34 results on '"Castillo-Trivino T"'
Search Results
2. Experiencia con tocilizumab en pacientes con espectro de la neuromielitis óptica
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Carreón Guarnizo, E., Hernández Clares, R., Castillo Triviño, T., Meca Lallana, V., Arocas Casañ, V., Iniesta Martínez, F., Olascoaga Urtaza, J., and Meca Lallana, J.E.
- Published
- 2022
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3. Development and validation of a brief electronic screening test for cognitive impairment in multiple sclerosis (SCI-MS Test)
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Meca-Lallana, J.E., Prieto-González, J.M., Jimenez-Veiga, J., Carreón-Guarnizo, E., Jiménez-Martín, I., Hernández-Clares, R., Sistiaga-Berrondo, A., Carles-Dies, R., García-Molina, E., Cerdán-Sánchez, M., Costa-Arpín, E., Croitoru, I., Castillo-Triviño, T., Iniesta-Martinez, F., García-Pérez, E., and Olascoaga-Urtaza, J.
- Published
- 2019
- Full Text
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4. Rituximab in Relapsing and Progressive Forms of Multiple Sclerosis: A Systematic Review
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Bacchetti, Peter, Braithwaite, Dejana, Waubant, Emmanuelle, and Castillo-Trivino, T
- Abstract
Background: Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS. Objectives: To evaluate the efficacy and safety of rituximab for MS treatment. Data collec
- Published
- 2013
5. Early non-disabling relapses are associated with a higher risk of disability accumulation in people with relapsing-remitting multiple sclerosis
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Coles, A., Daruwalla, C., Shaygannejad, V., Ozakbas, S., Havrdova, E. K., Alroughani, R., Patti, F., Onofrj, M., Eichau, S., Girard, M., Grand'Maison, F., Yamout, B., Sajedi, S. A., Amato, M. P., Altintas, A., Skibina, O., Grammond, P., Butzkueven, H., Maimone, D., Lechner-Scott, J., Soysal, A., John, N., Gerlach, O., Iuliano, G., Foschi, M., Van Pesch, V., Cartechini, E., Kuhle, J., Sa, M. J., Kermode, A., Gouider, R., Hodgkinson, S., McCombe, P., Sanchez-Menoyo, J. L., Singhal, B., Blanco, Y., Hughes, S., McGuigan, C., Taylor, B., Habek, M., Al-Asmi, A., Mihaela, S., Castillo Trivino, T., Al-Harbi, T., Rojas, J. I., Gray, O., Khurana, D., Van Wijmeersch, B., Kalincik, T., and Brown, J. W. L.
- Published
- 2022
6. Processing speed in early-stage relapsing-remitting multiple sclerosis and its influence on treatment decision making
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Saposnik G, Gomez-Ballesteros R, Borges M, Martin-Martinez J, Sotoca J, Alonso A, Caminero A, Borrega L, Sanchez-Menoyo J, Barrero-Hernandez F, Calles C, Brieva L, Blasco-Quilez M, Garcia-Soto J, Campo-Amigo M, Navarro-Canto L, Aguera E, Garces-Redondo M, Carmona O, Gabaldon-Torre L, Forero L, Hervas M, Maurino J, Castillo-Trivino T, and de la Maza S
- Published
- 2022
7. Self-reported and clinician-rated measures in multiple sclerosis care: looking for a complementary assessment approach
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de la Maza S, Gomez-Ballesteros R, Borges M, Martin-Martinez J, Sotoca J, Alonso A, Caminero A, Borrega L, Sanchez-Menoyo J, Barrero-Hernandez F, Calles C, Brieva L, Blasco-Quilez M, Garcia-Soto J, Del Campo-Amigo M, Navarro-Canto L, Agura E, Garces-Redondo M, Carmona O, Gabaldon-Torres L, Forero L, Hervas M, Maurino J, and Castillo-Trivino T
- Published
- 2022
8. Pregnancy in a modern day multiple sclerosis cohort: predictors of postpartum relapse and disability progression
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Jokubaitis, V., Yeh, W., Widyastuti, P., Stankovich, J., Gresle, M., Havrdova, E. Kubala, Horakova, D., Vodehnalova, K., Ozakbas, S., Madueno, S. Eichau, Duquette, P., Kalincik, T., Patti, F., Boz, C., Terzi, M., Yamout, B., Lechner-Scott, J., Sola, P., Skibina, O., Barnett, M., Onofrj, M., Sa, M. J., Mccombe, P., Grammond, P., Ampapa, R., Grand Maison, F., Bergamaschi, R., Spitaleri, D., Pesch, V., Cartechini, E., Hodgkinson, S., Soysal, A., Saiz, A., Uher, T., Maimone, D., Turkoglu, R., Hupperts, R., Amato, M. P., Granella, F., Eva Kubala Havrdova, Altintas, A., Macdonell, R., Castillo-Trivino, T., Butzkueven, H., Alroughani, R., and Walt, A.
- Published
- 2020
9. Pregnancy in a modern day multiple sclerosis cohort: predictors of relapse during pregnancy
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Yeh, W., Widyastuti, P., Walt, A., Stankovich, J., Gresle, M., Havrdova, E., Horakova, D., Vodehnalova, K., Ozakbas, S., Eichau, S., Duquette, P., Kalincik, T., Patti, F., Boz, C., Terzi, M., Yamout, B., Lechner-Scott, J., Sola, P., Skibina, O., Barnett, M., Onofrj, M., Sa, M. J., Mccombe, P., Grammond, P., Ampapa, R., Grand Maison, F., Bergamaschi, R., Spitaleri, D., Pesch, V., Cartechini, E., Hodgkinson, S., Soysal, A., Saiz, A., Uher, T., Maimone, D., Turkoglu, R., Hupperts, R., Amato, M. P., Granella, F., Eva Kubala Havrdova, Altintas, A., Macdonell, R., Castillo-Trivino, T., Butzkueven, H., Alroughani, R., and Jokubaitis, V.
- Published
- 2020
10. O Group is a protective factor for COVID19 in Basque population
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Muñoz-Culla, M, primary, Roncancio-Clavijo, A, additional, Martínez, B, additional, Gorostidi, M, additional, Piñeiro, L, additional, Azkune, A, additional, Alberro, A, additional, Monge-Ruiz, J, additional, Castillo-Trivino, T, additional, Prada, A, additional, and Otaegui, D, additional
- Published
- 2020
- Full Text
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11. Familial multiple sclerosis: comparing demographic and clinical characteristics with sporadic form
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Rojas, I., Sirbu-Adella, C., Ferraro, D., Luliano, G., Van Pesch, V., Izquierdo, G., Spelman, T., Eichau, S., Alroughani, R., Boz, C., Larochelle, C., Sanchez Menoyo, J. L., Butzkueven, H., Oreja-Guevara, C., Cartechini, E., Duquette, P., Girard, M., Trojano, M., Sola, P., Pucci, E., Vella, N., Castillo Trivino, T., Frogoso, Y., Petkovska-Boskova, T., Laffaldano, P., Terzi, M., and Ozakbas, SERKAN
- Published
- 2018
12. Hopelessness in Patients with Early-Stage Relapsing-Remitting Multiple Sclerosis
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Sainz de la Maza S, Maurino J, Castillo-Triviño T, Borges M, Sebastián Torres B, Sotoca J, Alonso Torres AM, Caminero AB, Borrega L, Sánchez-Menoyo JL, Barrero-Hernández FJ, Calles C, Brieva L, Blasco MR, Dotor García-Soto J, Rodríguez-Regal A, Navarro-Cantó L, Agüera-Morales E, Garcés M, Carmona O, Gabaldón-Torres L, Forero L, Hervás M, and Gómez-Ballesteros R
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relapsing-remitting multiple sclerosis ,hopelessness ,depressive symptoms ,workplace difficulties ,suicide ,Medicine (General) ,R5-920 - Abstract
Susana Sainz de la Maza,1 Jorge Maurino,2 Tamara Castillo-Triviño,3 Mónica Borges,4 Berta Sebastián Torres,5 Javier Sotoca,6 Ana María Alonso Torres,7 Ana B Caminero,8 Laura Borrega,9 José L Sánchez-Menoyo,10 Francisco J Barrero-Hernández,11 Carmen Calles,12 Luis Brieva,13 María Rosario Blasco,14 Julio Dotor García-Soto,4 Ana Rodríguez-Regal,15 Laura Navarro-Cantó,16 Eduardo Agüera-Morales,17 Moisés Garcés,18 Olga Carmona,19 Laura Gabaldón-Torres,20 Lucía Forero,21 Mariona Hervás,22 Rocío Gómez-Ballesteros2 1Department of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain; 2Medical Department, Roche Farma, Madrid, Spain; 3Department of Neurology, Hospital Universitario Donostia, San Sebastián, Spain; 4Department of Neurology, Hospital Universitario Virgen Macarena, Sevilla, Spain; 5Department of Neurology, Hospital Universitario Miguel Servet, Zaragoza, Spain; 6Department of Neurology, Hospital Universitari Vall d´Hebrón, Barcelona, Spain; 7Department of Neurology, Hospital Regional Universitario de Málaga, Málaga, Spain; 8Department of Neurology, Complejo Asistencial de Ávila, Ávila, Spain; 9Department of Neurology, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain; 10Department of Neurology, Hospital de Galdakao-Usansolo, Galdakao, Spain; 11Department of Neurology, Hospital Universitario Clínico San Cecilio, Granada, Spain; 12Department of Neurology, Hospital Universitari Son Espases, Palma de Mallorca, Spain; 13Department of Neurology, Hospital Universitari Arnau de Vilanova, Lleida, Spain; 14Department of Neurology, Hospital Universitario Puerta de Hierro, Madrid, Spain; 15Department of Neurology, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain; 16Department of Neurology, Hospital General Universitario de Elche, Elche, Spain; 17Department of Neurology, Hospital Universitario Reina Sofía, Córdoba, Spain; 18Department of Neurology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; 19Department of Neurology, Fundació Salut Empordà, Figueres, Spain; 20Department of Neurology, Hospital Francesc de Borja, Gandía, Spain; 21Department of Neurology, Hospital Universitario Puerta del Mar, Cádiz, Spain; 22Department of Neurology, Consorci Corporació Sanitària Parc Taulí, Sabadell, SpainCorrespondence: Jorge Maurino, Medical Department, Roche Farma, Ribera del Loira, 50, Madrid, 28042, Spain, Tel +34 913 24 81 00, Email jorge.maurino@roche.comBackground: Hopelessness is a risk factor for depression and suicide. There is little information on this phenomenon among patients with relapsing-remitting multiple sclerosis (RRMS), one of the most common causes of disability and loss of autonomy in young adults. The aim of this study was to assess state hopelessness and its associated factors in early-stage RRMS.Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0– 5.5 were included. The State-Trait Hopelessness Scale (STHS) was used to measure patients´ hopelessness. A battery of patient-reported and clinician-rated measurements was used to assess clinical status. A multivariate logistic regression analysis was conducted to determine the association between patients’ characteristics and state hopelessness.Results: A total of 189 patients were included. Mean age (standard deviation-SD) was 36.1 (9.4) years and 71.4% were female. Median disease duration (interquartile range-IQR) was 1.4 (0.7, 2.1) years. Symptom severity and disability were low with a median EDSS (IQR) score of 1.0 (0, 2.0). A proportion of 65.6% (n=124) of patients reported moderate-to-severe hopelessness. Hopelessness was associated with older age (p=0.035), depressive symptoms (p=< 0.001), a threatening illness perception (p=0.001), and psychological and cognitive barriers to workplace performance (p=0.029) in the multivariate analysis after adjustment for confounders.Conclusion: Hopelessness was a common phenomenon in early-stage RRMS, even in a population with low physical disability. Identifying factors associated with hopelessness may be critical for implementing preventive strategies helping patients to adapt to the new situation and cope with the disease in the long term.Keywords: relapsing-remitting multiple sclerosis, hopelessness, depressive symptoms, workplace difficulties, suicide
- Published
- 2023
13. POSA139 Measuring Productivity Loss in Early-Stage Relapsing-Remitting Multiple Sclerosis
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Sainz de la Maza, S, Gómez-Ballesteros, R, Borges, M, Ruiz de Alda, L, Maurino, J, and Castillo-Triviño, T
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- 2022
- Full Text
- View/download PDF
14. PND22 Discover Study, First Analysis Specific for Secondary Progressive Multiple Sclerosis Burden and Cost in Spain: Interim Analysis Results
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Oreja-Guevara, C., Río Izquierdo, J., Ara Callizo, J.R., Hernández-Pérez, M.A., Gracia Gil, J., Pilo de la Fuente, B., Ramió-Torrentà, L., Alonso Torres, A.M., Eichau, S., Martínez Yélamos, S., Casanova Estruch, B., Gascón Giménez, F., Aguado Valcárcel, M.L., Martínez Ginés, M.L., López de Silanes, C., El Berdei Montero, Y., López Real, A.M., Martínez Rodríguez, J.E., González Quintanilla, V., Labiano Fontcuberta, A., Costa-Frossard França, L., Garcés Redondo, M., García Merino, J.A., Castellanos Pinedo, F., Meca-Lallana, V., Muñoz Fernández, C., Castillo Triviño, T., Rodríguez, A., Peña Martínez, J., Prieto González, J.M., Solar Sánchez, D.M., Agüera Morales, E., Molina, M.I., Herrera Varo, N., Aguirre Vazquez, M., and Meca-Lallana, J.
