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1. Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study

Author: Nguyen, Ai-Lan, Havrdova, Eva Kubala, Horakova, Dana, Izquierdo, Guillermo, Kalincik, Tomas, van der Walt, Anneke, Terzi, Murat, Alroughani, Raed, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Boz, Cavit, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Lechner-Scott, Jeannette, Barnett, Michael, Grand'Maison, Francois, Grammond, Pierre, Ramo-Tello, Cristina, Turkoglu, Recai, McCombe, Pamela, Pucci, Eugenio, Trojano, Maria, Granella, Franco, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Oreja-Guevara, Celia, Verheul, Freek, Vucic, Steve, Hodgkinson, Suzanne, Slee, Mark, Ampapa, Radek, Prevost, Julie, Menoyo, Jose Luis Sanchez, Skibina, Olga, Solaro, Claudio, Olascoaga, Javier, Shaw, Cameron, Madsen, Klaus Gregaard, Naidoo, Kerisha, Hyde, Robert, Butzkueven, Helmut, and Jokubaitis, Vilija
Published: 2019
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2. Lymphocyte count in peripheral blood is not associated with the level of clinical response to treatment with fingolimod

Author: Fragoso, Yara Dadalti, Spelman, Tim, Boz, Cavit, Alroughani, Raed, Lugaresi, Alessandra, Vucic, Steve, Butzkueven, Helmut, Terzi, Murat, Havrdova, Eva, Horakova, Dana, Granella, Franco, Olascoaga, Javier, Sánchez-Menoyo, José Luis, Pucci, Eugenio, Barnett, Michael, Brooks, Joseph Bruno B., and Haartsen, Jodi
Published: 2018
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3. Effect of Disease Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years

Author: Kalincik, Tomas, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charles, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, GrandʼMaison, Francois, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Luis, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, and Butzkueven, Helmut
Published: 2020
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4. Different clinical response to interferon beta and glatiramer acetate related to the presence of oligoclonal IgM bands in CSF in multiple sclerosis patients

Author: Casanova, Bonaventura, Lacruz, Laura, Villar, María Luisa, Domínguez, José Andrés, Gadea, María Carcelén, Gascón, Francisco, Mallada, Javier, Hervás, David, Simó-Castelló, María, Álvarez-Cermeño, José Carlos, Calles, Carmen, Olascoaga, Javier, Ramió-Torrentà, Lluís, Alcalá, Carmen, Cervelló, Angeles, Boscá, Isabel, Pérez-Mirallles, Francisco Carlos, and Coret, Francisco
Published: 2018
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5. Comparison of 2-year Teriflunomide Outcomes between DMT-naive and switch patients with Relapsing MS: subanalysis of the Real-World TERICARE study (P6-3.003)

Author: Lallana, Jose Meca, primary, Prieto, Jose María, additional, Caminero, Ana Belén, additional, Olascoaga, Javier, additional, Portell, Rosa Casademont, additional, and Forner, Mireia, additional
Published: 2023
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6. Comparative effectiveness of autologous hematopoietic stem cell transplant vs Fingolimod, Natalizumab, and Ocrelizumab in highly active relapsing-remitting multiple sclerosis

Author: Kalincik, Tomas, Sharmin, Sifat, Roos, Izanne, Freedman, Mark S., Atkins, Harold, Burman, Joachim, Massey, Jennifer, Sutton, Ian, Withers, Barbara, Macdonell, Richard, Grigg, Andrew, Torkildsen, Øivind, Bo, Lars, Lehmann, Anne Kristine, Havrdova, Eva Kubala, Krasulova, Eva, Trněný, Marek, Kozak, Tomas, van der Walt, Anneke, Butzkueven, Helmut, McCombe, Pamela, Skibina, Olga, Lechner-Scott, Jeannette, Willekens, Barbara, Cartechini, Elisabetta, Ozakbas, Serkan, Alroughani, Raed, Kuhle, Jens, Patti, Francesco, Duquette, Pierre, Lugaresi, Alessandra, Khoury, Samia J., Slee, Mark, Turkoglu, Recai, Hodgkinson, Suzanne, John, Nevin, Maimone, Davide, Sa, Maria Jose, van Pesch, Vincent, Gerlach, Oliver, Laureys, Guy, Van Hijfte, Liesbeth, Karabudak, Rana, Spitaleri, Daniele, Csepany, Tunde, Gouider, Riadh, Castillo-Triviño, Tamara, Taylor, Bruce, Sharrack, Basil, Snowden, John A., Horakova, Dana, Buzzard, Katherine, Terzi, Murat, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Barnett, Michael, Stewart, Grace, Onofrj, Marco, Izquierdo, Guillermo, Eichau, Sara, Grand'Maison, Francois, Prevost, Julie, Van Wijmeersch, Bart, Amato, Maria Pia, Shaygannejad, Vahid, Boz, Cavit, Bolaños, Ricardo Fernandez, Soysal, Aysun, Ramo-Tello, Cristina, Solaro, Claudio, Gobbi, Claudio, Cabrera-Gomez, Jose Antonio, Roullet, Etienne, Zwanikken, Cees, Den braber-Moerland, Leontien, Deri, Norma, Saladino, Maria Laura, Cristiano, Edgardo, Rojas, Juan Ignacio, Vrech, Carlos, Shaw, Cameron, Shuey, Neil, Boggild, Mike, Tan, Ik Lin, Hardy, Todd, Decoo, Danny, Moore, Fraser, Oh, Jiwon, Lalive, Patrice, Ampapa, Radek, Petersen, Thor, Oreja-Guevara, Celia, Perez Sempere, Angel, Dominguez, Jose Andres, Besora, Sarah, Hughes, Stella, Gray, Orla, Grigoriadis, Nikolaos, Piroska, Imre, Rozsa, Csilla, Kasa, Krisztian, Simo, Magdolna, Kovacs, Krisztina, Sas, Attila, Dobos, Eniko, Rajda, Cecilia, McGuigan, Chris, Mason, Deborah, Schepel, Jan, Alkhaboori, Jabir, Rio, Maria Edite, Mihaela, Simu, Al-Harbi, Talal, Altintas, Ayse, Kister, Ilya, Marriott, Mark, Kilpatrick, Trevor, King, John, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Taylor, Lisa, Diamanti, Matteo, Chisari, Clara, Toscano, Simona, Salvatore, Lo Fermo, Larochelle, Catherine, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Hupperts, Raymond, Olascoaga, Javier, Saiz, Albert, Zivadinov, Robert, Benedict, Ralph, Verheul, Freek, Fabis-Pedrini, Marzena, Mrabet, Saloua, Garber, Justin, Sanchez-Menoyo, Jose Luis, Aguera-Morales, Eduardo, Blanco, Yolanda, Al-Asmi, Abdullah, Weinstock-Guttman, Bianca, Fragoso, Yara, de Gans, Koen, and Kermode, Allan
Subjects: Human medicine
Abstract: you are agreeing to our Cookie Policy | Continue JAMA Network HomeJAMA Neurology This Issue Views 2,357 Citations 0 60 Full Text Share Comment Original Investigation May 15, 2023 Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis Tomas Kalincik, MD, PhD1,2; Sifat Sharmin, PhD1,2; Izanne Roos, MBChB, PhD1,2; Mark S. Freedman, MD3; Harold Atkins, MD4; Joachim Burman, MD, PhD5; Jennifer Massey, MBBS, PhD6,7; Ian Sutton, MBBS, PhD6,8; Barbara Withers, MD, PhD7,9; Richard Macdonell, MD, PhD10,11; Andrew Grigg, MD, PhD11,12; Øivind Torkildsen, MD, PhD13; Lars Bo, MD, PhD13; Anne Kristine Lehmann, MD, PhD14; Eva Kubala Havrdova, MD, PhD15; Eva Krasulova, MD, PhD15; Marek Trněný, MD, PhD16; Tomas Kozak, MD, PhD17; Anneke van der Walt, MBBS, PhD18,19; Helmut Butzkueven, MBBS, PhD18,19; Pamela McCombe, MBBS20,21; Olga Skibina, MBBS18,22,23; Jeannette Lechner-Scott, MD, PhD24,25; Barbara Willekens, MD, PhD26,27; Elisabetta Cartechini, MD28; Serkan Ozakbas, MD29; Raed Alroughani, MD30; Jens Kuhle, MD, PhD31; Francesco Patti, MD32,33; Pierre Duquette, MD34; Alessandra Lugaresi, MD, PhD35,36; Samia J. Khoury, MD, PhD37; Mark Slee, MD, PhD38; Recai Turkoglu, MD39; Suzanne Hodgkinson, MD40; Nevin John, MD, PhD41,42; Davide Maimone, MD43; Maria Jose Sa, MD44; Vincent van Pesch, MD, PhD45,46; Oliver Gerlach, MD, PhD47,48; Guy Laureys, MD49; Liesbeth Van Hijfte, MD49; Rana Karabudak, MD50; Daniele Spitaleri, MD51; Tunde Csepany, MD, PhD52; Riadh Gouider, MD53,54; Tamara Castillo-Triviño, MD55; Bruce Taylor, MD, PhD56,57; Basil Sharrack, MD, PhD58; John A. Snowden, MD, PhD59; and the MSBase Study Group Collaborators; and the MSBase Study Group Authors Author Affiliations JAMA Neurol. 2023;80(7):702-713. doi:10.1001/jamaneurol.2023.1184 editorial comment iconEditorial Comment Key Points Question What is the comparative effectiveness of autologous hematopoietic stem cell transplant (AHSCT) vs individual most potent disease-modifying therapies for relapsing-remitting multiple sclerosis (MS), such as natalizumab or ocrelizumab? Findings In this observational comparative effectiveness study of 4915 individuals using a composite cohort from specialized MS centers and the MSBase international registry, the effectiveness of AHSCT was compared with 1 medium-efficacy and 2 high-efficacy disease-modifying therapies (fingolimod, natalizumab, and ocrelizumab) in patients with relapsing-remitting MS, high frequency of relapses, and moderate disability. Over 5 years, AHSCT was associated with substantially lower relapse rate than fingolimod and marginally lower relapse rate than natalizumab and was also associated with a higher rate of recovery from disability compared with fingolimod and natalizumab, but no evidence of difference in clinical outcomes between AHSCT and ocrelizumab was found at 3-year follow-up. Meaning The results indicate that in relapsing-remitting MS, the clinical effectiveness of AHSCT is considerably superior to fingolimod and marginally superior to natalizumab. Abstract Importance Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time.
Published: 2023

7. Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis

Author: Iparraguirre, Leire, Muñoz-Culla, Maider, Prada-Luengo, Iñigo, Castillo-Triviño, Tamara, Olascoaga, Javier, and Otaegui, David
Published: 2017
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8. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response

Author: Kalincik, Tomas, Manouchehrinia, Ali, Sobisek, Lukas, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Grammond, Pierre, Sola, Patrizia, Hupperts, Raymond, GrandʼMaison, Francois, Pucci, Eugenio, Boz, Cavit, Alroughani, Raed, Van Pesch, Vincent, Lechner-Scott, Jeannette, Terzi, Murat, Bergamaschi, Roberto, Iuliano, Gerardo, Granella, Franco, Spitaleri, Daniele, Shaygannejad, Vahid, Oreja-Guevara, Celia, Slee, Mark, Ampapa, Radek, Verheul, Freek, McCombe, Pamela, Olascoaga, Javier, Amato, Maria Pia, Vucic, Steve, Hodgkinson, Suzanne, Ramo-Tello, Cristina, Flechter, Shlomo, Cristiano, Edgardo, Rozsa, Csilla, Moore, Fraser, Sanchez-Menoyo, Jose Luis, Saladino, Maria Laura, Barnett, Michael, Hillert, Jan, and Butzkueven, Helmut
Published: 2017
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9. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis

Author: Lizak, Nathaniel, Lugaresi, Alessandra, Alroughani, Raed, Lechner-Scott, Jeannette, Slee, Mark, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Grammond, Pierre, Hupperts, Raymond, GrandʼMaison, Francois, Sola, Patrizia, Pucci, Eugenio, Bergamaschi, Roberto, Oreja-Guevara, Celia, Van Pesch, Vincent, Ramo, Cristina, Spitaleri, Daniele, Iuliano, Gerardo, Boz, Cavit, Granella, Franco, Olascoaga, Javier, Verheul, Freek, Rozsa, Csilla, Cristiano, Edgardo, Flechter, Shlomo, Hodgkinson, Suzanne, Amato, Maria Pia, Deri, Norma, Jokubaitis, Vilija, Spelman, Tim, Butzkueven, Helmut, and Kalincik, Tomas
Published: 2017
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10. Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study

Author: Vitkova, Marianna, Diouf, Ibrahima, Malpas, Charles, Horakova, Dana, Kubala Havrdova, Eva, Patti, Francesco, Ozakbas, Serkan, Izquierdo, Guillermo, Eichau, Sara, Shaygannejad, Vahid, Onofrj, Marco, Lugaresi, Alessandra, Alroughani, Raed, Prat, Alexandre, Larochelle, Catherine, Girard, Marc, Duquette, Pierre, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Grammond, Pierre, Butzkueven, Helmut, Buzzard, Katherine, Skibina, Olga, Yamout, Bassem I, Karabudak, Rana, Gerlach, Oliver, Lechner-Scott, Jeannette, Maimone, Davide, Bergamaschi, Roberto, Van Pesch, Vincent, Iuliano, Gerardo, Cartechini, Elisabetta, José Sà, Maria, Ampapa, Radek, Barnett, Michael, Hughes, Stella E, Ramo-Tello, Cristina M, Hodgkinson, Suzanne, Spitaleri, Daniele L A, Petersen, Thor, Butler, Ernest Gerard, Slee, Mark, McGuigan, Chris, McCombe, Pamela Ann, Granella, Franco, Cristiano, Edgardo, Prevost, Julie, Taylor, Bruce V, Sãnchez-Menoyo, Josã Luis, Laureys, Guy, Van Hijfte, Liesbeth, Vucic, Steve, Macdonell, Richard A, Gray, Orla, Olascoaga, Javier, Deri, Norma, Fragoso, Yara Dadalti, Shaw, Cameron, Kalincik, Tomas, MSBase Study Group, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Subjects: Male, Disability Evaluation, Multiple Sclerosis, Ultraviolet Rays, Sunlight, Humans, Female, Neurology (clinical), Registries, Severity of Illness Index, Research Article
Abstract: Background and ObjectivesThe severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS.MethodsThis observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration’s Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS.ResultsThe 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35′ and 56°16′) were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes DiscussionIn temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.
Published: 2022

11. Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years

Author: Kalincik, Tomas, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charles, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Luis, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, Butzkueven, Helmut, MSBase Study Group, UCL - (SLuc) Service de neurologie, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Kalincik, Toma, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charle, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francoi, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Lui, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, and Butzkueven, Helmut
Subjects: Adult, Male, medicine.medical_specialty, Article, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, multiple sclerosis, treatment, prognosis, Internal medicine, medicine, Humans, Immunologic Factors, Disease Progression, Female, Fingolimod Hydrochloride, Glatiramer Acetate, Immunosuppressive Agents, Interferon-beta, Longitudinal Studies, Middle Aged, Proportional Hazards Models, 030212 general & internal medicine, Glatiramer acetate, Expanded Disability Status Scale, Proportional hazards model, business.industry, Multiple sclerosis, Hazard ratio, medicine.disease, Confidence interval, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: ObjectiveTo test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.MethodsWe studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.ResultsA total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43–0.82, p = 0.0016), worsening of disability (0.56, 0.38–0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19–0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p = 10−9) and worsening of disability (0.81, 0.67–0.99, p = 0.043).ConclusionContinued treatment with MS immunotherapies reduces disability accrual by 19%–44% (95% CI 1%–62%), the risk of need of a walking aid by 67% (95% CI 41%–81%), and the frequency of relapses by 40–41% (95% CI 18%–57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.Classification of EvidenceThis study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
Published: 2021

12. Age gene expression and coexpression progressive signatures in peripheral blood leukocytes

Author: Irizar, Haritz, Goñi, Joaquín, Alzualde, Ainhoa, Castillo-Triviño, Tamara, Olascoaga, Javier, Lopez de Munain, Adolfo, and Otaegui, David
Published: 2015
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13. Validation of the CD6 and TNFRSF1A loci as risk factors for multiple sclerosis in Spain

Author: Swaminathan, Bhairavi, Matesanz, Fuencisla, Cavanillas, Mariá L., Alloza, Iraide, Otaegui, David, Olascoaga, Javier, Cénit, María C., Heras, Virgina de las, Barcina, María García, Arroyo, Rafael, Alcina, Antonio, Fernandez, Oscar, Antigüedad, Alfredo, Urcelay, Elena, and Vandenbroeck, Koen
Published: 2010
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14. A functional variant that affects exon-skipping and protein expression of SP140 as genetic mechanism predisposing to multiple sclerosis

Author: Matesanz, Fuencisla, Potenciano, Victor, Fedetz, Maria, Ramos-Mozo, Priscila, Abad-Grau, María del Mar, Karaky, Mohamad, Barrionuevo, Cristina, Izquierdo, Guillermo, Ruiz-Peña, Juan Luis, García-Sánchez, María Isabel, Lucas, Miguel, Fernández, Óscar, Leyva, Laura, Otaegui, David, Muñoz-Culla, Maider, Olascoaga, Javier, Vandenbroeck, Koen, Alloza, Iraide, Astobiza, Ianire, Antigüedad, Alfredo, Villar, Luisa María, Álvarez-Cermeño, José Carlos, Malhotra, Sunny, Comabella, Manuel, Montalban, Xavier, Saiz, Albert, Blanco, Yolanda, Arroyo, Rafael, Varadé, Jezabel, Urcelay, Elena, and Alcina, Antonio
Published: 2015
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15. Ventricular tachycardia on chronic fingolimod treatment for multiple sclerosis

Author: Castillo-Trivino, Tamara, Lopetegui, Itziar, Alarcón-Duque, Jose Antonio, López de Munain, Adolfo, and Olascoaga, Javier
Published: 2015
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16. Lipid-specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab

Author: Villar, Luisa M., Costa-Frossard, Lucienne, Masterman, Thomas, Fernandez, Oscar, Montalban, Xavier, Casanova, Bonaventura, Izquierdo, Guillermo, Coret, Francisco, Tumani, Hayrettin, Saiz, Albert, Arroyo, Rafael, Fink, Katharina, Leyva, Laura, Espejo, Carmen, Simó-Castelló, María, García-Sánchez, María I., Lauda, Florian, Llufriú, Sara, Álvarez-Lafuente, Roberto, Olascoaga, Javier, Prada, Alvaro, Oterino, Agustín, de Andrés, Clara, Tintoré, Mar, Ramió-Torrentà, Lluis, Rodríguez-Martín, Eulalia, Picón, Carmen, Comabella, Manuel, Quintana, Ester, Agüera, Eduardo, Díaz, Santiago, Fernandez-Bolaños, Ricardo, García-Merino, Juan A., Landete, Lamberto, Menéndez-González, Manuel, Navarro, Laura, Pérez, Domingo, Sánchez-López, Fernando, Serrano-Castro, Pedro J., Tuñón, Alberto, Espiño, Mercedes, Muriel, Alfonso, Bar-Or, Amit, and Álvarez-Cermeño, José C.
Published: 2015
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17. Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Author: UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Kalincik, Tomas, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charles, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Luis, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, Butzkueven, Helmut, MSBase Study Group, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Kalincik, Tomas, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charles, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Luis, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, Butzkueven, Helmut, and MSBase Study Group
Abstract: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, = 0.0016), worsening of disability (0.56, 0.38-0.82, = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, = 10) and worsening of disability (0.81, 0.67-0.99, = 0.043). Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
Published: 2021

18. Circulating microparticles reflect treatment effects and clinical status in multiple sclerosis

Author: Sáenz-Cuesta, Matías, Irizar, Haritz, Castillo-Triviño, Tamara, Muñoz-Culla, Maider, Osorio-Querejeta, Iñaki, Prada, Alvaro, Sepúlveda, Lucía, López-Mato, María P, de Munain, Adolfo López, Comabella, Manuel, Villar, Luisa M, Olascoaga, Javier, and Otaegui, David
Published: 2014
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19. Delay from treatment start to full effect of immunotherapies for multiple sclerosis (2679)

Author: Roos, Izanne, primary, Leray, Emmanuelle, additional, Frascoli, Federico, additional, Casey, Romain, additional, Brown, J William, additional, Horakova, Dana, additional, Havrdova, Eva, additional, Trojano, Maria, additional, Patti, Francesco, additional, Izquierdo, Guillermo, additional, Madueño, Sara Eichau, additional, Onofrj, Marco, additional, Lugaresi, Alessandra, additional, Prat, Alexandre, additional, Girard, Marc, additional, Grammond, Pierre, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Ozakbas, Serkan, additional, Bergamaschi, Roberto, additional, Sa, Maria Jose, additional, Cartechini, Elisabetta, additional, Boz, Cavit, additional, Granella, Franco, additional, Gerlach, Oliver, additional, Terzi, Murat, additional, Lechner-Scott, Jeannette, additional, Spitaleri, Daniele Litterio A., additional, Van Pesch, Vincent, additional, Soysal, Aysun, additional, Olascoaga, Javier, additional, Prevost, Julie, additional, Morales, Eduardo Aguera, additional, Slee, Mark, additional, Csepany, Tunde, additional, Turkoglu, Recai, additional, Sidhom, Youssef, additional, Gouider, Riadh, additional, Van Wijmeersch, Bart, additional, McCombe, Pamela, additional, Macdonell, Richard, additional, Coles, Alasdair, additional, Malpas, Charles, additional, Butzkueven, Helmut, additional, Vukusic, Sandra, additional, and Kalincik, Tomas, additional
Published: 2021
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20. Early clinical markers of aggressive multiple sclerosis.

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Malpas, Charles B, Manouchehrinia, Ali, Sharmin, Sifat, Roos, Izanne, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Eichau, Sara, Bergamaschi, Roberto, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Grand'Maison, Francois, Ozakbas, Serkan, Van Pesch, Vincent, Granella, Franco, Hupperts, Raymond, Pucci, Eugenio, Boz, Cavit, Sidhom, Youssef, Gouider, Riadh, Spitaleri, Daniele, Soysal, Aysun, Petersen, Thor, Verheul, Freek, Karabudak, Rana, Turkoglu, Recai, Ramo-Tello, Cristina, Terzi, Murat, Cristiano, Edgardo, Slee, Mark, McCombe, Pamela, Macdonell, Richard, Fragoso, Yara, Olascoaga, Javier, Altintas, Ayse, Olsson, Tomas, Butzkueven, Helmut, Hillert, Jan, Kalincik, Tomas, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Malpas, Charles B, Manouchehrinia, Ali, Sharmin, Sifat, Roos, Izanne, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Eichau, Sara, Bergamaschi, Roberto, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Grand'Maison, Francois, Ozakbas, Serkan, Van Pesch, Vincent, Granella, Franco, Hupperts, Raymond, Pucci, Eugenio, Boz, Cavit, Sidhom, Youssef, Gouider, Riadh, Spitaleri, Daniele, Soysal, Aysun, Petersen, Thor, Verheul, Freek, Karabudak, Rana, Turkoglu, Recai, Ramo-Tello, Cristina, Terzi, Murat, Cristiano, Edgardo, Slee, Mark, McCombe, Pamela, Macdonell, Richard, Fragoso, Yara, Olascoaga, Javier, Altintas, Ayse, Olsson, Tomas, Butzkueven, Helmut, Hillert, Jan, and Kalincik, Tomas
Abstract: Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence
Published: 2020

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

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Roos, Izanne, Leray, Emmanuelle, Frascoli, Federico, Casey, Romain, Brown, J William L, Horakova, Dana, Havrdova, Eva K, 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 B, Butzkueven, Helmut, Vukusic, Sandra, Kalincik, Tomas, MSBase, OFSEP investigators, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Roos, Izanne, Leray, Emmanuelle, Frascoli, Federico, Casey, Romain, Brown, J William L, Horakova, Dana, Havrdova, Eva K, 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 B, Butzkueven, Helmut, Vukusic, Sandra, Kalincik, Tomas, MSBase, and OFSEP investigators
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 1
Published: 2020

22. Risk of secondary progressive multiple sclerosis: A longitudinal study.

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Fambiatos, Adam, Jokubaitis, Vilija, Horakova, Dana, Kubala Havrdova, Eva, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Lugaresi, Alessandra, Izquierdo, Guillermo, Grand'Maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Alroughani, Raed, Terzi, Murat, Hupperts, Raymond, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Bergamaschi, Roberto, Van Pesch, Vincent, Ozakbas, Serkan, Granella, Franco, Turkoglu, Recai, Iuliano, Gerardo, Spitaleri, Daniele, McCombe, Pamela, Solaro, Claudio, Slee, Mark, Ampapa, Radek, Soysal, Aysun, Petersen, Thor, Sanchez-Menoyo, Jose Luis, Verheul, Freek, Prevost, Julie, Sidhom, Youssef, Van Wijmeersch, Bart, Vucic, Steve, Cristiano, Edgardo, Saladino, Maria Laura, Deri, Norma, Barnett, Michael, Olascoaga, Javier, Moore, Fraser, Skibina, Olga, Gray, Orla, Fragoso, Yara, Yamout, Bassem, Shaw, Cameron, Singhal, Bhim, Shuey, Neil, Hodgkinson, Suzanne, Altintas, Ayse, Al-Harbi, Talal, Csepany, Tunde, Taylor, Bruce, Hughes, Jordana, Jun, Jae-Kwan, van der Walt, Anneke, Spelman, Tim, Butzkueven, Helmut, Kalincik, Tomas, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Fambiatos, Adam, Jokubaitis, Vilija, Horakova, Dana, Kubala Havrdova, Eva, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Lugaresi, Alessandra, Izquierdo, Guillermo, Grand'Maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Alroughani, Raed, Terzi, Murat, Hupperts, Raymond, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Bergamaschi, Roberto, Van Pesch, Vincent, Ozakbas, Serkan, Granella, Franco, Turkoglu, Recai, Iuliano, Gerardo, Spitaleri, Daniele, McCombe, Pamela, Solaro, Claudio, Slee, Mark, Ampapa, Radek, Soysal, Aysun, Petersen, Thor, Sanchez-Menoyo, Jose Luis, Verheul, Freek, Prevost, Julie, Sidhom, Youssef, Van Wijmeersch, Bart, Vucic, Steve, Cristiano, Edgardo, Saladino, Maria Laura, Deri, Norma, Barnett, Michael, Olascoaga, Javier, Moore, Fraser, Skibina, Olga, Gray, Orla, Fragoso, Yara, Yamout, Bassem, Shaw, Cameron, Singhal, Bhim, Shuey, Neil, Hodgkinson, Suzanne, Altintas, Ayse, Al-Harbi, Talal, Csepany, Tunde, Taylor, Bruce, Hughes, Jordana, Jun, Jae-Kwan, van der Walt, Anneke, Spelman, Tim, Butzkueven, Helmut, and Kalincik, Tomas
Abstract: BACKGROUND: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested. OBJECTIVE: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis. METHODS: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed. RESULTS: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion. CONCLUSION: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
Published: 2020

23. Genome-wide significant association of ANKRD55 rs6859219 and multiple sclerosis risk

Author: Lill, Christina M, Schjeide, Brit-Maren M, Graetz, Christiane, Liu, Tian, Damotte, Vincent, Akkad, Denis A, Blaschke, Paul, Gerdes, Lisa-Ann, Kroner, Antje, Luessi, Felix, Cournu-Rebeix, Isabelle, Hoffjan, Sabine, Winkelmann, Alexander, Touze, Emmanuel, Pico, Fernando, Corcia, Philippe, Otaegui, David, Antigüedad, Alfredo, Alcina, Antonio, Comabella, Manuel, Montalban, Xavier, Olascoaga, Javier, Matesanz, Fuencisla, Dörner, Thomas, Li, Shu-Chen, Steinhagen-Thiessen, Elisabeth, Lindenberger, Ulman, Chan, Andrew, Rieckmann, Peter, Hartung, Hans-Peter, Aktas, Orhan, Lohse, Peter, Buttmann, Mathias, Kümpfel, Tania, Kubisch, Christian, Zettl, Uwe K, Epplen, Joerg T, Fontaine, Bertrand, Zipp, Frauke, Vandenbroeck, Koen, and Bertram, Lars
Published: 2013
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24. Identification of a functional variant in the KIF5A-CYP27B1-METTL1-FAM119B locus associated with multiple sclerosis

Author: Alcina, Antonio, Fedetz, Maria, Fernández, Óscar, Saiz, Albert, Izquierdo, Guillermo, Lucas, Miguel, Leyva, Laura, García-León, Juan-Antonio, Abad-Grau, María del Mar, Alloza, Iraide, Antigüedad, Alfredo, Garcia-Barcina, María J, Vandenbroeck, Koen, Varadé, Jezabel, de la Hera, Belén, Arroyo, Rafael, Comabella, Manuel, Montalban, Xavier, Petit-Marty, Natalia, Navarro, Arcadi, Otaegui, David, Olascoaga, Javier, Blanco, Yolanda, Urcelay, Elena, and Matesanz, Fuencisla
Published: 2013
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25. Early clinical markers of aggressive multiple sclerosis

Author: Malpas, Charles B, primary, Manouchehrinia, Ali, primary, Sharmin, Sifat, primary, Roos, Izanne, primary, Horakova, Dana, primary, Havrdova, Eva Kubala, primary, Trojano, Maria, primary, Izquierdo, Guillermo, primary, Eichau, Sara, primary, Bergamaschi, Roberto, primary, Sola, Patrizia, primary, Ferraro, Diana, primary, Lugaresi, Alessandra, primary, Prat, Alexandre, primary, Girard, Marc, primary, Duquette, Pierre, primary, Grammond, Pierre, primary, Grand’Maison, Francois, primary, Ozakbas, Serkan, primary, Van Pesch, Vincent, primary, Granella, Franco, primary, Hupperts, Raymond, primary, Pucci, Eugenio, primary, Boz, Cavit, primary, Sidhom, Youssef, primary, Gouider, Riadh, primary, Spitaleri, Daniele, primary, Soysal, Aysun, primary, Petersen, Thor, primary, Verheul, Freek, primary, Karabudak, Rana, primary, Turkoglu, Recai, primary, Ramo-Tello, Cristina, primary, Terzi, Murat, primary, Cristiano, Edgardo, primary, Slee, Mark, primary, McCombe, Pamela, primary, Macdonell, Richard, primary, Fragoso, Yara, primary, Olascoaga, Javier, primary, Altintas, Ayse, primary, Olsson, Tomas, primary, Butzkueven, Helmut, primary, Hillert, Jan, primary, and Kalincik, Tomas, primary
Published: 2020
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26. Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Author: Kunchok, Amy, primary, Malpas, Charles, additional, Nytrova, Petra, additional, Havrdova, Eva Kubala, additional, Alroughani, Raed, additional, Terzi, Murat, additional, Yamout, Bassem, additional, Hor, Jyh Yung, additional, Karabudak, Rana, additional, Boz, Cavit, additional, Ozakbas, Serkan, additional, Olascoaga, Javier, additional, Simo, Magdolna, additional, Granella, Franco, additional, Patti, Francesco, additional, McCombe, Pamela, additional, Csepany, Tunde, additional, Singhal, Bhim, additional, Bergamaschi, Roberto, additional, Fragoso, Yara, additional, Al-Harbi, Talal, additional, Turkoglu, Recai, additional, Lechner-Scott, Jeannette, additional, Laureys, Guy, additional, Oreja-Guevara, Celia, additional, Pucci, Eugenio, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Altintas, Ayse, additional, Soysal, Aysun, additional, Vucic, Steve, additional, Grand'Maison, Francois, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Lugaresi, Alessandra, additional, Onofrj, Marco, additional, Trojano, Maria, additional, Marriott, Mark, additional, Butzkueven, Helmut, additional, Kister, Ilya, additional, and Kalincik, Tomas, additional
Published: 2020
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27. MSJ868990_online_supplement – Supplemental material for Risk of secondary progressive multiple sclerosis: A longitudinal study

Author: Fambiatos, Adam, Jokubaitis, Vilija, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Lugaresi, Alessandra, Izquierdo, Guillermo, Francois Grand’Maison, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Alroughani, Raed, Terzi, Murat, Hupperts, Raymond, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Bergamaschi, Roberto, Pesch, Vincent Van, Ozakbas, Serkan, Granella, Franco, Turkoglu, Recai, Iuliano, Gerardo, Spitaleri, Daniele, McCombe, Pamela, Solaro, Claudio, Slee, Mark, Ampapa, Radek, Soysal, Aysun, Petersen, Thor, Sanchez-Menoyo, Jose Luis, Verheul, Freek, Prevost, Julie, Sidhom, Youssef, Wijmeersch, Bart Van, Vucic, Steve, Cristiano, Edgardo, Saladino, Maria Laura, Deri, Norma, Barnett, Michael, Olascoaga, Javier, Moore, Fraser, Skibina, Olga, Gray, Orla, Fragoso, Yara, Yamout, Bassem, Shaw, Cameron, Bhim Singhal, Shuey, Neil, Hodgkinson, Suzanne, Ayse Altintas, Al-Harbi, Talal, Tunde Csepany, Taylor, Bruce, Hughes, Jordana, Jun, Jae-Kwan, Walt, Anneke Van Der, Spelman, Tim, Butzkueven, Helmut, and Kalincik, Tomas
Subjects: FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract: Supplemental material, MSJ868990_online_supplement for Risk of secondary progressive multiple sclerosis: A longitudinal study by Adam Fambiatos, Vilija Jokubaitis, Dana Horakova, Eva Kubala Havrdova, Maria Trojano, Alexandre Prat, Marc Girard, Pierre Duquette, Alessandra Lugaresi, Guillermo Izquierdo, Francois Grand’Maison, Pierre Grammond, Patrizia Sola, Diana Ferraro, Raed Alroughani, Murat Terzi, Raymond Hupperts, Cavit Boz, Jeannette Lechner-Scott, Eugenio Pucci, Roberto Bergamaschi, Vincent Van Pesch, Serkan Ozakbas, Franco Granella, Recai Turkoglu, Gerardo Iuliano, Daniele Spitaleri, Pamela McCombe, Claudio Solaro, Mark Slee, Radek Ampapa, Aysun Soysal, Thor Petersen, Jose Luis Sanchez-Menoyo, Freek Verheul, Julie Prevost, Youssef Sidhom, Bart Van Wijmeersch, Steve Vucic, Edgardo Cristiano, Maria Laura Saladino, Norma Deri, Michael Barnett, Javier Olascoaga, Fraser Moore, Olga Skibina, Orla Gray, Yara Fragoso, Bassem Yamout, Cameron Shaw, Bhim Singhal, Neil Shuey, Suzanne Hodgkinson, Ayse Altintas, Talal Al-Harbi, Tunde Csepany, Bruce Taylor, Jordana Hughes, Jae-Kwan Jun, Anneke van der Walt, Tim Spelman, Helmut Butzkueven and Tomas Kalincik in Multiple Sclerosis Journal
Published: 2019
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28. Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

Author: Wilkins, Alastair, Slee, Mark, TERZİ, MURAT, Grand'Maison, Francois, Ferraro, Diana, Sola, Patrizia, Van Pesch, Vincent, McCombe, Pamela, Hupperts, Raymond, Alroughani, Raed, Grammond, Pierre, Bergamaschi, Roberto, Lugaresi, Alessandra, Shaygannejad, Vahid, Pucci, Eugenio, Granella, Franco, Jokubaitis, Vilija, Pearson, Owen R., Ziemssen, Tjalf, Hutchinson, Michael, McGuigan, Christopher, Butzkueven, Helmut, Kalincik, Tomas, Onofrj, Marco, Trojano, Maria, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Havrdova, Eva, Horakova, Dana, Zwanikken, Cees, Soysal, Aysun, Yamout, Bassem, Piroska, Imre, McDonnell, Gavin, Moore, Fraser, Butler, Ernest, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Hodgkinson, Suzanne, Oreja-Guevara, Celia, BOZ, CAVİT, Prevost, Julie, Olascoaga, Javier, Van Wijmeersch, Bart, Barnett, Michael, Verheul, Freek, Rojas, Juan Ingacio, Spitaleri, Daniele, Rio, Maria Edite, Taylor, Bruce, Luis Sanchez-Menoyo, Jose, Ramo-Tello, Cristina, Solaro, Claudio, Csepany, Tunde, Iuliano, Gerardo, Skibina, Olga, Petersen, Thor, Bolanos, Ricardo Fernandez, Sidhom, Youssef, Riadh, Riadh, Vucic, Steve, Macdonell, Richard, Sempere, Angel Perez, Simo, Magdolna, Kister, Ilya, Shuey, Neil, Radek, Radek, Dominguez, Jose Andres, Pia Amato, Maria, Saladino, Maria Laura, Kermode, Allan, Brown, J. William L., Coles, Alasdair, Lechner-Scott, Jeannette, Willis, Mark, Rice, Claire, Scolding, Neil, Flechter, Schlomo, Harding, Katharine, Jones, Joanne, Robertson, Neil, Hughes, Stella, ÖZAKBAŞ, SERKAN, Brown, J William L, Coles, Alasdair, Horakova, Dana, Havrdova, Eva, Izquierdo, Guillermo, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Trojano, Maria, Lugaresi, Alessandra, Bergamaschi, Roberto, Grammond, Pierre, Alroughani, Raed, Hupperts, Raymond, McCombe, Pamela, Van Pesch, Vincent, Sola, Patrizia, Ferraro, Diana, Grand'Maison, Francoi, Terzi, Murat, Lechner-Scott, Jeannette, Flechter, Schlomo, Slee, Mark, Shaygannejad, Vahid, Pucci, Eugenio, Granella, Franco, Jokubaitis, Vilija, Willis, Mark, Rice, Claire, Scolding, Neil, Wilkins, Alastair, Pearson, Owen R, Ziemssen, Tjalf, Hutchinson, Michael, Harding, Katharine, Jones, Joanne, McGuigan, Christopher, Butzkueven, Helmut, Kalincik, Toma, Robertson, Neil, Brown, Will [0000-0002-7737-5834], Coles, Alasdair [0000-0003-4738-0760], Jones, Joanna [0000-0003-4974-1371], Apollo - University of Cambridge Repository, DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and OMÜ
Subjects: Male, INTERFERON-BETA, MULTICENTER, Interferon-beta/therapeutic use, multiple sclerosis, 01 natural sciences, Cohort Studies, 0302 clinical medicine, Natalizumab, 030212 general & internal medicine, Alemtuzumab, Original Investigation, GLATIRAMER ACETATE, NATALIZUMAB, Natalizumab/therapeutic use, OUTCOMES, treatment, ALEMTUZUMAB, Absolute risk reduction, General Medicine, Immunologic Factors/therapeutic use, Fingolimod, TIME, Disease Progression, Female, Immunosuppressive Agents, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Alemtuzumab/therapeutic use, Lower risk, Time-to-Treatment, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Immunologic Factors, 0101 mathematics, Glatiramer acetate, Fingolimod Hydrochloride/therapeutic use, business.industry, Fingolimod Hydrochloride, Multiple sclerosis, DISABILITY, 010102 general mathematics, Glatiramer Acetate, Interferon-beta, Multiple Sclerosis, Relapsing-Remitting/drug therapy, medicine.disease, FINGOLIMOD, Immunosuppressive Agents/therapeutic use, multiple sclerosis, progression, treatment, progression, business, Glatiramer Acetate/therapeutic use
Abstract: none 40 si his study was financially supported by National Health and Medical Research Council of Australia (fellowships 1140766 and 1080518, project grants 1129189 and 1083539), the University of Melbourne (Faculty of Medicine, Dentistry and Health Sciences research fellowship), a Next Generation Fellowship funded by the Grand Charity of the Freemason’s (recipient JWLB), and the MSBase 2017 Fellowship (recipient JWLB). Alemtuzumab studies done in Cambridge were supported by the NIHR Cambridge Biomedical Research Centre and the MS Society UK. The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer Schering, Sanofi Genzyme, and Teva. IMPORTANCE: Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. OBJECTIVE: To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. DESIGN, SETTING, AND PARTICIPANTS: Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. EXPOSURES: The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). MAIN OUTCOME AND MEASURE: Conversion to objectively defined secondary progressive MS. RESULTS: Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P
Published: 2019

29. MSJ881994_supplementary_material – Supplemental material for Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype

Author: Zhou, Yuan, Claflin, Suzi B, Stankovich, Jim, Mei, Ingrid Van Der, Simpson, Steve, Roxburgh, Richard H, Kalincik, Tomas, Blizzard, Leigh, Lugaresi, Alessandra, Alroughani, Raed, Sajedi, Seyed Aidin, Butzkueven, Helmut, Pucci, Eugenio, Spitaleri, Daniele LA, Granella, Franco, Cristiano, Edgardo, Yamout, Bassem, Hughes, Stella, Gouider, Riadh, Menoyo, José Luis Sánchez, Olascoaga, Javier, McGuigan, Chris, Shaw, Cameron, Kermode, Allan G, Krisztian Kasa, Al-Harbi, Talal, Ayse Altintas, Laureys, Guy, Fragoso, Yara, Hardy, Todd A, Tunde Csepany, Carmen-Adella Sirbu, Decoo, Danny, Sas, Attila, Alvarez-Cermeño, Jose C, Kotkata, Karim, Millán-Pascual, Jorge, and Taylor, Bruce V
Subjects: FOS: Clinical medicine, 111702 Aged Health Care, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases
Abstract: Supplemental material, MSJ881994_supplementary_material for Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype by Yuan Zhou, Suzi B Claflin, Jim Stankovich, Ingrid van der Mei, Steve Simpson, Richard H Roxburgh, Tomas Kalincik, Leigh Blizzard, Alessandra Lugaresi, Raed Alroughani, Seyed Aidin Sajedi, Helmut Butzkueven, Eugenio Pucci, Daniele LA Spitaleri, Franco Granella, Edgardo Cristiano, Bassem Yamout, Stella Hughes, Riadh Gouider, José Luis Sánchez Menoyo, Javier Olascoaga, Chris McGuigan, Cameron Shaw, Allan G Kermode, Krisztian Kasa, Talal Al-Harbi, Ayse Altintas, Guy Laureys, Yara Fragoso, Todd A Hardy, Tunde Csepany, Carmen-Adella Sirbu, Danny Decoo, Attila Sas, Jose C Alvarez-Cermeño, Karim Kotkata, Jorge Millán-Pascual and Bruce V Taylor in Multiple Sclerosis Journal
Published: 2019
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30. Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Nguyen, Ai-Lan, Havrdova, Eva Kubala, Horakova, Dana, Izquierdo, Guillermo, Kalincik, Tomas, van der Walt, Anneke, Terzi, Murat, Alroughani, Raed, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Boz, Cavit, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Lechner-Scott, Jeannette, Barnett, Michael, Grand'Maison, Francois, Grammond, Pierre, Ramo-Tello, Cristina, Turkoglu, Recai, McCombe, Pamela, Pucci, Eugenio, Trojano, Maria, Granella, Franco, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Oreja-Guevara, Celia, Verheul, Freek, Vucic, Steve, Hodgkinson, Suzanne, Slee, Mark, Ampapa, Radek, Prevost, Julie, Menoyo, Jose Luis Sanchez, Skibina, Olga, Solaro, Claudio, Olascoaga, Javier, Shaw, Cameron, Madsen, Klaus Gregaard, Naidoo, Kerisha, Hyde, Robert, Butzkueven, Helmut, Jokubaitis, Vilija, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Nguyen, Ai-Lan, Havrdova, Eva Kubala, Horakova, Dana, Izquierdo, Guillermo, Kalincik, Tomas, van der Walt, Anneke, Terzi, Murat, Alroughani, Raed, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Boz, Cavit, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Lechner-Scott, Jeannette, Barnett, Michael, Grand'Maison, Francois, Grammond, Pierre, Ramo-Tello, Cristina, Turkoglu, Recai, McCombe, Pamela, Pucci, Eugenio, Trojano, Maria, Granella, Franco, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Oreja-Guevara, Celia, Verheul, Freek, Vucic, Steve, Hodgkinson, Suzanne, Slee, Mark, Ampapa, Radek, Prevost, Julie, Menoyo, Jose Luis Sanchez, Skibina, Olga, Solaro, Claudio, Olascoaga, Javier, Shaw, Cameron, Madsen, Klaus Gregaard, Naidoo, Kerisha, Hyde, Robert, Butzkueven, Helmut, and Jokubaitis, Vilija
Abstract: BACKGROUND: Exposure to disease-modifying therapy (DMT) during early pregnancy in women with relapsing-remitting MS (RRMS) may be increasing. OBJECTIVE: To retrospectively determine incidence of pregnancy, DMT exposure and pregnancy outcomes in women with RRMS. METHODS: We identified all women with RRMS aged 15-45 years in the MSBase Registry between 2005-2016. Annualised pregnancy incidence rates were calculated using Poisson regression models. DMT exposures and pregnancy outcomes were assessed. RESULTS: Of 9,098 women meeting inclusion criteria, 1,178 (13%) women recorded 1,521 pregnancies. The annualised incidence rate of pregnancy was 0.042 (95% CI 0.040, 0.045). A total of 635 (42%) reported pregnancies were conceived on DMT, increasing from 27% in 2006 to 62% in 2016. The median duration of DMT exposure during pregnancy was 30 days (IQR: 9, 50). There were a higher number of induced abortions on FDA pregnancy class C/D drugs compared with pregnancy class B and no DMT (p = 0.010); but no differences in spontaneous abortions, term or preterm births. CONCLUSIONS: We report low pregnancy incidence rates, with increasing number of pregnancies conceived on DMT over the past 12-years. The median duration of DMT exposure in pregnancy was relatively short at one month.
Published: 2019

31. El impacto de la depresion, ansiedad, estres y genero en el desarrollo de la disfuncion sexual en individuos afectos de Esclerosis Multiple

Author: Landa Maya, José Julián, Olascoaga, Javier, F. MEDICINA Y ODONTOLOGIA, MEDIKUNTZA ETA ODONTOLOGIA F., Grado en Medicina, Aymat Aguirre, Adriana, Landa Maya, José Julián, Olascoaga, Javier, F. MEDICINA Y ODONTOLOGIA, MEDIKUNTZA ETA ODONTOLOGIA F., Grado en Medicina, and Aymat Aguirre, Adriana
Abstract: [ES] Objetivo: El objetivo principal del proyecto es medir el impacto del estrés, depresión, ansiedad y género en el desarrollo de disfunción sexual en los individuos afectos de Esclerosis Múltiple del Hospital Universitario de Donostia. MÉTODOS: Se parte de dos cohortes según estados de discapacidad bajas o altas, con un total de 21 individuos en cada grupo (n=42). A los pacientes se les envía unos cuestionarios relacionados que miden la influencia que tienen nuestras variables en ellos, para posteriormente analizar los resultados. RESULTADOS: -Los pacientes que mostraron un estrés mantenido a menudo sintieron depresión en algún momento. -La mujer obtuvo significativamente niveles más altos de estrés que el varón.-Los pacientes que padecieron depresión además obtuvieron puntuaciones más bajas en el cuestionario que se relaciona con la calidad de vida. CONCLUSIONES: 1. Los pacientes que mostraban depresión fueron propensos a tener más problemas en su intimidad y relaciones sexuales, así como mayores niveles de ansiedad y estrés. 2. En nuestra muestra se ha comprobado una correlación entre los niveles de depresión con la calidad de vida, pero no con la disfunción sexual. 3. En cuanto al género, las mujeres han mostrado significativamente mayores niveles de estrés que el hombre.
Published: 2019

32. Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype

Author: Zhou, Yuan, primary, Claflin, Suzi B, additional, Stankovich, Jim, additional, van der Mei, Ingrid, additional, Simpson, Steve, additional, Roxburgh, Richard H, additional, Kalincik, Tomas, additional, Blizzard, Leigh, additional, Lugaresi, Alessandra, additional, Alroughani, Raed, additional, Sajedi, Seyed Aidin, additional, Butzkueven, Helmut, additional, Pucci, Eugenio, additional, Spitaleri, Daniele LA, additional, Granella, Franco, additional, Cristiano, Edgardo, additional, Yamout, Bassem, additional, Hughes, Stella, additional, Gouider, Riadh, additional, Sánchez Menoyo, José Luis, additional, Olascoaga, Javier, additional, McGuigan, Chris, additional, Shaw, Cameron, additional, Kermode, Allan G, additional, Kasa, Krisztian, additional, Al-Harbi, Talal, additional, Altintas, Ayse, additional, Laureys, Guy, additional, Fragoso, Yara, additional, Hardy, Todd A, additional, Csepany, Tunde, additional, Sirbu, Carmen-Adella, additional, Decoo, Danny, additional, Sas, Attila, additional, Alvarez-Cermeño, Jose C, additional, Kotkata, Karim, additional, Millán-Pascual, Jorge, additional, and Taylor, Bruce V, additional
Published: 2019
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33. ABO blood group distributions in multiple sclerosis patients from Basque Country; O- as a protective factor

Author: Lopetegi, Itziar, primary, Muñoz-Lopetegi, Amaia, additional, Arruti, Maialen, additional, Prada, Alvaro, additional, Urcelay, Sabin, additional, Olascoaga, Javier, additional, Otaegui, David, additional, and Castillo-Triviño, Tamara, additional
Published: 2019
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34. Risk of secondary progressive multiple sclerosis: A longitudinal study

Author: Fambiatos, Adam, primary, Jokubaitis, Vilija, additional, Horakova, Dana, additional, Kubala Havrdova, Eva, additional, Trojano, Maria, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Lugaresi, Alessandra, additional, Izquierdo, Guillermo, additional, Grand’Maison, Francois, additional, Grammond, Pierre, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Alroughani, Raed, additional, Terzi, Murat, additional, Hupperts, Raymond, additional, Boz, Cavit, additional, Lechner-Scott, Jeannette, additional, Pucci, Eugenio, additional, Bergamaschi, Roberto, additional, Van Pesch, Vincent, additional, Ozakbas, Serkan, additional, Granella, Franco, additional, Turkoglu, Recai, additional, Iuliano, Gerardo, additional, Spitaleri, Daniele, additional, McCombe, Pamela, additional, Solaro, Claudio, additional, Slee, Mark, additional, Ampapa, Radek, additional, Soysal, Aysun, additional, Petersen, Thor, additional, Sanchez-Menoyo, Jose Luis, additional, Verheul, Freek, additional, Prevost, Julie, additional, Sidhom, Youssef, additional, Van Wijmeersch, Bart, additional, Vucic, Steve, additional, Cristiano, Edgardo, additional, Saladino, Maria Laura, additional, Deri, Norma, additional, Barnett, Michael, additional, Olascoaga, Javier, additional, Moore, Fraser, additional, Skibina, Olga, additional, Gray, Orla, additional, Fragoso, Yara, additional, Yamout, Bassem, additional, Shaw, Cameron, additional, Singhal, Bhim, additional, Shuey, Neil, additional, Hodgkinson, Suzanne, additional, Altintas, Ayse, additional, Al-Harbi, Talal, additional, Csepany, Tunde, additional, Taylor, Bruce, additional, Hughes, Jordana, additional, Jun, Jae-Kwan, additional, van der Walt, Anneke, additional, Spelman, Tim, additional, Butzkueven, Helmut, additional, and Kalincik, Tomas, additional
Published: 2019
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35. Early clinical markers of aggressive multiple sclerosis

Author: Malpas, Charles B, primary, Manouchehrinia, Ali, additional, Sharmin, Sifat, additional, Roos, Izanne, additional, Horakova, Dana, additional, Havrdova, Eva Kubala, additional, Trojano, Maria, additional, Izquierdo, Guillermo, additional, Eichau, Sara, additional, Bergamaschi, Roberto, additional, Sola, Patrizia, additional, Ferraro, Diana, additional, Lugaresi, Alessandra, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Grammond, Pierre, additional, Grand’Maison, Francois, additional, Ozakbas, Serkan, additional, Van Pesch, Vincent, additional, Granella, Franco, additional, Hupperts, Raymond, additional, Pucci, Eugenio, additional, Boz, Cavit, additional, Iuliano, Gerardo, additional, Sidhom, Youssef, additional, Gouider, Riadh, additional, Spitaleri, Daniele, additional, Butzkueven, Helmut, additional, Soysal, Aysun, additional, Petersen, Thor, additional, Verheul, Freek, additional, Karabudak, Rana, additional, Turkoglu, Recai, additional, Ramo-Tello, Cristina, additional, Terzi, Murat, additional, Cristiano, Edgardo, additional, Slee, Mark, additional, McCombe, Pamela, additional, Macdonell, Richard, additional, Fragoso, Yara, additional, Olascoaga, Javier, additional, Altintas, Ayse, additional, Olsson, Tomas, additional, Hillert, Jan, additional, and Kalincik, Tomas, additional
Published: 2019
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36. Association of inflammation and disability accrual in patients with progressive-onset multiple sclerosis

Author: Hughes, Jordana, Jokubaitis, Vilija, Lugaresi, Alessandra, Hupperts, Raymond, Izquierdo, Guillermo, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grand'maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ramo-Tello, Cristina, Trojano, Maria, Slee, Mark, Shaygannejad, Vahid, Boz, Cavit, Lechner-Scott, Jeanette, Van Pesch, Vincent, Pucci, Eugenio, Solaro, Claudio, Verheul, Freek, Terzi, Murat, Granella, Franco, Spitaleri, Daniele, Alroughani, Raed, Jun, Jae-Kwan, Fambiatos, Adam, Van Der Walt, Anneke, Butzkueven, Helmut, Kalincik, Tomas, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, Di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Vitetta, Francesca, Simone, Anna Maria, Haartsen, Jodi, Spelman, Tim, Marriott, Mark, Kilpatrick, Trevor, King, John, Buzzard, Katherine, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Brown, J William L, Kunchok, Amy, Diamanti, Matteo, Cartechini, Elisabetta, Curti, Erica, Tsantes, Elena, Zwanikken, Cees, Rio, Maria Edite, Hughes, Stella, Amato, Maria Pita, Van Wijmeersch, Bart, Sanchez-Menoyo, Jose Luis, Bolaños, Ricardo Fernandez, Sajedi, Seyed Aidin, Iuliano, Gerardo, Den Braber-Moerland, Leontien, Prevost, Julie, Sempere, Angel Perez, Sidhom, Youssef, Butler, Ernest, Vucic, Steve, Taylor, Bruce, Cabrera-Gomez, Jose Antonio, Oreja-Guevara, Celia, Bergamaschi, Roberto, Turkoglu, Recai, Olascoaga, Javier, Cristiano, Edgardo, Rojas, Juan Ingacio, Hodgkinson, Suzanne, Skibina, Olga, Al-Harbi, Talal, Altintas, Ayse, McCombe, Pamela, Sinnige, LGF, Ozakbas, Serken, Saladino, Maria Laura, Bacile, Elizabeth Alejandra, Vrech, Carlos, Shaw, Cameron, Hughes, Jordana, Jokubaitis, Vilija, Lugaresi, Alessandra, Hupperts, Raymond, Izquierdo, Guillermo, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grand'maison, Francois, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ramo-Tello, Cristina, Trojano, Maria, Slee, Mark, Shaygannejad, Vahid, Boz, Cavit, Lechner-Scott, Jeanette, Van Pesch, Vincent, Pucci, Eugenio, Solaro, Claudio, Verheul, Freek, Terzi, Murat, Granella, Franco, Spitaleri, Daniele, Alroughani, Raed, Jun, Jae-Kwan, Fambiatos, Adam, Van Der Walt, Anneke, Butzkueven, Helmut, Kalincik, Tomas, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, Di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Vitetta, Francesca, Simone, Anna Maria, Haartsen, Jodi, Spelman, Tim, Marriott, Mark, Kilpatrick, Trevor, King, John, Buzzard, Katherine, Nguyen, Ai-Lan, Dwyer, Chris, Monif, Mastura, Brown, J William L, Kunchok, Amy, Diamanti, Matteo, Cartechini, Elisabetta, Curti, Erica, Tsantes, Elena, Zwanikken, Cees, Rio, Maria Edite, Hughes, Stella, Amato, Maria Pita, Van Wijmeersch, Bart, Sanchez-Menoyo, Jose Luis, Bolaños, Ricardo Fernandez, Sajedi, Seyed Aidin, Iuliano, Gerardo, Den Braber-Moerland, Leontien, Prevost, Julie, Sempere, Angel Perez, Sidhom, Youssef, Butler, Ernest, Vucic, Steve, Taylor, Bruce, Cabrera-Gomez, Jose Antonio, Oreja-Guevara, Celia, Bergamaschi, Roberto, Turkoglu, Recai, Olascoaga, Javier, Cristiano, Edgardo, Rojas, Juan Ingacio, Hodgkinson, