeva, E, Stakhovskaya, L, Tcvetkova, S, Varvyanskaya, N, Voznyuk, I, Zhirnova, O, Ahmed, F, Basson, M, Engelbrecht, J, Hobson, B, Jansen, J, Nel, J, Nell, H, Njovane, X, Pretorius, M, Roos, J, Salig, S, Siebert, M, Amaro, S, Arenillas Lara, J, Arias Rivas, S, Baez Martinez, E, Bas, M, Bashir, S, Bragado, I, Cajaraville, S, Camps, P, Cardona Portela, P, Casado-Naranjo, I, Castellanos, M, Cayuela Caudevilla, N, Chamorro, A, Constantino Silva, A, Cortijo Garcia, E, De La Torre, J, De Torres, R, Diaz Otero, F, Diez-Tejedor, E, Escribano, B, Escudero, I, Fernandez, M, Font, M, Fortea, G, Freijo, M, Fuentes Gimeno, B, Gamero, M, Garcia, J, Garcia Pastor, A, Garcia Sanchez, S, Geniz Clavijo, M, Gil Nunez, A, Giralt, E, Gomez-Choco, M, Gomis, M, Gutiérrez, R, Iglesias Mohedano, A, Lago, A, Lara Lezama, L, Lara Rodriguez, B, Llull, L, Lopez Fernandez, M, Lorenzo, A, Maestre-Moreno, J, Marta Moreno, J, Marti-Fabregas, J, Martínez Sánchez, P, Mauri Cabdevila, G, Mengual Chirifie, J, Molina, C, Molina, J, Moniche, F, Morales, L, Morales, A, Nombela, F, Núñez, F, Pagola, J, Perez, S, Portilla, J, Prats, L, Purroy, F, Quesada Garcia, H, Ramirez Moreno, J, Redondo Robles, L, Renu, A, Riveira Rodriguez, C, Roa, A, Rodriguez Campello, A, Rodriguez Pardo De Donlebun, J, Rodriguez Yanez, M, Rudilosso, S, Ruiz Ares, G, Sànchez Cerón, M, Santamaria Cadavid, M, Sanz Cuesta, B, Serena, J, Silva, Y, Soriano Soriano, C, Tejada Garcia, J, Tejada Meza, H, Tembl, J, Terceno, M, Trillo, S, Urra, X, Usero Ruiz, M, Vazquez, P, Vilar, C, Villanueva Osorio, J, Ximenez-Carrillo, A, Zapata, E, Esbjornsson, M, Karlsson, J, Kremer, C, Kuris, A, Staaf, G, Stiehm, M, Timberg, I, Tossavainen, C, Wester, P, Arnold, M, Baumgartner, P, Beer, J, Bicker, H, Boos, L, Cereda, C, Chaloulos-Iakovidis, P, Christian, L, Engelter, S, Fisch, L, Fischer, U, Frey, S, Frick, M, Hauk, M, Hoffmann, M, Kahles, T, Manno, C, Medlin, F, Mircea, D, Nedeltchev, K, Panos, L, Polymeris, A, Schillinger, N, Stocker, R, Sztajzel, R, Alaydin, H, Batur Caglayan, H, Colakoglu, S, Demirci, N, Duman, T, Eren, F, Gokce, M, Inanc, Y, Nazliel, B, Ongun, G, Ozcekic Demirhan, S, Ozyurt, E, Selcuk, D, Sorgun, M, Tezcan, S, Togay Isikay, C, Tokgoz, O, Ulku Acar, R, Uluduz Ugurlu, D, Abdul-Saheb, M, Ahmad, N, Ali, A, Alwis, L, Balogun, I, Bathula, R, Behnam, Y, Bhandari, M, Bhargavah, M, Black, T, Blank, C, Bruce, D, Burn, M, Canepa, C, Chakrabarti, A, Chandrasena, D, Chembala, J, Cheripelli, B, Clarke, R, Cohen, D, Collas, D, Constantin, C, Dani, K, Del Giudice, A, Dennis, M, Devine, J, Dima, S, Doubal, F, Duodu, Y, Dutta, D, El Ta Wil, S, Elyas, S, Evans, N, Eveson, D, Fotherby, K, France, E, Furnace, J, Grabowski, S, Gunathilagan, G, Gutierrez, R, Guyler, P, Hargroves, D, Harkness, K, Harvey, M, Hayhoe, H, Hicken, L, Hussain, M, Kelly, S, Lam, M, Lindert, R, Louw, S, Luder, R, Macleod, M, Majid, A, Mangion, D, Markova, S, Markus, H, Marsh, R, Mcarthur, K, Menon, N, Metcalf, K, Minhas, J, Minns, M, Mistri, A, Moreton, F, Mpelembue, M, Muddegowda, G, Mudhar, O, Musarrat, K, Myint, M, Natarajan, I, Naylor, D, Ngeh, J, Papavasileiou, V, Perry, R, Piechowski-Jozwiak, B, Pradhan, M, Rani, A, Rashed, K, Robinson, T, Roffe, C, Saksena, R, Sattar, N, Sekaran, L, Selvarajah, J, Shah, S, Sinha, D, Sivakumar, R, Sztriha, L, Walters, D, Webb, T, Werring, D, Whiteley, W, Whiting, R, Abdelhamid, N, Abdul Rahman, D, Amin, H, Androulakis, M, Babikian, V, Baker, M, Barker Trejo, S, Benjamin, A, Birnbaum, L, Burke, J, Chen, S, Clark, W, Coull, B, De Havenon, A, Dearborn, J, Degeorgia, M, Essa, B, Fares, M, Favate, A, Furlan, A, Gebreyohanns, M, Goddeau, R, Green, D, Greer, D, Haralur Sreekantaiah, Y, Hasan, R, Hedna, V, Henninger, N, Holmstedt, C, Ishida, K, Jagolino, A, Johnson, M, Jun-Oconnell, A, Kaur, S, Khanna, A, Kirshner, H, Kittner, S, Kleindorfer, D, Leira, E, Loomis, C, Lord, A, Lowenkopf, T, Lutsep, H, Magadan, A, Majjhoo, A, Maud, A, Mayasi, Y, Mccullough, L, Mckinney, J, Mehta, S, Mehta, D, Mehta, B, Messe, S, Miller, B, Milling, T, Moonis, M, Navaratnam, D, Okpala, M, Patel, N, Pettigrew, L, Phinney, T, Ramos-Estebanez, C, Rasmussen, J, Rodriguez, G, Rybinnik, I, Santiago, P, Sarraj, A, Savitz, S, Sawyer, R, Scandura, T, Schindler, J, Sen, S, Shang, T, Sharrief, A, Sila, C, Simpkins, A, Sundararajan, S, Talahma, M, Tayal, A, Thaler, D, Tirschwell, D, Torres, J, Vora, N, Warnack, W, Waters, M, Wilson, C, Xiong, W, Zweifler, R, Zanferrari, C., St Marys Development Trust, Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Department of Neurology (Dep Neuro - BEIJING), Tiantan Hospital, Neurology department, Universidade de Coimbra [Coimbra], Department of Internal Medicine, University Hospital Basel [Basel], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurological Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Neurology, Seoul National University Hospital, Institute of Neurosciences and Psychology [Glasgow], University of Glasgow, Neurology Department, Ichilov Medical Center, CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Yperzeele, Laetitia, NAVIGATE ESUS Investigators, and Selçuk Üniversitesi
Subjects: Stroke/etiology, Male, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Brain Ischemia, Brain ischemia, 0302 clinical medicine, DESIGN, Rivaroxaban, Hemorrhage/chemically induced, Secondary Prevention, Medicine, Factor Xa Inhibitors/adverse effects, Stroke, Rivaroxaban/adverse effects, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, Aspirin, Atrial fibrillation, General Medicine, FORAMEN OVALE CLOSURE, Middle Aged, TRIALS, Intracranial Embolism, SAFETY, Aged, Factor Xa Inhibitors, Female, Hemorrhage, Humans, Platelet Aggregation Inhibitors, Medicine (all), Cardiology, Foramen ovale closure, Platelet aggregation inhibitor, Settore MED/26 - Neurologia, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Platelet Aggregation Inhibitors/adverse effects, ANTITHROMBOTIC THERAPY, Aspirin/adverse effects, WARFARIN, 03 medical and health sciences, Secondary Prevention/methods, Medicine, General & Internal, Internal medicine, Intracranial Embolism/drug therapy, General & Internal Medicine, NAVIGATE ESUS Investigators, METAANALYSIS, Science & Technology, CRYPTOGENIC STROKE, business.industry, Warfarin, medicine.disease, EFFICACY, ATRIAL-FIBRILLATION, Human medicine, business, Brain Ischemia/prevention & control, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: WOS: 000434263000007, PubMed: 29766772, BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P, BayerBayer AG; Janssen Research and Development, Supported by Bayer and Janssen Research and Development.
Published: 2018

5. Epstein-Barr-negative MS: a true phenomenon?

Author: Dobson, Ruth, Kuhle, Jens, Middeldorp, Jaap, Giovannoni, Gavin, on behalf of the international CIS study investigators including Dalla Costa, G, Furlan, R, Martinelli, V, Comi, G, Runia, T, Hintzen, R, Evdoshenko, E, Lazareva, N, Lapin, S, Thouvenot, E, Lehmann, S, Castelnovo, G, Iaffaldano, P, Direnzo, V, Trojano, M, Khademi, . M, Piehl, F, Olsson, T, Comabella, M, Montalban, X, Tintoré, M, Sombekke, M, Killestein, J, Teunissen, C, Hegen, H, Deisenhammer, F, Rauch, S, D'Alfonso, S, Barizzone, N, Alvarez Cermeño, Jc, Villar, Lm, Kleinová, P, Horáková, D, Havrdová, E, Roesler, R, Lauda, F, Tumani, H, Llufriu, S, Villoslada, P, Saiz, A, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Siva, A, Menge, T, Kieseier, Bc, Hartung, Hp, Rajda, C, Vécsei, L, Bergamaschi, R, Colombo, E, Franciotta, D, Moll, N, Pelletier, J, Picard, C, Khalil, M, Enzinger, C, Fuchs, S, Marignier, R, Confavreux, C, Dujmovic, I, Drulovic, J, Larsson, H, Malmestrom, C, Lycke, J, Scarpini, E, C. Fenoglio, C, Galimberti, D, Wergeland, S, Torkildsen, Ø, Myhr, Km, Laroni, Alice, Uccelli, Antonio, Annibali, V, Romano, S, Salvetti, M, Martínez, Ad, Carra, A, Rejdak, K, Frederiksen, Jl, Brassat, D, Bosca, I, Casanova, B, Derfuss, T, Lindberg, R, Yaldizli, Ö, Kappos, L, Leone, M., and Pathology
Subjects: 0301 basic medicine, business.industry, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Neurology, Epstein barr, Phenomenon, Medicine, Neurology (clinical), business, Competence (human resources), Social psychology, Clinical/Scientific Notes, 030217 neurology & neurosurgery
Abstract: This work was supported by institutional funding and in part by the BMBF grant KKNMS (Competence Net Multiple Sclerosis) to H Tumani.
Published: 2017

6. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Author: Ridker, P. M., Revkin, J., Amarenco, P., Brunell, R., Civeira, F., Flather, M., Glynn, R. J., Gregoire, J., Jukema, J. W., Karpov, Y., Kastelein, J. J. P., Koenig, W., Lorenzatti, A., Manga, P., Masiukiewicz, U., Miller, M., Mosterd, A., Murin, J., Nicolau, J. C., Nissen, S., Ponikowski, P., Santos, R. D., Schwartz, P. F., Soran, H., White, H., Wright, R. S., Vrablik, M., Yunis, C., Shear, C. L., Tardif, Conde D, J. -C., Colquhoun, D, Missault, L, Grégoire, J, Gao, R, Urina, M, Solar, M, Jensen, Hk, Grobbee, D, Savolainen, M, Schiele, Fn, Montalescot, G, Edes, I, Blake, G, Lotan, C, Maggioni, A, Savonitto, S, Lee, Cw, Leiva Pons JL, Dan, Ga, Cortada, Jb, Mellbin, L, Kahan, T, Noble, S, Hwang, Jj, Sritara, P, Tökgozoğlu, L, Tarasenko, L, Borer, Js, Black, H, Carmena, R, Furie, Kl, Mcmurray, J, Neaton, J, Zannad, F, O’Neill, B, Welty, F, Mcnamara, R, Chun, H, Abbott, Jd, Jacoby, D, Mcpherson, C, Jadbabaie, F, Pinto, D, Mccullough, L, Silverman, Ie, Sansing, Lh, Dearborn-Tomazos, J, Foody, J, Schindler, J, Piazza, G, Chakrabarti, A, Pride, Y, Gelfand, E, Baultrukonis, D, Chaudhuri, S, Frederich, R, Johnson, M, Mridha, K, Powell, C, Wang, E, Wei, C, Anderson, P, Buonanno, M, Epsley, C, Evans, B, Frolova, M, Goetsch, M, Hessinger, D, Ikehara, E, Ivanac, K, Kizko, J, Le, K, McNally-Dufort, C, Morocco, T, Nadkarni, S, Nissen, T, Nye, R, Pak, R, Pence, D, Redifer, P, Schwartz, W, Sattler, C, Schade, R, Sullivan, B, Wegner, J, Alvarez, Ca, Budassi, N, Vogel, Dr, Avaca, H, Conde, Dg, Estol, Cc, Gelersztein, E, Glenny, Ja, Hershson, Ar, Bruno, Rl, Maffei, Le, Soler, Jm, Zaidman, Cj, Carnero, Gs, Colombo, Hr, Jure, Ho, Luquez, Ha, Ramos, Hr, Resk, Jh, Rusculleda, Mm, Ulla, Mr, Caccavo, A, Farias, Ef, Wenetz, Lm, Cabella, Pr, Cuadrado, Ja, Chahin, M, Mackinnon, Ij, Zarandon, Rb, Schmidberg, J, Fernandez, Aa, Montana, O, Codutti, Or, Gorosito, Vm, Maldonado, N, Sala, J, De La Fuente RA, Casabella, Te, Di Gennaro JP, Guerrero, Ra, Alvarez, Ms, Berli, M, Botta, Ce, Montenegro, Ee, Vico, Ml, Begg, A, Lehman, R, Gilfillan, Cp, D'Emden, M, Markovic, Tp, Sullivan, D, Aroney, C, Stranks, Sn, Crimmins, Ds, Arstall, M, Van Gaal, W, Davis, T, Aylward, Pe, Amerena, J, William, M, Proietto, J, Purnell, Pw, Singh, B, Arya, Kw, Dart, Am, Thompson, P, Davis, Sm, Carroll, Pa, De Looze, F, Jayasinghe, R, Bhindi, R, Buysschaert, I, Sarens, T, van de Borne, P, Scott, Bp, Roosen, J, Cools, F, Missault, Lh, Debroye, C, Schoors, Df, Hollanders, G, Schroe, Hh, De Sutter, J, Hermans, K, Carlier, M, van Landegem, P, Verwerft, J, Mulleners, T, Delforge, Md, Soufflet, V, Elegeert, I, Descamps, Os, Janssens, S, Lemmens, Rc, Desfontaines, P, Scheen, A, Heijmans, S, Capiau, L, Vervoort, G, Carlier, Sg, Faes, D, Alzand, B, Keuleers, S, De Wolf, L, Thoeng, J, De Bruyne, L, de Santos MO, Felicio, Js, Areas, Ca, Figueiredo, El, Michalaros, Yl, Neuenschwander, Fc, Reis, G, Saad, Ja, Kormann, Ap, Nascimento, Cv, Precoma, Db, Abib, E Jr, dos Santos FR, Mello, Yg, Saraiva, Jf, Rech, Rl, Cerci, R, Fortes, Ja, Rossi, Pr, de Lima, e Silva FA, Hissa, M, Silva, Rp, de Souza WK, Guimarães Filho FV, Mangili, Oc, de Oliveira Paiva MS, Tumelero, R, Abrantes, Ja, Caramori, Pr, Dutra, Op, Leaes, Pe, Manenti, Er, Polanczyk, Ca, Bandeira, e Farias FA, de Moraes Junior JB, Russo, La, Alves AR Jr, Dracoulakis, Md, Ritt, Le, Saporito, Wf, Herdy, Ah, Maia, Ln, Sternieri, Mv, Ayoub, Jc, Bianco, Ht, da Costa FA, Eliaschewitz, Fg, Fonseca, Fa, Nakandakare, Er, Bonansea, Tc, Castro, Nm, de Barros, e Silva PG, Smith, P, Botelho, Rv, Resende, Es, Barbieri, Ds, Hernandes, Me, Bajaj, H, Beaudry, P, Berlingieri, Jc, Salter, Tj, Ajala, B, Anderson, Tj, Nanji, A, Ross, S, Pandey, S, Desrosiers, D, Gaudet, D, Moran, G, Csanadi, Ma, St-Amour, E, Cusimano, S, Halperin, Fa, Babapulle, M, Vizel, S, Petrella, J, Spence, Jd, Gupta, N, Tellier, G, Bourgeois, R, Gregóire, Jc, Wesson, T, Zadra, R, Twum-Barima, Dy, Cha, Jy, Hartleib, Mc, Bergeron, J, Chouinard, G, Mcpherson, Tp, Searles, G, Peterson, Sr, Mukherjee, A, Lepage, S, Conway, Jr, Kouz, Sm, Dion, D, Pesant, Y, Cheung, Ss, Goldenberg, Rm, Aronson, R, Gupta, Ak, O’Mahoney, M, Pliamm, L, Teitelbaum, I, Hoag, Gn, Nadra, Ij, Yared, Z, Yao, Lc, Nguyen, T, Saunders, Kk, Potthoff, S, Varleta, P, Assef, V, Godoy, Jg, Olivares, C, Roman, O, Vejar, M, Montecinos, H, Pincetti, C, Li, Y, Wang, D, Li, J, Yang, X, Du, Y, Wang, G, Yang, P, Zhang, X, Xu, P, Zhao, Y, Chen, J, Li, S, Li, W, Zhang, L, Zhu, Y, Zhang, Y, Zhou, C, Wang, Y, Liu, F, Ma, Y, Ti, Z, Zeng, X, Zhou, Y, Cui, G, Li, D, Xue, L, Jiang, J, Lian, Y, He, Y, Mendoza, Ja, Bonfanti, Ja, Dada, Fa, Urina-Triana, Ma, Rodriguez, Wr, Sanchez, Ml, Lozno, Hy, Triana, Eh, Arambula, Rm, Rico-Carrillo, Ae, Gallo, Hj, Catano, Js, Jattin, Fg, Plazas, Ja, Gomez, Je, Botero-Lopez, R, Gomez, Ni, Munoz, Cf, Pelaez, Sv, Eraso, Am, Goyes, Ar, Elbl, L, Fiserova, N, Vesely, J, Wasserburger, B, Blaha, V, Vojacek, J, Maskova, P, Hutyra, M, Vrkoc, J, Hala, T, Vodnansky, P, Bocek, P, Cifkova, R, Bufka, V, Ceska, R, Machkova, M, Zidkova, E, Lukac, M, Mikusova, T, Kellnerova, I, Kuchar, L, Ferkl, R, Cech, V, Zemek, S, Monhart, Z, Davidsen, F, Joensen, A, Lihn, As, Rasmussen, Tk, Wiggers, H, Lindgren, Lm, Schmidt, U, Galatius, S, Sillesen, H, Bronnum Schou, J, Thomsen, Kk, Urhammer, S, Jeppensen, J, Schou, M, May, O, Steffensen, R, Nielsen, Wb, Nielesen, T, Jepsen, Jm, Rai, A, Sykulski, R, Andersen, Lt, Rickers, H, Frost, L, Lomholdt, J, Egstrup, K, Wermuth, S, Klausen, L, Lassus, J, Palomaki, A, Khari, J, Tatlisumak, T, Kekki, S, Vanttinen, E, Strandberg, A, Valtonen, M, Sia, Sm, Nerg, O, Puhakka, M, Strand, J, Timonen, M, Levola, J, Arstila, L, Taurio, J, Kantola, I, Suomi, J, Humaloja, K, Askonen, K, Schiele, F, Sibon, I, Zemour, G, Goube, P, Petit, C, Chati, Z, Range, G, Rabahi, F, Rihani, R, Bergerot, C, Roubille, F, Boye, A, Probst, V, Ferrari, E, Cayla, G, Thouvenot, E, Delarche, N, Couffinhal, T, Coisne, D, Paillard, F, Elbaz, M, Decoulx, E, Angoulvant, D, Agraou, B, Caudmont, S, Berrouschot, J, Lauer, B, Schoell, I, Trenk, D, Derwahl, Km, Khariouzov, A, Proepper, F, Stawowy, P, Da Stephan, U, Stoessel, J, Voehringer, Hf, Dorsel, T, Stellbrink, C, Rinke, A, Northroff, J, Bourhaial, H, Stratmann, M, Wetzel, T, Axthelm, C, Guenzel, A, Weigmann, I, Faghih, M, Hagemann, D, Schaefer, A, Weber, D, Luedemann, J, Contzen, C, Kornmann, Mo, Winkelmann, B, Simon, J, Felix, S, Brauer, C, Laufs, U, Schmidt, E, Marten, I, Licka, M, Heisters, J, Appel, Kf, Kleinecke-Pohl, U, Klein, C, von Hodenberg EF, Maus, O, Sigal, H, Taeschner, H, Schwimmbeck, P, Lemke, B, Perings, C, Illies, G, Pfuetzner, A, Salbach, P, Hengstenberg, C, Kohler, A, Mudra, H, Behnke, T, Baar, M, Jeserich, M, Scholz, G, Naudts, I, Voller, H, Herrmann, Hj, von Engelhardt CB, Gerke, S, Pohlmeier, L, Schaufele, T, Woehrle, J, Al-Zoebi, A, Horacek, T, Peterfai, E, Kemeny, V, Lakatos, F, Bod, E, Andrassy, P, Andreka, P, Balo, T, Davidovits, Z, Laszlo, Z, Nagy, K, Papp, A, Somogyi, A, Toldy-Schedel, E, Vertes, A, Voros, P, Paragh, G, Martyin, T, Hajdu, C, Deak, L, Farago, K, Nagy, A, Kirschner, R, Koszegi, Z, Zilahi, Z, Toth, K, Wittmann, I, Bajcsi, D, Reiber, I, Toth, L, Benczur, B, Nagy, L, Sydo, T, Lupkovics, G, Oroszlan, T, Crean, P, Mahon, Ng, Mcadam, B, Macneill, B, Katz, A, Tsalihin, D, Vazan, A, Eitan, A, Lewis, Bs, Gavish, D, Wainstein, J, Mosenzon, O, Mosseri, M, Vishlitzky, V, Atar, S, Nseir, Wb, Brenner, H, Elis, A, Fuchs, S, Shimon, I, Solodky, A, Goldhaber, A, Tanne, D, Knobler, H, Kracoff, Oh, Hussein, O, Auriel, E, Chorin, E, Sharir, T, Bitzur, R, Shechter, M, Antonicelli, R, Franceschini, E, Porcu, M, Sesti, G, Maggiolini, S, Salvioni, A, Filardi, Pp, Trimarco, B, Averna, M, Pasqualini, L, Pirro, M, Pantaleoni, M, Piovaccari, G, Arca, M, Fedele, Francesco, Roncon, L, Anselmi, M, Sganzerla, P, Morocutti, G, Bonora, E, Dimas, Al, Esperon, Ga, Morales-Villegas, E, Isunza, Jm, Beltran, Lg, Molina, Ca, Garcia, Dk, Ruiz, La, Reyna, Ls, De los Rios Ibarra MO, Soto, Jr, Gonzalez-Ortiz, M, Herrera-Marmolejo, M, Ramos, Sa, Ramos-Lopez, Ga, Stobschinski, Ca, Aguilarsalinas, Ca, Alpizar-Salazar, M, Jimenez-Sanchez, M, Sanchez Mijangos JH, Elizondo Moreno ER, Garcia Castillo, A, Garcia Hernandez PA, Gonzalez-Gonzalez, Jg, Riojas Charles CM, Valdez Lopez HG, Nuriulu Escobar PL, Lechuga Martin del Campo, A, Castro Montes BE, Mendez Bucio, A, Rodriguez-Briones, I, Torre Amione, G, Violante Ortiz, R, Luna Ceballos RI, Lopez Rosas, E, Bax, Wa, Alhakim, M, van de Wiel, A, Liem, Ss, Groutars, Rg, Herrman, Jp, Hovingh, Gk, van de Wetering ML, van Royen, N, Groenemeijer, Be, Hoedemaker, G, Schaap, J, Ronner, E, Angun, M, Mairuhu, At, Van Alem AP, Martens, Fm, Heijmeriks, Ja, van Hal JM, Schoofs, Mw, den Hartog FR, Kentgens, S, Post, Jc, Louwerenburg, Jw, van Rossum, P, Viergever, Ep, Donders, Sh, Kamphuisen, Pw, van Beek, E, Nijmeijer, R, Lenderink, T, Schreuder, T, Kuijper, Af, The, Sh, Van het Hof-Wiersma JJ, Tichelaar, P, Westerndorp, I, Breedveld, Rw, Karalis, I, Romer, Tj, Bogaard, K, Van Koningsbruggen, P, Kroon, Aa, Hoogslag, Pa, Rensing, Bj, Cramer, E, Remmen, Jj, Riksen, Np, Bokern, Mj, Cabezas, Mc, Mulder, H, Nierop, Pr, van Kempen WW, Zoet-Nugteren, Sk, van Daele ME, Swart, Hp, van der Zwaan CT, Hermans, Wr, Magro, M, van de Wal RM, Hassink, Rj, Visseren, F, Veenendaal, A, De Nooijer, C, Troquay, Rp, Imholz, Bp, van der Meer, P, Visser, Rp, van Leendert RJ, Gosselink, Ma, Baker, J, Benatar, Jr, Kerr, J, Pryke, Jr, Scott, Rs, Millar-Corte, Gd, Williams, M, Montgomery, B, Venter, Dj, Ternouth, If, Decaigney, Sc, Hart, Hh, Corin, A, Garden, Pi, Sheahan, D, Harding, Sa, Korecki, J, Supronik, J, Styczkiewicz, M, Bijata-Bronisz, R, Rusicka, T, Walczak, M, Krolikowski, Z, Ostrowski, J, Lukaszewicz, M, Przekwas-Jaruchowska, M, Zieba, B, Miekus, P, Orkwiszewska-Nalewajko, A, Piepiorka, M, Kubalski, P, Wychota, K, Blach, E, Ochala, A, Okopien, B, Wronska, D, Janion, M, Czarnecka, D, Kolodziejczyk, J, Konieczynska, M, Landa, K, Mirek-Bryniarska, E, Necki, M, Pasternak, Da, Rozpondek, P, Trebacz, J, Walczewska, J, Sidor, M, Broncel, M, Drozdz, J, Kosmider, M, Saryusz-Wolska, M, Kucharska, D, Opalinska, E, Pijanowski, Z, Wozniak, I, Banaszkiewicz, K, Klecha, A, Horodecki, M, Piskorz-Wapinska, J, Kobielusz-Gembala, I, Kim, Mh, Kim, Dk, Cho, Br, Kim, Ks, Her, Sh, Lee, Sy, Rhee, My, Kim, K, Kang, Wc, Kim, Dh, Cho, Ys, Kim, Sh, Rim, Sj, Tahk, Sj, Jeon, Hk, Yoon, J, Mociran, M, Pop, Cf, Minescu, B, Andrei, Ld, Radoi, M, Calin, A, Ciomag, Rm, Copaci, I, Fruntelata, Ag, Popescu, M, Tivadar, S, Roman, G, Avram, Ri, Mistodie, Cv, Morosanu, M, Popa, Ar, Popescu, Ml, Popoviciu, Ms, Tase, A, Busegeanu, M, Popescu, A, Szilagyi, I, Sitterli-Natea, Cn, Maximov, Dm, Munteanu, M, Negrisanu, Gd, Kuzin, A, Popov, D, Shapovalova, J, Vishneva, E, Shutemova, E, Pasechnik, E, Bogdanov, E, Khasanov, N, Barbarash, Ol, Shangina, Oa, Tarasov, N, Solonev, O, Kosmacheva, E, Chernyatina, Ma, Ginzburg, M, Blokhin, A, Bulanova, N, Drapkina, Om, Gordeev, Ig, Libov, Ia, Lomakin, N, Panchenko, E, Shogenov, Zs, Zateyshchikov, D, Klein, G, Motylev, I, Belenkiy, Di, Demin, A, Nikolaev, Ky, Oleynikov, V, Zrazhevskiy, K, Katelnitskiy, I, Khaisheva, L, Aksentiev, S, Nedoshivin, A, Popova, Vb, Agafina, As, Ballyuzek, M, Baranova, E, Burova, N, Eryshev, S, Filippov, A, Goloshchekin, Bm, Konstantinov, V, Kostenko, Va, Simanenkov, Vi, Volkova, A, Duplyakov, D, Reshetko, O, Shvarts, Y, Kuznetsov, Va, Samoylova, Yg, Tolkacheva, V, Shalaev, Sv, Khokhlov, Al, Malygin, A, Shilkina, Np, Yakusevich, Vv, Margoczy, R, Zubek, V, Dzupina, A, Dubrava, J, Dulkova, K, Fabryova, L, Gaspar, L, Kamensky, G, Kokles, M, Raslova, K, Soosova, I, Stevlik, J, Strbova, J, Sumbal, J, Uhliar, R, Micik, J, Truban, J, Fedacko, J, Pastrnakova, E, Pella, D, Fazekas, F, Ambrovicova, V, Kycina, P, Martinka, E, Nociar, J, Belicova, M, Banik, M, Kanderkova, D, Hranai, M, Duris, T, Krahulec, B, Benacka, J, Vinanska, D, Roskova, E, Skripova, D, Macek, V, Vohnout, B, Buganova, I, Engelbrecht, Jm, Pretorius, Mm, Ebrahim, Io, Bayat, J, Ganesh, S, Ranjith, N, Coetzer, Tf, Jacovides, A, Distiller, La, Hellig, Fs, Engelbrecht, Iv, Mahomed, Aa, Blignault, Sc, Burgess, Lj, Kotze, Hj, van Nieuwenhuizen, E, Musungaie, Db, Emanuel, S, van der Walt, E, Pretorius, Ce, Roos, Js, Roux, Sm, Badat, Ae, Fouche, L, Vahed, Ya, Jansen van Resburg, D, van Zyl LJ, Soto Gonzalez, A, Diaz, Jl, Segura, T, Botella Serrano, M, Botas Rodrigues, J, Molto-Jorda, Jm, Dominguez Escribano JR, Sogorb Garri, F, Blanco Coronado JL, Gaztambide Saenz MS, Brotons Cuixart, C, Bruguera Cortada, J, Garcia-Moll Marimon, X, Gonzalbez Morgaez JD, Maisterra Santos, O, Roquer Gonzalez, J, Sobrino-Martinez, J, Chueca Fernandez JE, Narejos, S, Suarez Garcia, S, Perez Martinez, P, Figueras Camos, R, Medrano Martinez, V, Bellido Guerrero, D, Martinez Deben, F, Vila Belmonte, A, Mediavilla Garcia JD, Romero Hinojosa JA, Martorell Mateu, E, Cequier Fillat AR, Pinto Sala, X, Adroer Martori, R, Bueno Diez, M, Lopez Cano, C, Worner Diz, F, Gonzalez Juanatey, C, Alvarez-Sala Walther LA, De Dios Garcia Diaz, J, Garcia Puig, J, Jodar Gimeno, E, Plaza Perez, I, Suarez-Fernandez, C, Tunon, J, Zamorano Gomez JL, Brito Sanfiel MA, Escudier Villa JM, de Mora Martin, M, Dominguez Lopez, M, Hernandez Garcia JM, Tinahones Madueno FJ, Perez Paredes, M, Aracil Villar, J, Barreda Gonzalez MJ, Ripoll Vera TV, Tofe Povedano, S, Sanchez Alvarez, J, Martinez Via, L, Robles Iniesta, A, Masana, L, Vinyoles Bargallo, E, Calvo Gomez, C, Gonzalez Juanatey JR, Cruz Fernandez JM, De La Cuesta Mayor, C, Duran Garcia, S, Jimenez Hernandez MD, Morales Portillo, C, Muniz Grijalvo, O, De Castro, R, Taverna Llaurado, E, Pons Amate JM, Terns Riera, M, Civeira Murillo, F, Linderfalk, C, Curiac, D, Saldeen-Nilehn, K, Koskinen, P, Khalili, P, Tortensson, I, Lindholm, Cj, Luts, A, Koskinen, Pt, Gottsater, A, Persson, Be, Mooe, T, Larnefeldt, H, Boman, K, Crisby, M, Rasmanis, G, Tengmark, Bo, Witt, N, Hagstrom, E, Viklund, J, Muller, C, Mach, F, Burnier, M, Nanchen, D, Wuerzner, G, Banyai, M, Moccetti, T, Miserez, Ar, Bilz, S, Weber, K, Lai, Wt, Chang, Kc, Ueng, Kc, Tsai, Wc, Chiang, Ce, Hou, C, Pei, D, Krittayaphong, R, Kiatchoosakun, S, Srimahachota, S, Boonyavarakul, A, Jintapakorn, W, Gullu, H, Onrat, E, Erkan, Af, Demirci, D, Sari, R, Ceyhan, C, Ari, H, Araz, M, Degertekin, M, Goktekin, O, Uresin, Ay, Yigit, Z, Akdeniz, B, Comlekci, A, Kayikcioglu, M, Sahin, T, Ozcan, T, Durakoglugil, E, Asamoah-Owusu, N, Reed, R, Bakhai, A, Dixon, L, Sharma, R, Avornyo, Aa, Jones, Af, Lip, G, Clark, R, Banerjee, M, Wakeling, J, Arden, C, Blagden, Md, Walukiewica, P, Marshall, A, Maxwell, Tg, Gunstone, Ae, Kadr, Hh, Patle, R, Arif, I, Jhund, Ps, Mckaig, G, Douglas, F, Mierzejewski, L, Turner, W, Sathyapalan, T, Ivan, P, Manoj, A, Rice, S, Collier, Dj, Nair, Dr, Thom, S, Fiore, G, De Belder, M, Price, D, Sobolewska, J, Martin, S, Takhar, A, Moriarty, A, Kondagunta, V, Myhill, T, Gibson, Jm, Cecil, Jt, Halcox, J, Annamalai, N, Gorog, Da, Mccormack, T, Pegge, N, Field, A, Adams, F, Klein, Jj, Busch, Rs, Bretton, Em, Jaffrani, N, Salacata, A, Assadourian, A, Gogia, Hs, Dyke, Ck, Rubenfire, M, Essandoh, Lk, Welker, Ja, Ledesma, G, Lupovitch, S, Delgado, Jp, Hendrix, El, Quyyumi, Aa, Riesenberg, Ra, Robertson, Dg, Weinstein, Dl, Weiss, R, Casaubon, L, Gammon, Rs, Brar, Hs, Bittar, Gd, Guarnieri, Tt, Ince CS Jr, Jrquraishi, Am, Saeed, S, Albert, M, Sotolongo, Rp, Bernard, Jv, Karlsbergg, Rp, Lepor, Ne, Kirby, We, Mclean, B, Miller, Ap, Ovalle, F, Townsend, Jc, Beckett, Pl, Eaves, Wb, West, Sh, Kosinski, Ej, Zarich, Sw, Mahal, Ss, Maw, K, Maynard, Km, Chen, Jc, Gelormini, J, Gottlieb, Dw, Gabra, Nw, Narayan, P, Sparks, J, Field, Jc, Willits, Vl, O’Steen, Mb, Pasquini, Ja, Sensebrenner, Jw, Yarows, Sa, Hiotis, L, Jagielo, Tj, Levinson, Dj, Diller, Pm, Kereiakes, Dj, Turner, Ta, Vincent, S, Camp, Ad, Denker, Ps, Manning, Mb, Rocco, Mb, Stamps, Hb, Strader, Jr, Uusinarkaus, Kt, Kennett, Jd, Leichter, Sb, Mcneil, Dl, Schumacher, Dr, Chang, Ar, Ellison, Hs, Updegrove, Jd, Hamroff, Gs, Kay, Js, Marar, Ie, Flores, E, Saini, S, Abdullah, S, Berk, Mr, Fordan, S, Joshi, Ph, Mccullough, Pa, Reynolds, Rd, Rosenstock, J, Sachson, Ra, Shammas, N, Fishbein, Gj, Randall, Wj, Henderson, Da, Nash, Ml, Barker, Ba, Cohen, Ss, Seidman, B, Odekirk, Ll, Grillo, Rs, Martinez, Lm, Multani, P, Alwine, Lk, Mcgarvey, Jf, Mollerus, Me, Miller, Ab, Kotek, Lw, Changlani, M, Zavaro, Sh, Munoz, F, Mehta, Pm, Helm, Rj, Farhat, Nz, Farsad, R, Raoof, Tj, Shultz, Jh, Geohas, Jg, Allaw, Ma, Dela Llana, A, Gutmann, Je, Inzerello, At, Alappat, P, George, Ar, Haddad, Tm, Lillestol, Mj, Grodman, R, Peniston, Jh, Wadud, K, Garcia, B, Hamilton, Me, Lerman, S, Perloff, De, Graff, A, Saxena, S, Alvarado, Op, Malik, A, Reddy, Rd, Kinzfogl, G, Cornett, Gm, Norwood, Pc, Gilbert, Jm, Willis, Jg, Mcgrew, F, Sharma, S, Castro, Ma, Cucher, Fh, Altafullah, Im, Khurana, S, Knutson, Tj, Kinnaman, Sj, Stuckey, T, Pudi, Kk, Mayfield, Rk, Funk, Gs, Nixon, Wa, Dor, I, Boyett, Be, Srivastava, S, Elosegui, Am, Isserman, Sm, Cheek, Hb, Promisloff, Sd, Tami, Lf, Zeig, S, fitz-Patrick, D, Dave, Kn, Ahmad, A, Arain, S, Ballantyne, Cm, Doshi, A, El Hafi SE, Feldman, J, Fragoso, Vg, Gilford, T, Hoffman, As, Pouzar, Je, Vivekananthan, K, Ansari, Sh, Strzinek, Ra, Crater, Ta, Robinson, Jg, Fulmer, Jj, Patel, Am, Pereira, Es, Stich, Ma, Sultan, S, Geskin, G, Ruoff, Ge, Gillespie, E, Bybee, Ka, Moriarty, Pm, Savin, V, Agaiby, Jm, Melucci, Mb, Jantzi, Cm, Davidson, E, Smith, Wb, Treasure, Cb, Wakefield, Ph, Deck, K, Edris, Ma, Gilmore, Rm, Seep, Mk, Andersen, Jl, Detweiler, Ro, Rosenfeld, Jc, Strobl, Dj, Steinhoff, Jp, Adams, A, Estevez, R, Molin, Cj, Kim, Cy, Dy, J, Fox, Ke, Farris, Nr, Wayne, Jd, Whitney, Rt, Randhawa, Pm, Mego, Dm, Macdolnald, L, Caputo, Rp, Rigolosi, R, Vannatta, B, Pacheco, Tr, El-Shahawy, M, Gonzalez, Ej, Guice, Mj, Cherlin, Rs, Bays, He, Shoukfeh, M, Morris, Fh, Loy, J, Vora, Sk, Staab, Pk, Frisoli, A, Kimmel, Ma, Cohen, Aj, Green, Cb, Whitlock, L, Butuk, Dj, Mccartney, Mj, Ables, Lr, Acosta, R, Alvarez, Jg, Barrera, Cm, Benitez, O, Berenguer, Ra, Breton, Cf, Chiong, R, Delgado, Mi, Dufreny, A, Fialkow, Ja, Franczek, S, Frias, Jj, Iglesias, C, Landron-Garcia, L, Llerena, Sn, Martinez, Rf, Miranda, Aa, Morytko, Ja, Rodriguez, Ij, Sotolongo, R, Suarez-Sarmiento, A, Terrelonge, Ae, Vaca, Ce, Venereo, Jm, Verdeza, C, Zeno, Ml, Chilka, S, Felten, Wr, Hartman, An, Shayani, Ss, Duprez, D, Knickelbine, T, Chambers, Jd, Cone, Cl, Broughton, R, Napoli, Mc, Seaton, Bl, Smith, Sk, Reedy, Ma, Kesani, Mk, Nicol, Pr, Stringam, So, Talano, Jv, Barnum, O, Desai, V, Montero, M, Jacks, Rk, Kostis, Jb, Owen, Jg, Makam, Sk, Grosman, I, Underberg, Ja, Masri, Be, Peters, Ss, Serje, J, Lenhard, Mj, Glover, R, Paraboschi, Cf, Lim, Eh, Connery, L, Kipgen, W, Bravo, P, Digiovanna, Mj, Tayoum, H, Gabriel, Jd, Ariani, Mk, Robinson, Mf, Clemens, Pc, Corder, Cn, Schifferdecker, B, Tahirkheli, Nk, Hurling, Rt, Rendell, Ms, Shivaswamy, V, Madu, Ij, Dahl, Cf, Ayesu, K, Kim, C, Barettella, Mb, Jamidar, Ha, Bloom, Sa, Vora, Kn, Ong, St, Aggarwala, G, Sack, G, Blaze, K, Krichmar, P, Murcia, A, Teltser, M, Villaman-Bencosme, Y, Fahdi, Ie, Williams, Dg, Lain, El, Garcia, Hl, Karim, Sn, Francyk, Dm, Gordon, Mb, Palchick, Ba, Mckenzie, Me, Gimness, Mp, Greiff, J, Ruiz-R, L, Vazquez-Tanus, Jb, Schlager, D, Connelly, T, Soroka, E, Hastings, Wl, O’Dea, Dj, Purdy, Da, Jackson, B, Arcanese, Ml, Strain, Je, Schmedtje JF Jr, Jrdavis, Mg, A, A, Prasada, S, Scott, Dl, Vukotic, G, Akhtar, N, Larsen, Dc, Rhudy, Jm, Zebrack, Js, Bailey, Sr, Grant, Dc, Mora, A, Perez, Ja, Reyes, Rg, Sutton, Jc, Brandon, Dm, First, Bp, Risser, Ja, Claudio, J, Figueroa-Cruz, Wl, Sosa-Padilla, Ma, Tan, Ae, Traboulssi, Ma, Morcos, Nc, Glaser, La, Bredlau, Ce, El Shahawy, M, Ramos, Mj, Kandath, Dd, Kaluski, E, Akright, L, Rictor, Kw, Pluto, Tm, Hermany, Pr, Bellingar, B, Clark, Gb, Herrod, Jn, Goisse, M, Hook, M, Barrington, P, Lentz, Jd, Singal, Dk, Gleason, Gp, Lipetz, Rs, Schuchard, Tn, Bonner, Jh, Forgosh, Lb, Lefebvre, Gc, Pierpoint, Be, Radin, Dm, Stoller, Sr, Segall, N, Shah, Sa, Ramstad, Ds, Nisnisan, Jm, Trippett, Jm, Benjamin, Sa, Labissiere, Jc, Nashed, An, Maaieh, M, Aslam, Aa, Mandviwala, M, Budoff, Mj, French, Wj, Vlach, Jj, Destefano, P, Bayron, Cj, Fraser, Nj, Sandberg, Jh, Fagan, Tc, Peart, Bc, Suryanarayana, Pg, Gupta, Dk, Lee, Mw, Bertolet, Bd, Hartley, Pa, Kelberman, M, Behmanesh, B, Buynak, Rj, Chochinov, Rh, Steinberg, Aa, Chandna, H, Bjasker, Kr, Perlman, Rl, Ball, Em, Pock, J, Singh, S, Baldari, D, Kaster, S, Lovell, Jp, Horowitz, Bs, Gorman, Ta, Pham, Dn, Landzberg, Js, Mootoo, Ki, Moon, E, Krawczyk, J, Alfieri, Ad, Janik, Mj, Herrington, Dm, Koilpillai, Rn, Waxler, Ar, Hoffman, Da, Sahul, Zh, Gumbiner, B, Cropp, A, Fujita, K, Garzone, P, Imai, K, Levisetti, M, Plowchalk, D, Sasson, S, Skaggs, J, Sweeney, K, Vincent, J., Curto, M, Ridker, P., Revkin, J., Amarenco, P., Brunell, R., Curto, M., Civeira, F., Flather, M., Glynn, R., Gregoire, J., Jukema, J., Karpov, Y., Kastelein, J., Koenig, W., Lorenzatti, A., Manga, P., Masiukiewicz, U., Miller, M., Mosterd, A., Murin, J., Nicolau, J., Nissen, S., Ponikowski, P., Santos, R., Schwartz, P., Soran, H., White, H., Wright, R., Vrablik, M., Yunis, C., Shear, C., Tardif, J., SPIRE Cardiovascular Outcome Investigators, Averna, M., Brigham and Women's Hospital [Boston], Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), RS: CARIM - R3.02 - Hypertension and target organ damage, MUMC+: MA Alg Interne Geneeskunde (9), Interne Geneeskunde, Ridker, P. M., Glynn, R. J., Jukema, J. W., Kastelein, J. J. P., Nicolau, J. C., Santos, R. D., Schwartz, P. F., Wright, R. S., Shear, C. L., Tardif, J. -C., SPIRE Cardiovascular Outcome Investigator, Perrone, Filardi, P, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
Subjects: Male, STATIN THERAPY, Anticholesteremic Agents/adverse effects, Antibodie, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Injections, Subcutaneous/adverse effects, 030204 cardiovascular system & hematology, Bococizumab, law.invention, PCSK9, 0302 clinical medicine, Randomized controlled trial, law, Risk Factors, GENETIC-VARIANTS, Cardiovascular Disease, Monoclonal, Anticholesteremic Agent, 030212 general & internal medicine, Myocardial infarction, Treatment Failure, Humanized, Proprotein Convertase 9/antagonists & inhibitors, Medicine(all), Antibodies, Antibodies, Monoclonal, Humanized, Anticholesteremic Agents, Cardiovascular Diseases, Cholesterol, LDL, Double-Blind Method, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Injections, Subcutaneous, Lipids, Middle Aged, Proprotein Convertase 9, Medicine (all), PCSK9 Inhibitors, antibodies monoclonal humanized, anticholesteremic agents, cardiovascular diseases, cholesterol, LDL, double-blind method, female, follow-up studies, humans, hypercholesterolemia, injections, subcutaneous, lipids, male, middle aged, proprotein convertase 9, risk factors, treatment failure, medicine (all), Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], General Medicine, Lipid, 3. Good health, LDL/blood, Multicenter Study, Cholesterol, TRIALS, Cholesterol, LDL/blood, Antibodies, Monoclonal, Humanized/adverse effects, Randomized Controlled Trial, subcutaneous, lipids (amino acids, peptides, and proteins), Cardiovascular Diseases/prevention & control, REDUCING LIPIDS, Human, medicine.medical_specialty, animal structures, Hypercholesterolemia/drug therapy, Placebo, Injections, Subcutaneou, LDL, Injections, Follow-Up Studie, EVENTS, 03 medical and health sciences, Internal medicine, medicine, Journal Article, Comparative Study, METAANALYSIS, Alirocumab, business.industry, Unstable angina, Lipids/blood, Risk Factor, fungi, Antibodies/blood, ta3121, medicine.disease, Surgery, Evolocumab, REDUCTION, Humanized/adverse effects, Subcutaneous/adverse effects, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Item does not contain fulltext BACKGROUND: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS: At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P/=70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P=0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of >/=100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P=0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P
Published: 2017

7. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study

Author: Barbin, L. (Laetitia), Rousseau, C. (Chloe), Jousset, N. (Natacha), Casey, R. (Romain), Debouverie, M. (Marc), Vukusic, S. (Sandra), De Seze, J. (Jerome), Brassat, D. (David), Wiertlewski, S. (Sandrine), Brochet, B. (Bruno), Pelletier, J. (Jean), Vermersch, P. (Patrick), Edan, G. (Gilles), Lebrun-Frenay, C. (Christine), Clavelou, P. (Pierre), Thouvenot, E. (Eric), Camdessanché, J. (Jean-Philippe), Tourbah, A. (Ayman), Stankoff, B. (Bruno), Al Khedr, A. (Abdullatif), Cabre, P. (Philippe), Papeix, C. (Caroline), Berger, E. (Eric), Heinzlef, O. (Olivier), Debroucker, T. (Thomas), Moreau, T. (Thibault), Gout, O. (Olivier), Bourre, B. (Bertrand), Créange, A. (Alain), Labauge, P. (Pierre), Magy, L. (Laurent), Defer, G. (Gilles), Foucher, Y. (Yohann), Laplaud, D. (David A), CFSEP and OFSEP groups, Jonchère, Laurent, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Biostatistique, Pharmacoépidémiologie et Mesures Subjectives en Santé, PRES Université Nantes Angers Le Mans (UNAM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), ReLSEP, Lorraine Register of MS, EA 4360, Department of Neurology, CHU Nancy, Department of Neurology, CHU Lyon, Service de Neurologie [Lyon], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université de Bordeaux (UB), Pôle de Neurosciences Cliniques, Department of Neurology, Hôpital de la Timone [CHU - APHM] (TIMONE), Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Service de neurologie D, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Clermont-Ferrand, CHU Saint-Etienne, Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU de la Martinique [Fort de France], CHU Pitié-Salpêtrière [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neurologie [CHRU Besançon], Service de Neurologie [CHU de Poissy], CHU De Poissy, Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Fondation Ophtalmologique Rothschild, Excitabilité nerveuse et thérapeutique (ENT), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Télécom Bretagne-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Télécom Bretagne-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Université de Bretagne Sud (UBS)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-EA 4391, Service de Physiologie Explorations Fonctionnelles-Hôpital Henri Mondor, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), and Service de Neurologie [CHU Besançon]
Subjects: Male, [SDV]Life Sciences [q-bio], Aucun, diagnosis, drug therapy, epidemiology, Cohort Studies, 0302 clinical medicine, Natalizumab, Medicine, 030212 general & internal medicine, 10. No inequality, Fingolimod, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Cohort, Female, France, Immunosuppressive Agents, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Multiple Sclerosis, Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC], Article, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Fingolimod Hydrochloride, Internal medicine, Humans, Immunologic Factors, Expanded Disability Status Scale, business.industry, Multiple sclerosis, medicine.disease, Surgery, Propylene Glycols, therapeutic use, Propensity score matching, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: OBJECTIVE: To compare natalizumab and fingolimod on both clinical and MRI outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) from 27 multiple sclerosis centers participating in the French follow-up cohort Observatoire of Multiple Sclerosis. METHODS: Patients with RRMS included in the study were aged from 18 to 65 years with an Expanded Disability Status Scale score of 0-5.5 and an available brain MRI performed within the year before treatment initiation. The data were collected for 326 patients treated with natalizumab and 303 with fingolimod. The statistical analysis was performed using 2 different methods: logistic regression and propensity scores (inverse probability treatment weighting). RESULTS: The confounder-adjusted proportion of patients with at least one relapse within the first and second year of treatment was lower in natalizumab-treated patients compared to the fingolimod group (21.1% vs 30.4% at first year, p = 0.0092; and 30.9% vs 41.7% at second year, p = 0.0059) and supported the trend observed in nonadjusted analysis (21.2% vs 27.1% at 1 year, p = 0.0775). Such statistically significant associations were also observed for gadolinium (Gd)-enhancing lesions and new T2 lesions at both 1 year (Gd-enhancing lesions: 9.3% vs 29.8%, p < 0.0001; new T2 lesions: 10.6% vs 29.6%, p < 0.0001) and 2 years (Gd-enhancing lesions: 9.1% vs 22.1%, p = 0.0025; new T2 lesions: 16.9% vs 34.1%, p = 0.0010) post treatment initiation. CONCLUSION: Taken together, these results suggest the superiority of natalizumab over fingolimod to prevent relapses and new T2 and Gd-enhancing lesions at 1 and 2 years. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS, natalizumab decreases the proportion of patients with at least one relapse within the first year of treatment compared to fingolimod. comparative study journal article multicenter study observational study research support, non-u.s. gov't 2016 Feb 23 2016 01 29 imported
Published: 2016

8. The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

Author: Alexis Montcuquet, Henrik Kahr Mathiesen, Tomas Kalincik, Marc Girard, Karolina Hankiewicz, Marco Onofrj, Francois Grand Maison, Raed Alroughani, Mathilde Lefort, Olivier Gout, Jeannette Lechner-Scott, Marc Debouverie, Julie Prevost, Eva Havrdova, Olivier Casez, Per Soelberg Sørensen, Pierre Duquette, Jean Pelletier, Claudio Solaro, Alessandra Lugaresi, Francesco Patti, Emmanuelle Leray, Johanna Balslev Andersen, Bassem Yamout, Céline Labeyrie, Karen Schreiber, Eric Thouvenot, Nils Koch-Henriksen, Michael Broksgaard Jensen, Elisabeth Maillart, Chantal Nifle, Stephan Bramow, Pierre Clavelou, Bruno Stankoff, Olivier Heinzlef, Finn Sellebjerg, Abir Wahab, Mark Slee, Gilles Defer, Pierre Labauge, Melinda Magyari, Steve Vucic, Guillermo Izquierdo, Helmut Butzkueven, Peter Vestergaard Rasmussen, Bertrand Bourre, Maria Trojano, Franco Granella, Corinne Pottier, Jette L. Frederiksen, Olga Skibina, Recai Turkoglu, Ivania Patry, Pierre Grammond, Bart Van Wijmeersch, Eric Berger, Aurélie Ruet, Serkan Ozakbas, Jonathan Ciron, Tünde Csépány, Jean Philippe Camdessanche, Sandra Vukusic, Nicolas Maubeuge, David Laplaud, Cavit Boz, Christine Lebrun, Claudia C. Hilt Christensen, Patrizia Sola, Vahid Shaygannejad, Romain Casey, Murat Terzi, Philippe Cabre, Jérôme De Seze, Abdullatif Al-Khedr, Dana Horakova, Pamela A. McCombe, Daniele Spitaleri, Alexandre Prat, Gilles Edan, Hélène Zéphir, Aude Marousset, Sifat Sharmin, Diana Ferraro, Sara Eichau, Rana Karabudak, Thibault Moreau, Sellebjerg, Finn/0000-0002-1333-9623, Lugaresi, Alessandra/0000-0003-2902-5589, frederiksen, jette/0000-0003-1661-7438, Ciron, Jonathan/0000-0002-3386-6308, University of Copenhagen = Københavns Universitet (KU), University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Aarhus University Hospital, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The study was conducted separately and apart from the guidance of the sponsors. CORe received funding from NHMRC [1140766, 1129789, 1157717] to support studies of comparative effectiveness of MS therapies.OFSEP was supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation.DMSR did not receive any funding to collaborate in this study., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Andersen J.B., Sharmin S., Lefort M., Koch-Henriksen N., Sellebjerg F., Sorensen P.S., Hilt Christensen C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Eichau S., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Shaygannejad V., Prevost J., Skibina O., Solaro C., Karabudak R., Wijmeersch B.V., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., Seze J.D., Maillart E., Zephir H., Labauge P., Defer G., Lebrun C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Marousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Leray E., Laplaud D.A., Butzkueven H., Kalincik T., Vukusic S., Magyari M., University of Copenhagen = Københavns Universitet (UCPH), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], CHU Limoges, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Saint-Denis [Ile-de-France], Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Centre Hospitalier de Versailles André Mignot (CHV)
Subjects: medicine.medical_specialty, Fingolimod, Head-to-head comparison, Multiple sclerosis, Natalizumab, Treatment effectiveness, [SDV]Life Sciences [q-bio], Relapse rate, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, Fingolimod Hydrochloride, Epidemiology, Humans, Medicine, Multiple sclerosi, Registries, 030212 general & internal medicine, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, First relapse, Treatment Outcome, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform meth-odologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/ exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab-and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed. BiogenBiogen; NovartisNovartis; MerckMerck & Company; RocheRoche Holding; Teva; Sanofi GenzymeSanofi-AventisGenzyme Corporation; NHMRCNational Health and Medical Research Council of Australia [1140766,1129789, 1157717]; French State; Agence Nationale de la Recherche-French National Research Agency (ANR)European Commission [ANR-10-COHO-002]; Eugene Devic EDMUS Foundation; ARSEP Foundation
Published: 2021

9. Determinants of therapeutic lag in multiple sclerosis

Author: Tomas Kalincik, Marc Girard, Corinne Pottier, Murat Terzi, Jean Pelletier, Oliver Gerlach, Julie Prevost, Dana Horakova, Francois Grand'Maison, Raed Alroughani, Guillermo Izquierdo, Francesco Patti, Federico Frascoli, Maria Trojano, Franco Granella, Pamela A. McCombe, Charles B Malpas, Recai Turkoglu, Aurélie Ruet, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Helmut Butzkueven, Pierre Clavelou, Tamara Castillo Trivino, Marco Onofrj, Jean Philippe Camdessanche, Pierre Labauge, Vincent Van Pesch, Pierre Grammond, Abir Wahab, Roberto Bergamaschi, Aysun Soysal, Diana Ferraro, Bertrand Bourre, Olivier Gout, Jeannette Lechner-Scott, Sara Eichau, Emmanuelle Leray, Alexis Montcuquet, Pierre Duquette, Olivier Casez, Youssef Sidhom, Patrizia Sola, Bart Van Wijmeersch, Izanne Roos, Gilles Edan, Serkan Ozakbas, David Laplaud, Sandra Vukusic, Abdullatif Al Khedr, Céline Labeyrie, Philippe Cabre, Eric Thouvenot, Céline Louapre, Romain Casey, Alessandra Lugaresi, Riadh Gouider, Alasdair Coles, Eric Berger, Ivania Patry, Gerardo Iuliano, Elisabetta Cartechini, Cavit Boz, Karolina Hankiewicz, Eva Havrdova, Eduardo Aguera-Morales, J William L Brown, Jérôme De Seze, Bruno Stankoff, Olivier Heinzlef, Gilles Defer, Alexandre Prat, Chantal Nifle, Maria José Sá, Marc Debouverie, Daniele Spitaleri, Aude Maurousset, Thibault Moreau, Christine Lebrun-Frenay, Hélène Zéphir, University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), Swinburne University of Technology [Melbourne], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Charles University [Prague], Università degli studi di Catania [Catania], Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Università degli Studi di Modena e Reggio Emilia (UNIMORE), University of Queensland [Brisbane], Monash University [Clayton], UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Charles University [Prague] (CU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Hospital Virgen Macarena, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), CHU Toulouse [Toulouse], INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Fernando Pessoa University, Azienda Ospedaleria Universitaria di Modena, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Karadeniz Technical University (KTU), Università degli Studi di Macerata = University of Macerata (UNIMC), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), University of Newcastle [Australia] (UoN), Zuyderland Hospital [Heerlen, The Netherlands], Ondokuz Mayis University, University of Parma = Università degli studi di Parma [Parme, Italie], Amiri hospital, University of Salerno (UNISA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hasselt University (UHasselt), San Giuseppe Moscati Hospital [Avellino, Italie], Bakirkoy Matern & Childrens State Hosp, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Universidad de Córdoba [Cordoba], Hospital Donostia, CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHI Poissy-Saint-Germain, Université de la Manouba [Tunisie] (UMA), University of Debrecen, Hôpital Charles Nicolle [Rouen], CHU Amiens-Picardie, CHU de la Martinique [Fort de France], CHU Limoges, CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], This study was supported by the EDMUS Foundation and NHMRC [1140766,1129189, 1157717]. IR is supported by a MSIF-ARSEP McDonald fellowship grantand a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profitorganization that receives support from Biogen, Novartis, Merck, Roche, Teva andSanofi Genzyme. The study was conducted separately and apart from the guidanceof the sponsors. The Observatoire Français de la Sclérose en Plaques (OFSEP) issupported by a grant provided by the French State and handled by the 'AgenceNationale de la Recherche,' within the framework of the 'Investments for the Future'program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUSFoundation against multiple sclerosis and by the ARSEP Foundation., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Roos I., Leray E., Frascoli F., Casey R., Brown J.W.L., Horakova D., Havrdova E.K., Debouverie M., Trojano M., Patti F., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grammond P., Ciron J., Ruet A., Ozakbas S., De Seze J., Louapre C., Zephir H., Sa M.J., Sola P., Ferraro D., Labauge P., Defer G., Bergamaschi R., Lebrun-Frenay C., Boz C., Cartechini E., Moreau T., Laplaud D., Lechner-Scott J., Grand'Maison F., Gerlach O., Terzi M., Granella F., Alroughani R., Iuliano G., Van Pesch V., Van Wijmeersch B., Spitaleri D.L.A., Soysal A., Berger E., Prevost J., Aguera-Morales E., McCombe P., Castillo Trivino T., Clavelou P., Pelletier J., Turkoglu R., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Sidhom Y., Gouider R., Csepany T., Bourre B., Al Khedr A., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Coles A., Malpas C.B., Vukusic S., Butzkueven H., Kalincik T., Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli studi di Catania = University of Catania (Unict), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), University of Newcastle [Callaghan, Australia] (UoN), Ondokuz Mayis University (OMU), Università degli studi di Parma = University of Parma (UNIPR), Universidad de Córdoba = University of Córdoba [Córdoba], University of Debrecen Egyetem [Debrecen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Registrie, Male, medicine.medical_specialty, Treatment response, Pediatrics, Neurology, Lag, [SDV]Life Sciences [q-bio], Aucun, multiple sclerosis, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Recurrence, medicine, Humans, Treatment effect, Disabled Persons, Registries, 030304 developmental biology, 0303 health sciences, business.industry, Multiple sclerosis, Delayed onset, medicine.disease, 3. Good health, Clinical neurology, therapeutic lag, multiple sclerosi, Disease Progression, Disabled Person, Observational study, Female, observational study, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract: International audience; Objective: To explore the associations of patient and disease characteristics with the duration of therapeutic lag for relapses and disability progression.Background: Therapeutic lag represents the delay from initiation of therapy to attainment of full treatment effect. Understanding the determinants of therapeutic lag provides valuable information for personalised choice of therapy in multiple sclerosis (MS).Design/Methods: Data from MSBase, a multinational MS registry, and OFSEP, the French national registry, were used. Patients diagnosed with MS, minimum 1-year exposure to MS treatment, minimum 3-year pre-treatment follow up and yearly review were included in the analysis. By studying incidence of relapses and 6-month confirmed disability progression, the duration of therapeutic lag was calculated by identifying the first local minimum of the first derivative after treatment start in subgroups stratified by patient and disease characteristics. Pairwise analyses of univariate predictors were performed. Combinations of determinants that consistently drove differences in therapeutic lag in pair by pair analyses were included in the final model.Results: Baseline EDSS, ARR and sex were associated with duration of therapeutic lag on disability progression in univariate and pairwise bivariable analyses. In the final model, therapeutic lag was 27.8 weeks shorter in females with ARR6 compared to those with EDSS>=6 (26.6, 18.2–34.9 vs 54.3, 47.2–61.5). Baseline EDSS, ARR, sex and MS phenotype were associated with duration of therapeutic lag on relapses in univariate analyses. Pairwise bivariable analyses of the pairs of determinants suggested ependently associated with therapeutic lag. In the final model, therapeutic lag was shortest in those with RRMS and EDSS
Published: 2021

10. Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts

Author: Mark Slee, Guillermo Izquierdo, Per Soelberg Soerensen, Karen Schreiber, Alexandre Prat, Francois Grand'Maison, Maria Trojano, Franco Granella, Pierre Duquette, David Laplaud, Elisabeth Maillart, Henrik Kahr Mathiesen, Bassem Yamout, Cavit Boz, Jean Pelletier, Corinne Pottier, Jette L. Frederiksen, Claudia Christina Pfleger, Tomas Kalincik, Olivier Gout, Daniele Spitaleri, Marc Girard, Marco Onofrj, Jérôme De Seze, Helmut Butzkueven, Emmanuelle Leray, Philippe Cabre, Julie Prevost, Abullatif Al-Khedr, Aude Maurousset, Eric Berger, Sifat Sharmin, Ivania Patry, Pamela A. McCombe, Patrizia Sola, Olga Skibina, Diana Ferraro, Pierre Clavelou, Francesco Patti, Finn Sellebjerg, Niels Koch-Henriksen, Alexis Montcuquet, Recai Turkoglu, Romain Casey, Bart Van Wijmeersch, Hélène Zéphir, Pierre Grammond, Dana Horakova, Davide Maimone, Serkan Ozakbas, Céline Labeyrie, Murat Terzi, Aurélie Ruet, Steve Vucic, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Bruno Stankoff, Mathilde Lefort, Katherine Buzzard, Karolina Hankiewicz, Jean-Philippe Camdessanché, Raed Alroughani, Michael Broksgaard Jensen, Pierre Labauge, Olivier Casez, Peter Vestergaard Rasmussen, Bertrand Bourre, Olivier Heinzlef, Gilles Defer, Gilles Edan, Alessandra Lugaresi, Abir Wahab, Melinda Magyari, Anneke van der Walt, Eva Havrdova, Johanna Balslev Andersen, Chantal Nifle, Stephan Bramow, Marc Debouverie, Thibault Moreau, Sandra Vukusic, Christine Lebrun-Frenay, Jeannette Lechner-Scott, Eric Thouvenot, Sharmin S., Lefort M., Andersen J.B., Leray E., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand'Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Prevost J., Maimone D., Skibina O., Buzzard K., Van der Walt A., Van Wijmeersch B., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., De Seze J., Maillart E., Zephir H., Labauge P., Defer G., Lebrun-Frenay C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Laplaud D., Koch-Henriksen N., Sellebjerg F.T., Soerensen P.S., Pfleger C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Magyari M., Vukusic S., Butzkueven H., Kalincik T., University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), École des Hautes Études en Santé Publique [EHESP] (EHESP), Charles University [Prague] (CU), Amiri hospital, Hospital Virgen Macarena, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), University of Catania [Italy], G.F. Ingrassia Hospital, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Neurological Science of Bologna (IRCCS), Ondokuz Mayis University (OMU), American University of Beirut Faculty of Medicine and Medical Center (AUB), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Karadeniz Technical University (KTU), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Queensland [Brisbane], Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Flinders University [Adelaide, Australia], University of Newcastle [Callaghan, Australia] (UoN), Azienda Ospedaleria Universitaria di Modena, Università degli studi di Parma = University of Parma (UNIPR), University Hospital Parma, Monash University [Melbourne], The Alfred Hospital, Hasselt University (UHasselt), University of Debrecen Egyetem [Debrecen], San Giuseppe Moscati Hospital [Avellino, Italie], Westmead Hospital [Sydney], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Eugène Devic EDMUS, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Pasteur [Nice] (CHU), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHI Poissy-Saint-Germain, Service de neurologie [Amiens], CHU Amiens-Picardie, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], Service de Neurologie [CHU Limoges], CHU Limoges, CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Sud Francilien Corbeil Essonne, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Aarhus University Hospital, Aalborg University [Denmark] (AAU), University Hospital of Northern Sealand, Rigshospitalet [Copenhagen], Copenhagen University Hospital, The Royal Melbourne Hospital, 1140766, National Health and Medical Research Council, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (KU), Università degli Studi di Bologna, University of Bari Aldo Moro (UNIBA), University of Newcastle [Australia] (UoN), University of Parma = Università degli studi di Parma [Parme, Italie], University of Debrecen, Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Ondokuz Mayis University, Centre de recherche en neurosciences de Lyon (CRNL), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Internationality, Subgroup analysis, Rate ratio, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, 030225 pediatrics, Internal medicine, Secondary Prevention, Medicine, Humans, Immunologic Factors, Pharmacology (medical), Longitudinal Studies, Registries, 10. No inequality, Expanded Disability Status Scale, business.industry, Proportional hazards model, Fingolimod Hydrochloride, Multiple sclerosis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, medicine.disease, Fingolimod, 3. Good health, multiple sclerosis, sex, age, natalizumab, fingolimod, big data, Psychiatry and Mental health, Cohort, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract: Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined. Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest. Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients’ sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed withweighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score. Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15–41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65–0.88); in those aged ≤38 years (0.64; 0.54–0.76); in those withdisease duration ≤7 years (0.63; 0.53–0.76); in those with EDSS score 38 years (1.34; 1.04–1.73); those with disease duration >7 years (1.33; 1.01–1.74); those with EDSS score
Published: 2021

11. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

Author: Disanto, G1, Adiutori, R2, Dobson, R2, Martinelli, V3, Dalla Costa G3, Runia, T4, Evdoshenko, E5, Thouvenot, E6, Trojano, M7, Norgren, N8, Teunissen, C9, Kappos, L10, Giovannoni, G2, Kuhle, J, Bianchi, L, Topping, J, Bestwick, Jp, Meier, Uc, Lazareva, N, Iaffaldano, P, Direnzo, V, Khademi, M, Piehl, F, Comabella, M, Sombekke, M, Killestein, J, Hegen, H, Rauch, S, D'Alfonso, S, Alvarez-Cermeño, Jc, Kleinová, P, Horáková, D, Roesler, R, Lauda, F, Llufriu, S, Avsar, T, Uygunoglu, U, Altintas, A, Saip, S, Menge, T, Rajda, C, Bergamaschi, R, Moll, N, Khalil, M, Marignier, R, Dujmovic, I, Larsson, H, Malmestrom, C, Scarpini, E, Fenoglio, C, Wergeland, S, Laroni, A, Annibali, V, Romano, S, Martínez, Ad, Carra, A, Salvetti, M, Uccelli, A, Torkildsen, Ø, Myhr, Km, Galimberti, D, Rejdak, K, Lycke, J, Frederiksen, Jl, Drulovic, J, Confavreux, C, Brassat, D, Enzinger, C, Fuchs, S, Bosca, I, Pelletier, J, Picard, C, Colombo, E, Franciotta, D, Derfuss, T, Lindberg, Rl, Yaldizli, Ö, Vécsei, L, Kieseier, Bc, Hartung, Hp, Villoslada, P, Siva, A, Saiz, A, Tumani, H, Havrdová, E, Villar, Lm, Leone, M, Barizzone, N, Deisenhammer, F, Montalban, X, Tintoré, M, Olsson, T, Lehmann, S, Castelnovo, G, Lapin, S, Hintzen, R, Furlan, R, Comi, G, Ramagopalan, Sv., Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratory Medicine, Amsterdam Neuroscience - Neuroinfection & -inflammation, Disanto, G., Adiutori, R., Dobson, R., Martinelli, V., Dalla Costa, G., Runia, T., Evdoshenko, E., Thouvenot, E., Trojano, M., Norgren, N., Teunissen, C., Kappos, L., Giovannoni, G., Kuhle, J., on behalf of the International ClinicallyIsolated Syndrome Study, Group, and Neurology
Subjects: Male, Pathology, Future studies, Gastroenterology, 0302 clinical medicine, Neurofilament Proteins, Multiple Sclerosi, 0303 health sciences, Clinically isolated syndrome, medicine.diagnostic_test, Medicine (all), Neurofilament Protein, Demyelinating Disease, Magnetic Resonance Imaging, Psychiatry and Mental Health, Predictive value of tests, Disease Progression, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, Neurofilament light, multiple sclerosis, adult, axons, biomarkers, demyelinating diseases, disease progression, female, follow-up studies, humans, magnetic resonance imaging, male, neurofilament proteins, predictive value of tests, neurology (clinical), psychiatry and mental health, surgery, arts and humanities (miscellaneous), medicine (all), [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Axon, Follow-Up Studie, 03 medical and health sciences, Arts and Humanities (miscellaneous), Predictive Value of Tests, Internal medicine, medicine, Humans, In patient, MULTIPLE SCLEROSIS, 030304 developmental biology, business.industry, Multiple sclerosis, Magnetic resonance imaging, Biomarker, medicine.disease, Axons, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Surgery, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Demyelinating Diseases, Follow-Up Studies
Abstract: International audience; BACKGROUND:Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls.METHODS:We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3-7.9)); and 92 healthy controls.RESULTS:NfL levels were higher in FC (24.1 pg/mL (13.5-51.8)) and NC (19.3 pg/mL (13.6-35.2)) than in healthy controls (7.9 pg/mL (5.6-17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p = 1.5 × 10(-5) and OR = 7.03; 95% CI 2.85 to 17.34; p = 2.3 × 10(-5), respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR = 2.36; 95% CI 1.21 to 4.59; p = 0.011), gadolinium-enhancing lesions (OR = 2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR = 2.54; 95% CI 1.21 to 5.31; p = 0.013) at CIS diagnosis.CONCLUSIONS:If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.
Published: 2016

12. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

Author: Ruth Dobson, P. Kleinova, Tessel F. Runia, H.-P. Hartung, Maria Trojano, A.D. Martinez, Viviana Annibali, Sreeram V. Ramagopalan, Florian Deisenhammer, Mohsen Khademi, Jens Kuhle, Jan Lycke, Mar Tintoré, Ludwig Kappos, Pietro Iaffaldano, Antonio Uccelli, Dana Horakova, Kjell-Morten Myhr, Cecilia Rajda, Konrad Rejdak, Stig Wergeland, Monica Marta, Roberto Furlan, Florian Lauda, Jean Pelletier, Romain Marignier, G. Comi, Giulio Disanto, Romy Roesler, Vita Direnzo, Özgür Yaldizli, N. Moll, Silvia Romano, Sergey V. Lapin, Sylvain Lehmann, Irena Dujmovic, Elio Scarpini, Tomas Olsson, Rogier Q. Hintzen, Raija L.P. Lindberg, E. P. Evdoshenko, Siegrid Fuchs, B. C. Kieseier, Henrik Larsson, Eric Thouvenot, Jonathan P. Bestwick, Maurizio Leone, László Vécsei, S. Saip, Pablo Villoslada, Roberto Bergamaschi, Xavier Montalban, Øivind Torkildsen, José C. Álvarez-Cermeño, Joanne Topping, Albert Saiz, Isabel Bosca, Hayrettin Tumani, Adriana Carrá, Joep Killestein, Sara Llufriu, N. Barizzone, Ute-Christiane Meier, Diego Franciotta, David Brassat, Christian Enzinger, Michael Khalil, Gavin Giovannoni, Timucin Avsar, Scott L. Rauch, Aksel Siva, N. Lazareva, Clas Malmeström, Jette L. Frederiksen, Harald Hegen, Ugur Uygunoglu, Luisa M. Villar, Lucia Bianchi, Marco Salvetti, Tobias Derfuss, Giovanni Castelnovo, Ayse Altintas, Rocco Adiutori, E. Colombo, G. Dalla Costa, Daniela Galimberti, Madeleine H. Sombekke, Vittorio Martinelli, Sandra D'Alfonso, Manuel Comabella, Eva Havrdova, Fredrik Piehl, Charlotte E. Teunissen, Til Menge, Jelena Drulovic, C. Picard, Alice Laroni, Christian Confavreux, Chiara Fenoglio, Neurology, Laboratory Medicine, NCA - Neuroinflamation, Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), National Oceanography Centre (NOC), Department of Anatomy and Structural Biology Albert Einstein College of Medicine, Albert Einstein College of Medicine [New York], Department of public health, University of Turin, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Water Environment Technology, Chalmers University of Technology [Göteborg], Department of Neurology, A.O.U. Maggiore della Carità, and IRCAD, Novara, Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB), Leibniz Association, Department of Neurology, University of California [San Francisco] (UCSF), University of California-University of California, Center for Neuroimmunology, Service of Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Université européenne de Bretagne - European University of Brittany (UEB), Laboratoire de l'intégration, du matériau au système (IMS), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Azm Center for Biotechnology Research, Agence universitaire de la Francophonie (Beyrouth, Lebanon)-Lebanese University [Beirut] (LU), FOI, Linköping University (LIU), Centro Dino Ferrari [Milano], Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, IRMP-Louvain, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Dipartimento Ingegneria Aerospaziale 'Lucio Lazzarino' (DIA), University of Pisa - Università di Pisa, International Centre for Hydrology 'Dino Tonini' and Dipartimento IMAGE, Universita degli Studi di Padova, Dept. of Neurology, University Hospital Rigshospitalet, University of California [Berkeley], University of California, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Immunology, The Weizmann Institute, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Laboratory of Neuroimmunology, IRCCS, Neurological Institute 'C. Mondino', University of Pavia, Pa, University of Pavia, Department of Neurology, Albert Szent-Gyorgyi Clinical Centre, University of Szeged [Szeged], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Universitat de Barcelona (UB)-Hospital Clinic, University of Ulm, Department of Neurology, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], University of Eastern Piedmont, Department of Medical Sciences, IRCAD, Novara, Vall d'Hebron University Hospital [Barcelona], Department of Public Health and Clinical Medicine, Umeå University, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Universitaire de Bâle, Laboratory of Molecular Virology, Université libre de Bruxelles (ULB), Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Department of Atmospheric, Oceanic and Planetary Physics [Oxford] (AOPP), University of Oxford [Oxford], Blizard Institute of Cell and Molecular Science, Università degli studi di Torino = University of Turin (UNITO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), University of California [Berkeley] (UC Berkeley), University of California (UC), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Pavia = University of Pavia (UNIPV), University of Oxford, Direction des Applications Militaires ( DAM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), National Oceanography Centre, University of Southampton [Southampton], Albert Einstein College of Medicine, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Neuropsychiatrie : recherche épidémiologique et clinique, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Leibniz-Institute, University of California [San Francisco] ( UCSF ), Université européenne de Bretagne ( UEB ), Laboratoire de l'intégration, du matériau au système ( IMS ), Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique ( CNRS ), Agence universitaire de la Francophonie (Beyrouth, Lebanon)-Lebanese University [Beirut], Linköping University ( LIU ), Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy, Università di Bologna [Bologna] ( UNIBO ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Dipartimento Ingegneria Aerospaziale 'Lucio Lazzarino' ( DIA ), Università di Pisa, Universita degli Studi di Padova = University of Padua = Université de Padoue, Educational Testing Service, Graduate School of Education, University of California at Berkeley, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Centre de résonance magnétique biologique et médicale ( CRMBM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Centre National de la Recherche Scientifique ( CNRS ), Universitat de Barcelona ( UB ) -Hospital Clinic, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Institut de recherche en biothérapie ( IRB ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Université de Montpellier ( UM ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Department of Atmospheric, Oceanic and Planetary Physics [Oxford] ( AOPP ), Kuhle, J., Disanto, G., Dobson, R., Adiutori, R., Bianchi, L., Topping, J., Bestwick, J. P., Meier, U. -C., Marta, M., Dalla Costa, G, Runia, T., Evdoshenko, E., Lazareva, N., Thouvenot, E., Iaffaldano, P., Direnzo, V., Khademi, M., Piehl, F., Comabella, M., Sombekke, M., Killestein, J., Hegen, H., Rauch, S., Dalfonso, S., Alvarez-Cermeno, J. C., Kleinova, P., Horakova, D., Roesler, R., Lauda, F., Llufriu, S., Avsar, T., Uygunoglu, U., Altintas, A., Saip, S., Menge, T., Rajda, C., Bergamaschi, R., Moll, N., Khalil, M., Marignier, R., Dujmovic, I., Larsson, H., Malmestrom, C., Scarpini, E., Fenoglio, C., Wergeland, S., Laroni, A., Annibali, V., Romano, S., Martinez, A. D., Carra, A., Salvetti, M., Uccelli, A., Torkildsen, O., Myhr, K. M., Galimberti, D., Rejdak, K., Lycke, J., Frederiksen, J. L., Drulovic, J., Confavreux, C., Brassat, D., Enzinger, C., Fuchs, S., Bosca, I., Pelletier, J., Picard, C., Colombo, E., Franciotta, D., Derfuss, T., Lindberg, R. L. P., Yaldizli, O., Vecsei, L., Kieseier, B. C., Hartung, H. P., Villoslada, P., Siva, A., Saiz, A., Tumani, H., Havrdova, E., Villar, L. M., Leone, M., Barizzone, N., Deisenhammer, F., Teunissen, C., Montalban, X., Tintore, M., Olsson, T., Trojano, M., Lehmann, S., Castelnovo, G., Lapin, S., Hintzen, R., Kappos, L., Furlan, R., Martinelli, V., Comi, G., Ramagopalan, S. V., and Giovannoni, G.
Subjects: Male, Pathology, serum 25-hydroxyvitamin D3 (25-OH-D), [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Gastroenterology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, sclerosis, clinically isolated syndrome (CIS), Vitamin D, 0303 health sciences, Clinically isolated syndrome, Nuclear Proteins, Prognosis, Magnetic Resonance Imaging, Neurology, Clinically definite multiple sclerosis (CDMS), Epstein-Barr nuclear antigen 1 (EBNA-1), oligoclonal bands (OCBs), Predictive value of tests, Cohort, Disease Progression, Female, Cohort study, Adult, medicine.medical_specialty, Multiple Sclerosis, clinic study, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Vitamin D and neurology, Humans, Survival analysis, 030304 developmental biology, business.industry, Multiple sclerosis, Oligoclonal Bands, Endonucleases, medicine.disease, Survival Analysis, chemistry, Immunoglobulin G, [ SHS.ANTHRO-BIO ] Humanities and Social Sciences/Biological anthropology, Neurology (clinical), business, Cotinine, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
Published: 2015

13. Delay from treatment start to full effect of immunotherapies for multiple sclerosis

Author: Roos, Izanne, Leray, Emmanuelle, Frascoli, Federico, Casey, Romain, Brown, J William L, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Patti, Francesco, Izquierdo, Guillermo, Eichau, Sara, Onofrj, Marco, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ozakbas, Serkan, Bergamaschi, Roberto, Sá, Maria José, Cartechini, Elisabetta, Boz, Cavit, Granella, Franco, Hupperts, Raymond, Terzi, Murat, Lechner-Scott, Jeannette, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Olascoaga, Javier, Prevost, Julie, Aguera-Morales, Eduardo, Slee, Mark, Csepany, Tunde, Turkoglu, Recai, Sidhom, Youssef, Gouider, Riadh, Van Wijmeersch, Bart, McCombe, Pamela, Macdonell, Richard, Coles, Alasdair, Malpas, Charles, Butzkueven, Helmut, Vukusic, Sandra, Kalincik, Tomas, Duquette, Pierre, Grand'Maison, Francois, Iuliano, Gerardo, Ramo-Tello, Cristina, Solaro, Claudio, Cabrera-Gomez, Jose Antonio, Rio, Maria Edite, Bolaños, Ricardo Fernandez, Shaygannejad, Vahid, Oreja-Guevara, Celia, Sanchez-Menoyo, Jose Luis, Petersen, Thor, Altintas, Ayse, Barnett, Michael, Flechter, Shlomo, Fragoso, Yara, Amato, Maria Pia, Moore, Fraser, Ampapa, Radek, Verheul, Freek, Hodgkinson, Suzanne, Cristiano, Edgardo, Yamout, Bassem, Laureys, Guy, Dominguez, Jose Andres, Zwanikken, Cees, Deri, Norma, Dobos, Eniko, Vrech, Carlos, Butler, Ernest, Rozsa, Csilla, Petkovska-Boskova, Tatjana, Karabudak, Rana, Rajda, Cecilia, Alkhaboori, Jabir, Saladino, Maria Laura, Shaw, Cameron, Shuey, Neil, Vucic, Steve, Sempere, Angel Perez, Campbell, Jamie, Piroska, Imre, Taylor, Bruce, van der Walt, Anneke, Kappos, Ludwig, Roullet, Etienne, Gray, Orla, Simo, Magdolna, Sirbu, Carmen-Adella, Brochet, Bruno, Cotton, François, De Sèze, Jérôme, Dion, Armelle, Douek, Pascal, Guillemin, Francis, Laplaud, David, Lebrun-Frenay, Christine, Moreau, Thibault, Olaiz, Javier, Pelletier, Jean, Rigaud-Bully, Claire, Stankoff, Bruno, Marignier, Romain, Debouverie, Marc, Edan, Gilles, Ciron, Jonathan, Ruet, Aurélie, Collongues, Nicolas, Lubetzki, Catherine, Vermersch, Patrick, Labauge, Pierre, Defer, Gilles, Cohen, Mikaël, Fromont, Agnès, Wiertlewsky, Sandrine, Berger, Eric, Clavelou, Pierre, Audoin, Bertrand, Giannesini, Claire, Gout, Olivier, Thouvenot, Eric, Heinzlef, Olivier, Al-Khedr, Abdullatif, Bourre, Bertrand, Casez, Olivier, Cabre, Philippe, Montcuquet, Alexis, Créange, Alain, Camdessanché, Jean-Philippe, Faure, Justine, Maurousset, Aude, Patry, Ivania, Hankiewicz, Karolina, Pottier, Corinne, Maubeuge, Nicolas, Labeyrie, Céline, Nifle, Chantal, University of Melbourne, The Royal Melbourne Hospital, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Swinburne University of Technology [Melbourne], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, University of Cambridge [UK] (CAM), Medicine Charles University and General Faculty Hospital in Prague, University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Hospital Universitario Virgen Macarena [Seville, Spain], University 'G. d'Annunzio' of Chieti-Pescara [Chieti], Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Université de Montréal (UdeM), University of Modena and Reggio Emilia, Partenaires INRAE, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), IRCCS Mondino Foundation, Universidade Fernando Pessoa, KTU Medical Faculty Farabi Hospital, University of Parma = Università degli studi di Parma [Parme, Italie], Zuyderland Ziekenhuis, Medical Faculty [Samsun, Turkey], University of Newcastle [Australia] (UoN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Hospital Universitario Donostia, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Haydarpasa Numune Training and Research Hospital, Hasselt University (UHasselt), University of Queensland [Brisbane], Hitachi Cambridge Laboratory [University of Cambridge], Hitachi, Ltd-University of Cambridge [UK] (CAM), Monash University [Melbourne], Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Ospedali Riuniti di Salerno, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 1157717, National Health and Medical Research Council, Biogen, MSIF-ARSEP McDonald, Melbourne Research Scholarship, French State, ‘Agence Nationale de la Recherche,’, ANR-10-COHO-002, ‘Investments for the Future’, Eugène Devic EDMUS Foundation, ARSEP Foundation, Novartis, Merck, Roche, Teva Pharmaceutical Industries, Sanofi Genzyme, EDMUS Foundation, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Roos I., Leray E., Frascoli F., Casey R., Brown W.J.L., Horakova D., Havrdova E.K., Trojano M., Patti F., Izquierdo G., Eichau S., Onofrj M., Lugaresi A., Prat A., Girard M., Grammond P., Sola P., Ferraro D., Ozakbas S., Bergamaschi R., Sa M.J., Cartechini E., Boz C., Granella F., Hupperts R., Terzi M., Lechner-Scott J., Spitaleri D., van Pesch V., Soysal A., Olascoaga J., Prevost J., Aguera-Morales E., Slee M., Csepany T., Turkoglu R., Sidhom Y., Gouider R., van Wijmeersch B., McCombe P., Macdonell R., Coles A., Malpas C.B., Butzkueven H., Vukusic S., Kalincik T., Duquette P., Grand'Maison F., Iuliano G., Ramo-Tello C., Solaro C., Cabrera-Gomez J.A., Rio M.E., Bolanos R.F., Shaygannejad V., Oreja-Guevara C., Sanchez-Menoyo J.L., Petersen T., Altintas A., Barnett M., Flechter S., Fragoso Y., Amato M.P., Moore F., Ampapa R., Verheul F., Hodgkinson S., Cristiano E., Yamout B., Laureys G., Dominguez J.A., Zwanikken C., Deri N., Dobos E., Vrech C., Butler E., Rozsa C., Petkovska-Boskova T., Karabudak R., Rajda C., Alkhaboori J., Saladino M.L., Shaw C., Shuey N., Vucic S., Sempere A.P., Campbell J., Piroska I., Taylor B., van der Walt A., Kappos L., Roullet E., Gray O., Simo M., Sirbu C.-A., Brochet B., Cotton F., de Seze J., Dion A., Douek P., Guillemin F., Laplaud D., Lebrun-Frenay C., Moreau T., Olaiz J., Pelletier J., Rigaud-Bully C., Stankoff B., Marignier R., Debouverie M., Edan G., Ciron J., Ruet A., Collongues N., Lubetzki C., Vermersch P., Labauge P., Defer G., Cohen M., Fromont A., Wiertlewsky S., Berger E., Clavelou P., Audoin B., Giannesini C., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Creange A., Camdessanche J.-P., Faure J., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Brown, Will [0000-0002-7737-5834], Coles, Alasdair [0000-0003-4738-0760], Apollo - University of Cambridge Repository, McCombe, Pamela/0000-0003-2704-8517, Slee, Mark/0000-0003-4323-2453, Brown, William/0000-0002-7737-5834, Laplaud, David/0000-0001-6113-6938, Ciron, Jonathan/0000-0002-3386-6308, Roos, Izanne/0000-0003-0371-3666, Lugaresi, Alessandra/0000-0003-2902-5589, Aguera-Morales, Eduardo/0000-0002-8604-2054, Kalincik, Tomas, Girard, Marc, Patti, Francesco, Horakova, Dana, Malpas, Charles B., Olascoaga, Javier, Prevost, Julie, Roos, Izanne, Hupperts, Raymond, Csepany, Tunde, VAN WIJMEERSCH, Bart, Ferraro, Diana, Aguera-Morales, Eduardo, Cartechini, Elisabetta, Vukusic, Sandra, Frascoli, Federico, Lugaresi, Alessandra, Sa, Maria Jose, Butzkueven, Helmut, Spitaleri, Daniele, Macdonell, Richard, Coles, Alasdair, Havrdova, Eva K., Granella, Franco, Turkoglu, Recai, Trojano, Maria, Sola, Patrizia, Van Pesch, Vincent, Onofrj, Marco, Grammond, Pierre, Bergamaschi, Roberto, Izquierdo, Guillermo, McCombe, Pamela, Slee, Mark, Eichau, Sara, Prat, Alexandre, Leray, Emmanuelle, Soysal, Aysun, Terzi, Murat, Brown, J. William L., Boz, Cavit, Sidhom, Youssef, Gouider, Riadh, Ozakbas, Serkan, Casey, Romain, Lechner-Scott, Jeannette, Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Hospital Universitario Virgen Macarena [Séville], Università degli studi di Parma = University of Parma (UNIPR), University of Newcastle [Callaghan, Australia] (UoN), University of Cambridge [UK] (CAM)-Hitachi, Ltd, and ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010)
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Time Factors, multiple sclerosis, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Randomized controlled trial, law, Internal medicine, medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Prospective Studies, Registries, Prospective cohort study, therapeutic lag, business.industry, Multiple sclerosis, Interferon beta-1a, Middle Aged, medicine.disease, Fingolimod, 3. Good health, Treatment Outcome, Cohort, Disease Progression, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Immunotherapies, 030217 neurology & neurosurgery, Immunosuppressive Agents, Therapeutic lag, prognosis, treatment, medicine.drug, Cohort study, Follow-Up Studies
Abstract: In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag. This study was supported by the EDMUS Foundation, Biogen and NHMRC (1140766, 1129189, 1157717). I.R. is supported by a MSIF-ARSEP McDonald fellowship grant and a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The Observatoire Francais de la Sclerose en Plaques (OFSEP) is supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002, by the Eugene Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. The study was conducted separately and apart from the guidance of the sponsors. Kalincik, T (corresponding author), Univ Melbourne, Dept Med, CORe, 300 Grattan St, Melbourne, Vic 3050, Australia. tomas.kalincik@unimelb.edu.au

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13 results on '"Thouvenot E."'

1. Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

2. Radiologically Isolated Syndrome: 10-Year Risk Estimate of a Clinical Event

3. Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults

4. Rivaroxaban for stroke prevention after embolic stroke of undetermined source

5. Epstein-Barr-negative MS: a true phenomenon?

6. Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

7. Comparative efficacy of fingolimod vs natalizumab: A French multicenter observational study

8. The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

9. Determinants of therapeutic lag in multiple sclerosis

10. Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts

11. Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome

12. Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

13. Delay from treatment start to full effect of immunotherapies for multiple sclerosis

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