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- 2020
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15. Clinical and demographic predictors of response to first-line therapies in relapsing-remitting multiple sclerosis
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Castillo Trivino, T., Gajofatto, Alberto, and Waubant, E.
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multiple sclerosis - Published
- 2011
16. Long lesions on initial spinal cord MRI predict a final diagnosis of acute disseminated encephalomyelitis versus multiple sclerosis in children
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Mowry, E., Gajofatto, Alberto, Blasco, M. R., Castillo Trivino, T., Chabas, D., and Waubant, E.
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acute disseminated encephalomyelitis ,multiple sclerosis - Published
- 2008
17. Relapse Related Differentially Expressed microRNA May Have a Role in Immunological Processes in MS (P02.099)
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Munoz-Culla, M., primary, Irizar, H., additional, Castillo-Trivino, T., additional, Zuriarrain, O., additional, Lopez De Munain, A., additional, Olaskoaga Urtaza, J., additional, and Otaegui, D., additional
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- 2012
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18. Vanishing MS T2-bright lesions before puberty: A distinct MRI phenotype?
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Chabas, D., primary, Castillo-Trivino, T., additional, Mowry, E. M., additional, Strober, J. B., additional, Glenn, O. A., additional, and Waubant, E., additional
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- 2008
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19. Disability accrual in primary-progressive & secondary-progressive multiple sclerosis
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Harding-Forrester, S., Izanne Roos, Sharmin, S., Diouf, I., Malpas, C., Nguyen, A. -L, Moradi, N., Horakova, D., Havrdova, E. Kubala, Patti, F., Izquierdo, G., Eichau, S., Prat, A., Girard, M., Duquette, P., Onofrj, M., Lugaresi, A., Grand Maison, F., Weinstock-Guttman, B., Amato, M. P., Grammond, P., Gerlach, O., Ozakbas, S., Sola, P., Ferraro, D., Butzkueven, H., Lechner-Scott, J., Boz, C., Alroughani, R., Pesch, V., Cartechini, E., Terzi, M., Maimone, D., Ramo-Tello, C., Spitaleri, D., Kappos, L., Yamout, B., Sa, M., Slee, M., Blanco, Y., Bergamaschi, R., Butler, E., Iuliano, G., Granella, F., Sidhom, Y., Gouider, R., Ampapa, R., Wijmeersch, B., Karabudak, R., Prevost, J., Sanchez-Menoyo, J. L., Verheul, F., Mccombe, P., Castillo-Trivino, T., Macdonell, R., Altintas, A., Laureys, G., Hijfte, L., Walt, A., Vucic, S., Turkoglu, R., Barnett, M., Cristiano, E., Zakaria, M., Shaygannejad, V., Hodgkinson, S., Soysal, A., and Kalincik, T.
20. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis
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Diouf, I, Malpas, C, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Zakaria, M, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Hamdy, S, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Butzkueven, H, Yamout, B, Altintas, A, Van Pesch, V, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Giuliano, F, Mcguigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, M, Kappos, L, Ramo-Tello, C, Cristiano, E, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Slee, M, Butler, E, Granella, F, Verheul, F, Mccombe, P, Ampapa, R, Skibina, O, Prevost, J, Sinnige, LGF, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Van Hijfte, L, Khurana, D, Macdonell, R, Castillo-Trivino, T, Gray, O, Aguera, E, Kister, I, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, A, and Kalincik, T
21. Determinants of therapeutic lag in multiple sclerosis
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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)
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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
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- 2021
22. Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.
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Lunemann JD, Hegen H, Villar LM, Rejdak K, Sao-Aviles A, Carbonell-Mirabent P, Sastre-Garriga J, Mongay-Ochoa N, Berek K, Martínez-Yélamos S, Pérez-Miralles F, Abdelhak A, Bachhuber F, Tumani H, Lycke JN, Rosenstein I, Alvarez-Lafuente R, Castillo-Trivino T, Otaegui D, Llufriu S, Blanco Y, Sánchez López AJ, Garcia Merino JA, Fissolo N, Gutierrez L, Villacieros-Álvarez J, Monreal E, Valls-Carbó A, Wiendl H, Montalban X, and Comabella M
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- Humans, Male, Female, Middle Aged, Adult, Follow-Up Studies, Complement C3 metabolism, Complement C3 analysis, Complement C3a metabolism, Complement C3a cerebrospinal fluid, Disability Evaluation, Complement System Proteins cerebrospinal fluid, Complement System Proteins metabolism, Disease Progression, Multiple Sclerosis, Chronic Progressive cerebrospinal fluid, Multiple Sclerosis, Chronic Progressive blood, Multiple Sclerosis, Chronic Progressive physiopathology
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Background and Objectives: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS)., Methods: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up)., Results: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025)., Discussion: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.
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- 2024
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23. Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis.
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Fissolo N, Benkert P, Sastre-Garriga J, Mongay-Ochoa N, Vilaseca-Jolonch A, Llufriu S, Blanco Y, Hegen H, Berek K, Perez-Miralles F, Rejdak K, Villar LM, Monreal E, Alvarez-Lafuente R, Soylu OK, Abdelhak A, Bachhuber F, Tumani H, Martínez-Yélamos S, Sánchez-López AJ, García-Merino A, Gutiérrez L, Castillo-Trivino T, Lycke J, Rosenstein I, Furlan R, Filippi M, Téllez N, Ramió-Torrentà L, Lünemann JD, Wiendl H, Eichau S, Khalil M, Kuhle J, Montalban X, and Comabella M
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- Male, Humans, Middle Aged, Female, Biomarkers, Neurofilament Proteins, Glial Fibrillary Acidic Protein, Disease Progression, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Disabled Persons
- Abstract
Background: We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS)., Methods: A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods., Results: Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change., Conclusions: Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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24. Effectiveness of multiple disease-modifying therapies in relapsing-remitting multiple sclerosis: causal inference to emulate a multiarm randomised trial.
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Diouf I, Malpas CB, Sharmin S, Roos I, Horakova D, Kubala Havrdova E, Patti F, Shaygannejad V, Ozakbas S, Eichau S, Onofrj M, Lugaresi A, Alroughani R, Prat A, Duquette P, Terzi M, Boz C, Grand'Maison F, Sola P, Ferraro D, Grammond P, Yamout B, Altintas A, Gerlach O, Lechner-Scott J, Bergamaschi R, Karabudak R, Iuliano G, McGuigan C, Cartechini E, Hughes S, Sa MJ, Solaro C, Kappos L, Hodgkinson S, Slee M, Granella F, de Gans K, McCombe PA, Ampapa R, van der Walt A, Butzkueven H, Sánchez-Menoyo JL, Vucic S, Laureys G, Sidhom Y, Gouider R, Castillo-Trivino T, Gray O, Aguera-Morales E, Al-Asmi A, Shaw C, Al-Harbi TM, Csepany T, Sempere AP, Treviño Frenk I, Stuart EA, and Kalincik T
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- Humans, Pregnancy, Female, Glatiramer Acetate therapeutic use, Fingolimod Hydrochloride therapeutic use, Immunosuppressive Agents therapeutic use, Natalizumab therapeutic use, Dimethyl Fumarate therapeutic use, Interferon-beta therapeutic use, Recurrence, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis drug therapy
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Background: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years., Methods: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement., Results: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability., Conclusions: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously., Competing Interests: Competing interests: The authors report the following relationships: speaker honoraria, advisory board or steering committee fees, research support and/or conference travel support from Acthelion (EKH, RA), Almirall (MT, FG, RB, CRT, JLS-M), Bayer (MT, AL, PS, RA, MT, CB, JL-S, EP, VVP, RB, DS, RA, JO, JLSM, SH, CR, AGK, TC, NS, BT, MS, CAS), BioCSL (TK, AGK, BT), Biogen (TK, TS, DH, EKH, MT, GI, AL, MG, PD, PG, VJ, AVW, FG, PS, DF, RA, RH, CB, JLS, EP, VVP, FG, RB, RA, CRT, JP, JO, MB, JLSM, SH, CR, CSh, OGerlach, AGK, TC, BS, NS, BT, MS, HB), Biologix (RA), BMS/Celgene (EKH, AL), Genpharm (RA), Genzyme-Sanofi (TK, EKH, MT, GI, AL, MG, PD, PG, AVW, FG, PS, DF, RA, RH, MT, CB, JLS, EP, EP, VVP, FG, RB, RB, DS, CRT, JP, JO, MB, JLSM, SH, O Gerlach, AGK, HB), GSK (RA), Innate Immunotherapeutics (AGK), Lundbeck (EP), Merck / EMD (TK, DH, EKH, MT, GI, AL(Merck Serono), MG, PD, PG, VJ, AVW, PS, DF, RA, RH, MT, CB, JLS, EP, VVP, FG, RB, DS, RA, JO, MB, JLSM, CR, FM, O Gerlach, AGK, TC, BS, MS, HB), Mitsubishi (FG),Novartis (TK, TS, DH, EKH, MT, GI, AL, MG, PD, PG, VJ, AVW, FG, PS, DF, RA, RH, MT, CB, JLS, EP, VVP, FG, RB, DS, RA, CRT, JP, JO, MB, JLSM, SH, CR, FM, CSh, OG, AGK, TC, NS, BT, MS, HB), ONO Pharmaceuticals (FG), Roche (TK, EKH, AL, MT, CB, VVP, BT), Teva (TK, DH, EKH, MT, GI, AL, MG, PD, PG, VJ, FG, PS, DF, RH, MT, CB, JLS, VVP, RB, DS, RA, JP, JO, JLSM, CR, AGK, TC, MS, CAS), WebMD (TK), UCB (EP)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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25. Disability accrual in primary and secondary progressive multiple sclerosis.
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Harding-Forrester S, Roos I, Nguyen AL, Malpas CB, Diouf I, Moradi N, Sharmin S, Izquierdo G, Eichau S, Patti F, Horakova D, Kubala Havrdova E, Prat A, Girard M, Duquette P, Grand'Maison F, Onofrj M, Lugaresi A, Grammond P, Ozakbas S, Amato MP, Gerlach O, Sola P, Ferraro D, Buzzard K, Skibina O, Lechner-Scott J, Alroughani R, Boz C, Van Pesch V, Cartechini E, Terzi M, Maimone D, Ramo-Tello C, Yamout B, Khoury SJ, La Spitaleri D, Sa MJ, Blanco Y, Granella F, Slee M, Butler E, Sidhom Y, Gouider R, Bergamaschi R, Karabudak R, Ampapa R, Sánchez-Menoyo JL, Prevost J, Castillo-Trivino T, McCombe PA, Macdonell R, Laureys G, Van Hijfte L, Oh J, Altintas A, de Gans K, Turkoglu R, van der Walt A, Butzkueven H, Vucic S, Barnett M, Cristiano E, Hodgkinson S, Iuliano G, Kappos L, Kuhle J, Shaygannejad V, Soysal A, Weinstock-Guttman B, Van Wijmeersch B, and Kalincik T
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- Humans, Disease Progression, Proportional Hazards Models, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Disabled Persons
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Background: Some studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS., Methods: We compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS., Results: Included patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2-47.3) vs 43.9 (43.3-44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78-0.94); p<0.001) and similar age at wheelchair dependence., Conclusions: We demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials., Competing Interests: Competing interests: IR served on scientific advisory boards for Novartis and Merck, and received conference travel support and/or speaker honoraria from Roche, Novartis, Biogen, Teva, Sanofi Genzyme, and Merck. A-LN received grants from MS Research Australia; grants, personal fees, and nonfinancial support from Biogen; grants and personal fees from Merck Serono; personal fees from Teva and Novartis; and nonfinancial support from Roche and Sanofi Genzyme. GI received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall, and Teva. SE received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche, and Teva. FP received speaker honoraria and advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi Genzyme, and Teva, and research funding from Biogen, Merck, FISM (Fondazione Italiana Sclerosi Multipla), Reload Onlus Association, and the University of Catania. DH received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme, and Novartis, and support for research activities from Biogen and the Czech Ministry of Education (project PROGRES Q27/LF1). EVH received honoraria or research support from Biogen, Merck Serono, Novartis, Roche, and Teva; has been a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novartis, and Sanofi Genzyme; and received research support from the Czech Ministry of Education (project PROGRES Q27/LF1). MG received consulting fees from Teva Canada Innovation, Biogen, Novartis, and Sanofi Genzyme; lecture payments from Teva Canada Innovation, Novartis, and EMD; and research support from the Canadian Institutes of Health Research. PD served on editorial boards for, and has been supported to attend meetings by, EMD, Biogen, Novartis, Genzyme, and Teva Neuroscience; he holds grants from the Canadian Institutes of Health Research and the MS Society of Canada, and received funding for investigator-initiated trials from Biogen, Novartis, and Genzyme. FG’M received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi, and ONO Pharmaceuticals. AL received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme, and Teva; her institutions have received research grants from Novartis (in the past 4 years). PG served on advisory boards for Novartis, EMD Serono, Roche, Biogen Idec, Sanofi Genzyme, and Pendopharm; received grant support from Genzyme and Roche; and received research grants for his institution from Biogen Idec, Sanofi Genzyme, and EMD Serono. MPA received honoraria as a consultant on scientific advisory boards for Biogen, Bayer Schering, Merck, Teva, and Sanofi-Aventis, and received research grants by Biogen, Bayer Schering, Merck, Teva, and Novartis. PS served on scientific advisory boards for Biogen Idec and Teva; received funding for travel and speaker honoraria from Biogen Idec, Merck, Teva, Sanofi Genzyme, Novartis, and Bayer; and received research grants for her institution from Bayer, Biogen, Merck, Novartis, Sanofi, and Teva. DF received travel grants and/or speaker honoraria from Merck, Teva, Novartis, Biogen, and Sanofi Genzyme. KB received honoraria and consulting fees from Biogen, Teva, Novartis, Sanofi Genzyme, Roche, Merck, CSL, and Grifols. JL-S received travel compensation from Novartis, Biogen, Roche, and Merck; her institution received honoraria for talks and advisory board commitments, as well as research grants from Biogen, Merck, Roche, Teva, and Novartis. RA received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche, and Sanofi Genzyme. CB received conference travel support from Biogen, Novartis, Bayer Schering, Merck, and Teva, and participated in clinical trials by Sanofi-Aventis, Roche, and Novartis. VVP received travel grants from Merck, Biogen, Sanofi, Celgene, Almirall, and Roche; his institution received research grants and consultancy fees from Roche, Biogen, Sanofi, Celgene, Merck, and Novartis Pharma. MT received travel grants from Novartis, Bayer Schering, Merck, and Teva, and participated in clinical trials by Sanofi-Aventis, Roche, and Novartis. DM received speaker honoraria for advisory board service and travel grants from Almirall, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. CR-T received research funding, compensation for travel, or speaker honoraria from Biogen, Novartis, Genzyme, and Almirall. DLS received honoraria as a consultant on scientific advisory boards from Bayer Schering, Novartis, and Sanofi-Aventis, and compensation for travel from Novartis, Biogen, Sanofi-Aventis, Teva, and Merck. FG received an institutional research grant from Biogen and Sanofi Genzyme; served on scientific advisory boards for Biogen, Novartis, Merck, Sanofi Genzyme, and Roche; and received funding for travel and speaker honoraria from Biogen, Merck, and Sanofi-Aventis. MS participated in, but did not receive honoraria for, advisory board activity for Biogen, Merck, Bayer Schering, Sanofi-Aventis, and Novartis. RB received speaker honoraria from Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; research grants from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; and congress, travel, and accommodation expense compensations from Almirall, Bayer Schering, Biogen, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva. RA received conference travel support from Novartis, Teva, Biogen, Bayer, and Merck, and participated in clinical trials by Biogen, Novartis, Teva, and Actelion. JLS-M received travel compensation from Novartis and Biogen; received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer, and Teva; and participated in a clinical trial by Biogen. JP received travel compensation from Novartis, Biogen, Genzyme, and Teva, and speaking honoraria from Biogen, Novartis, Genzyme and Teva. TC-T received speaking or consulting fees and/or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi Genzyme, and Teva. GL received travel and/or consultancy compensation from Sanofi Genzyme, Roche, Teva, Merck, Novartis, Celgene, and Biogen. JO received research funding from the MS Society of Canada, the National MS Society, Brain Canada, Biogen Idec, Roche, and EMD Serono, and personal compensation for consulting or speaking from EMD Serono, Sanofi Genzyme, Biogen Idec, Roche, Celgene, and Novartis. AA received personal fees and speaker honoraria from Teva, Merck, Biogen Gen Pharma, Roche, Novartis, Bayer, and Sanofi Genzyme, and received travel and registration grants from Merck, Biogen Gen Pharma, Roche, Sanofi Genzyme, and Bayer. HB received compensation for consulting, talks, and advisory or steering board activities from Biogen, Merck, Novartis, Genzyme, Alfred Health, and Oxford Health Policy Forum, and research support from Novartis, Biogen, Roche, Merck, the National Health and Medical Research Council of Australia, Pennycook Foundation, and MS Research Australia MB served on scientific advisory boards for Biogen, Novartis, and Genzyme, received conference travel support from Biogen and Novartis, and serves on steering committees for trials conducted by Novartis; his institution received research support from Biogen, Merck, and Novartis. EC Cristiano received honoraria as a consultant on scientific advisory boards for Biogen, Bayer Schering, Merck, Genzyme, and Novartis, and participated in clinical trials or other research projects by Merck, Roche, and Novartis. SH received honoraria and consulting fees from Novartis, Bayer Schering, and Sanofi, and travel grants from Novartis, Biogen Idec, and Bayer Schering. GI received compensation for travel, accommodations, and meeting expenses from Bayer Schering, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva. LK received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen, Elan, European Union, Genmab, Gianni Rubatto Foundation, GlaxoSmithKline, Glenmark, MediciNova, Merck, Novartis, Novartis Research Foundation, Roche, Roche Research Foundation, Sanofi-Aventis, Santhera, the Swiss MS Society, the Swiss National Research Foundation, Teva Neuroscience, UCB, and Wyeth. BW-G participated in speakers' bureaus and/or served as a consultant for Biogen, EMD Serono, Novartis, Genentech, Celgene/Bristol Meyers Squibb, Sanofi Genzyme, Bayer, Janssen, and Horizon; received grant/research support from these same agencies; and serves on editorial boards for BMJ Neurology, Children, CNS Drugs, MS International, and Frontiers Epidemiology. BVW received research and travel grants and honoraria for advisory and speaking fees from Bayer Schering, Biogen, Sanofi Genzyme, Merck, Novartis, Roche, and Teva. TK served on scientific advisory boards for BMS, Roche, Sanofi Genzyme, Novartis, Merck, and Biogen, and the steering committee for the Brain Atrophy Initiative by Sanofi Genzyme; received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi Genzyme, Teva, BioCSL, and Merck; and received support for research or educational events from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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26. Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network.
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Signori A, Lorscheider J, Vukusic S, Trojano M, Iaffaldano P, Hillert J, Hyde R, Pellegrini F, Magyari M, Koch-Henriksen N, Sørensen PS, Spelman T, van der Walt A, Horakova D, Havrdova E, Girard M, Eichau S, Grand'Maison F, Gerlach O, Terzi M, Ozakbas S, Skibina O, Van Pesch V, Sa MJ, Prevost J, Alroughani R, McCombe PA, Gouider R, Mrabet S, Castillo-Trivino T, Zhu C, de Gans K, Sánchez-Menoyo JL, Yamout B, Khoury S, Sormani MP, Kalincik T, and Butzkueven H
- Subjects
- Humans, Latent Class Analysis, Disease Progression, Registries, Multiple Sclerosis, Chronic Progressive drug therapy, Disabled Persons, Multiple Sclerosis drug therapy
- Abstract
Background: Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time., Methods: All patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3-4., Results: A total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria., Conclusions: Contrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression., Competing Interests: Competing interests: AS received research support from MSBase. JL received research support from Innosuisse—Swiss Innovation Agency, Biogen and Novartis; he served on advisory boards for Biogen, Novartis, Roche and Teva. SV received consulting and lecture fees, travel grants and research support from Biogen, Celgene, Genentech, Genzyme, Medday Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Aventis and Teva Pharma. MT has served on scientific advisory boards for Biogen, Novartis, Roche and Genzyme; has received speaker honoraria and travel support from Biogen Idec, Sanofi-Aventis, Merck Serono, Teva, Genzyme and Novartis; and has received research grants for her institution from Biogen Idec, Merck Serono and Novartis. JH has received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme and Novartis; and speaker’s fees from Biogen, Novartis, Merck Serono, Bayer-Schering, Teva and Sanofi-Genzyme. He has served as PI for projects or received unrestricted research support from Biogen Idec, Merck Serono, TEVA, Sanofi-Genzyme and Bayer-Schering; his MS research is funded by the Swedish Research Council and the Swedish Brain Foundation. RH is an employee of Biogen and holds a stock. FP is an employee of Biogen. MM has served on scientific advisory board for Biogen Idec and Teva; and has received honoraria for lecturing from Biogen Idec, Merck Serono, Sanofi-Aventis and Teva. NK-H has received honoraria for lecturing and participating in advisory councils, travel expenses for attending congresses and meetings, and financial support for monitoring the Danish Multiple Sclerosis Treatment Register from Bayer-Schering, Merck Serono, Biogen Idec, Teva, Sanofi-Aventis and Novartis. PSS has served on scientific advisory boards for Merck Serono, Teva, Novartis, Sanofi-Aventis and Biogen Idec; has received research support from Biogen Idec, Novartis and Sanofi-Aventis; and received speaker honoraria from Merck Serono, Novartis, Teva, Sanofi-Aventis, Biogen Idec and Genzyme. TS received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen; and speaker honoraria from Novartis. AvdW reported receiving grants from National Health and Medical Research Council (NHMRC), Novartis, Roche and MS Research Australia; and personal fees from Biogen, Merck, Novartis and Roche. DH received compensation for travel, speaker honoraria and consultant fees from Biogen, Novartis, Merck Healthcare (Darmstadt, Germany), Bayer, Sanofi, Roche and Teva, as well as support for research activities from Biogen. She was also supported by the Charles University: Cooperation Program in neuroscience. EH received honoraria/research support from Biogen, Merck Serono, Novars, Roche and Teva; has been a member of advisory boards for Actelion, Biogen, Celgene, Merck Serono, Novars and Sanofi Genzyme. MG received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; and lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research. SE received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. FG received honoraria or research funding from Biogen, Genzyme, Novartis, Teva Neurosciences, Mitsubishi and ONO Pharmaceuticals. OG has nothing to disclose. MT received travel grants from Novartis, Bayer-Schering, Merck and Teva; and has participated in clinical trials by Sanofi Aventis, Roche and Novartis. SO has nothing to disclose. OS has received honoraria and consulting fees from Bayer Schering, Novartis, Merck, Biogen and Genzyme companies. VVP received travel grants from Merck Healthcare (Darmstadt, Germany), Biogen, Sanofi, Bristol Meyer Squibb, Almirall and Roche. His institution has received research grants and consultancy fees from Roche, Biogen, Sanofi, Merck Healthcare (Darmstadt, Germany), Bristol Meyer Squibb, Janssen, Almirall and Novartis Pharma. MJS received consulting fees, speaker honoraria, and/or travel expenses for scientific meetings from Alexion, Bayer Healthcare, Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck-Serono, Novartis, Roche, Sanofi and Teva. JP accepted travel compensation from Novartis, Biogen, Genzyme and Teva; and speaking honoraria from Biogen, Novartis, Genzyme and Teva. RA received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. PAM received speakers fees and travel grants from Novartis, Biogen, T’évalua and Sanofi. RG has nothing to disclose. SM has received a MENACTRIMS clinical fellowship grant (2020). TC-T received speaking/consulting fees and/or travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. CZ has nothing to disclose. KdG has nothing to disclose. JLS-M accepted travel compensation from Novartis, Merck and Biogen; speaking honoraria from Biogen, Novartis, Sanofi, Merck, Almirall, Bayer and Teva; and has participated in clinical trials by Biogen, Merck and Roche. BY and SK have nothing to disclose. MPS has received consulting fees from Biogen, Merck, Teva, Genzyme, Roche, Novartis, GeNeuro and MedDay. TK reported receiving grants from MS Research Australia and grants, personal fees and non-financial support from Biogen; personal fees and non-financial support from Sanofi Genzyme and Merck; personal fees from Roche, Novartis, WebMD Global, Teva and BioCSL; and grants from NHMRC, MS Research Australia, ARSEP-OFSEP, UK MS Society and Medical Research Future Fund. HB’s institution (Monash University) received compensation for consulting, talks, and advisory/steering board activities from Alfred Health, Biogen, Merck, Novartis, Roche and UCB pharma; research support from Biogen, Merck, Roche, MS Australia, National Health and Medical Research (Australia) and the Medical Research Future Fund (Australia), the Pennycook Foundation, Novartis and Roche. He has received personal compensation for steering group activities from Oxford Health Policy Forum., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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27. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis.
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Roos I, Malpas C, Leray E, Casey R, Horakova D, Havrdova EK, Debouverie M, Patti F, De Seze J, Izquierdo G, Eichau S, Edan G, Prat A, Girard M, Ozakbas S, Grammond P, Zephir H, Ciron J, Maillart E, Moreau T, Amato MP, Labauge P, Alroughani R, Buzzard K, Skibina O, Terzi M, Laplaud DA, Berger E, Grand'Maison F, Lebrun-Frenay C, Cartechini E, Boz C, Lechner-Scott J, Clavelou P, Stankoff B, Prevost J, Kappos L, Pelletier J, Shaygannejad V, Yamout BI, Khoury SJ, Gerlach O, Spitaleri DLA, Van Pesch V, Gout O, Turkoglu R, Heinzlef O, Thouvenot E, McCombe PA, Soysal A, Bourre B, Slee M, Castillo-Trivino T, Bakchine S, Ampapa R, Butler EG, Wahab A, Macdonell RA, Aguera-Morales E, Cabre P, Ben NH, Van der Walt A, Laureys G, Van Hijfte L, Ramo-Tello CM, Maubeuge N, Hodgkinson S, Sánchez-Menoyo JL, Barnett MH, Labeyrie C, Vucic S, Sidhom Y, Gouider R, Csepany T, Sotoca J, de Gans K, Al-Asmi A, Fragoso YD, Vukusic S, Butzkueven H, and Kalincik T
- Subjects
- Humans, Female, Natalizumab therapeutic use, Fingolimod Hydrochloride therapeutic use, Retrospective Studies, Recurrence, Immunosuppressive Agents adverse effects, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Multiple Sclerosis chemically induced
- Abstract
Background and Objectives: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy., Methods: This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation., Results: A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80)., Discussion: The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different therapies. These results suggest that untreated intervals should be minimized after stopping antitrafficking therapies (natalizumab and fingolimod)., Classification of Evidence: This study provides Class III that disease reactivation occurs within months of discontinuation of MS disease-modifying therapies. The risk of disease activity is reduced by commencement of a subsequent therapy., (© 2022 American Academy of Neurology.)
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- 2022
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28. Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis.
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Yeh WZ, Widyastuti PA, Van der Walt A, Stankovich J, Havrdova E, Horakova D, Vodehnalova K, Ozakbas S, Eichau S, Duquette P, Kalincik T, Patti F, Boz C, Terzi M, Yamout BI, Lechner-Scott J, Sola P, Skibina OG, Barnett M, Onofrj M, Sá MJ, McCombe PA, Grammond P, Ampapa R, Grand'Maison F, Bergamaschi R, Spitaleri DLA, Van Pesch V, Cartechini E, Hodgkinson S, Soysal A, Saiz A, Gresle M, Uher T, Maimone D, Turkoglu R, Hupperts RM, Amato MP, Granella F, Oreja-Guevara C, Altintas A, Macdonell RA, Castillo-Trivino T, Butzkueven H, Alroughani R, and Jokubaitis VG
- Abstract
Objective: To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort., Methods: Using data from the MSBase Registry, we included pregnancies conceived after 31 Dec 2010 from women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse, and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses., Results: We included 1998 pregnancies from 1619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% CI 0.27-0.32), fell to 0.19 (0.14-0.24) in third trimester, and increased to 0.59 (0.51-0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28-0.49) and 0.29 (0.22-0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p<0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41-0.91], p=0.016). 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum., Conclusion: Intrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation, with early re-initiation after delivery is an effective option to minimize relapse risks. Strategies of DMT use have to be balanced against potential fetal/neonatal complications., (© 2021 American Academy of Neurology.)
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- 2021
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29. O group is a protective factor for COVID19 in Basque population.
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Muñoz-Culla M, Roncancio-Clavijo A, Martínez B, Gorostidi-Aicua M, Piñeiro L, Azkune A, Alberro A, Monge-Ruiz J, Castillo-Trivino T, Prada A, and Otaegui D
- Subjects
- Aged, COVID-19 blood, COVID-19 prevention & control, Humans, Middle Aged, Protective Factors, Spain ethnology, ABO Blood-Group System, Blood Donors classification, COVID-19 epidemiology
- Abstract
ABO blood groups have recently been related to COVID19 infection. In the present work, we performed this analysis using data from 412 COVID19 patients and 17796 blood donors, all of them from Gipuzkoa, a region in Northern Spain. The results obtained confirmed this relation, in addition to showing a clear importance of group O as a protective factor in COVID19 disease, with an OR = 0.59 (CI95% 0.481-0.7177, p<0.0001) while A, B and AB are risk factors. ABO blood groups are slightly differently distributed in the populations and therefore these results should be replicated in the specific areas with a proper control population., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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30. [Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Navarra, Gipuzkoa and La Rioja].
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Ayuso T, Marzo-Sola ME, Castillo-Trivino T, Soriano G, Otano MA, Lopez MA, Croitoru IM, and Olascoaga J
- Abstract
Aim: To evaluate the effectiveness and safety of fingolimod in clinical practice in Navarra, Gipuzkoa and La Rioja regions., Patients and Methods: We conducted a retrospective multi-centre study with recurrent multiple sclerosis patients treated with fingolimod, following the product data sheet. The following data were evaluated: annualised relapse rate (ARR), percentage of patients free from relapses, disability using the Expanded Disability Status Scale (EDSS) and the percentage of patients without gadolinium-enhancing lesions., Results: A total of 113 patients were treated with fingolimod: 6% were naive, and 58% and 35% were patients previously treated with an immunomodulator and natalizumab, respectively. Fingolimod lowered the ARR after the first (67%; 1 to 0.3; p < 0.0001) and second (89%; 1 to 0.1; p < 0.0001) years of treatment, and thus the number of patients free from relapses during the treatment increased. The baseline EDSS was 3 and after treatment with fingolimod was 2.5 in both years. The percentage of patients without gadolinium-enhancing lesions after the first year of treatment was 77%. Similar results were observed in naive patients and in those previously treated with an immunomodulator. In patients previously treated with natalizumab no changes were observed following the treatment., Conclusions: The use of fingolimod in clinical practice showed an effectiveness similar to that observed in clinical trials. There were no changes in the ARR after changing from natalizumab, and only one patient presented a 'relapse' after withdrawal of natalizumab. Fingolimod acts like a safe drug, with scarce side effects and a low percentage of drop-outs.
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- 2016
31. Ventricular tachycardia on chronic fingolimod treatment for multiple sclerosis.
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Castillo-Trivino T, Lopetegui I, Alarcón-Duque JA, López de Munain A, and Olascoaga J
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- Adult, Electrocardiography, Ambulatory, Female, Fingolimod Hydrochloride, Humans, Immunosuppressive Agents therapeutic use, Propylene Glycols therapeutic use, Sphingosine adverse effects, Sphingosine therapeutic use, Immunosuppressive Agents adverse effects, Multiple Sclerosis drug therapy, Propylene Glycols adverse effects, Sphingosine analogs & derivatives, Tachycardia, Ventricular chemically induced
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- 2015
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32. Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review.
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Castillo-Trivino T, Braithwaite D, Bacchetti P, and Waubant E
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- Adolescent, Adult, Aged, Central Nervous System immunology, Central Nervous System pathology, Clinical Trials as Topic, Databases, Bibliographic, Humans, Middle Aged, Multiple Sclerosis, Chronic Progressive immunology, Multiple Sclerosis, Chronic Progressive pathology, Multiple Sclerosis, Relapsing-Remitting immunology, Multiple Sclerosis, Relapsing-Remitting pathology, Rituximab, Treatment Outcome, Antibodies, Monoclonal, Murine-Derived therapeutic use, Central Nervous System drug effects, Immunologic Factors therapeutic use, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy
- Abstract
Background: Rituximab is an anti-CD20 monoclonal antibody approved for non Hodgkin lymphoma and rheumatoid arthritis. It is being considered for the treatment of MS., Objectives: To evaluate the efficacy and safety of rituximab for MS treatment., Data Collection: Studies were selected if they were clinical trials, irrespective of the dosage or combination therapies., Main Results: Four studies with a total of 599 patients were included. One assessed the efficacy of rituximab for primary progressive (PP) MS while the other three focused on relapsing-remitting (RR) MS. In the PPMS study, rituximab delayed time to confirmed disease progression (CDP) in pre-planned sub-group analyses. The increase in T2 lesion volume was lower in the rituximab group at week 96 compared with placebo. For the RRMS studies, an open-label phase I study found that rituximab reduced the annualized relapse rate to 0.25 from pre-therapy baseline to week 24, while in the randomized placebo-controlled phase II trial, annualized relapse rates were 0.37 in the rituximab group and 0.84 in the placebo group (p = 0.04) at week 24. Rituximab dramatically reduced the number of gadolinium-enhancing lesions on brain MRI scans for both RRMS studies. Off-label rituximab as an add-on therapy in patients with breakthrough disease on first-line agents was associated with an 88% reduction when comparing the mean number of gadolinium-enhancing lesions prior to and after the treatment. Although frequent adverse events classified as mild or moderate occurred in up to 77% of the patients, there were no grade 4 infusion-related adverse events. AUTHOR’S CONCLUSION: Despite the frequent mild/moderate adverse events related to the drug, rituximab appears overall safe for up to 2 years of therapy and has a substantial impact on the inflammatory disease activity (clinical and/or radiological) of RRMS. The effect of rituximab on disease progression in PPMS appears to be marginal.
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- 2013
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33. Clinical response to thalidomide in the treatment of intracranial tuberculomas: case report.
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de la Riva P, Urtasun M, Castillo-Trivino T, Camino X, Arruti M, Mondragón E, and Lopez de Munain A
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- Adult, Clinical Trials as Topic methods, Clinical Trials as Topic trends, Female, Humans, Treatment Outcome, Antitubercular Agents therapeutic use, Thalidomide therapeutic use, Tuberculoma, Intracranial diagnosis, Tuberculoma, Intracranial drug therapy
- Abstract
We describe a patient with multiple intracranial tuberculomas resistant to standard care with antituberculosis drugs and corticosteroids who responded well to thalidomide. Adjunctive thalidomide may have a role in the management of refractory intracranial tuberculomas, although it should be used conservatively owing to its potential adverse events.
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- 2013
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34. Switching multiple sclerosis patients with breakthrough disease to second-line therapy.
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Castillo-Trivino T, Mowry EM, Gajofatto A, Chabas D, Crabtree-Hartman E, Cree BA, Goodin DS, Green AJ, Okuda DT, Pelletier D, Zamvil SS, Vittinghoff E, and Waubant E
- Subjects
- Adult, Algorithms, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Chemotherapy, Adjuvant, Cohort Studies, Disease Progression, Female, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting pathology, Natalizumab, Recurrence, Retrospective Studies, Drug Substitution methods, Immunologic Factors therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
- Abstract
Background: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown., Methods: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch., Results: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004)., Conclusions: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.
- Published
- 2011
- Full Text
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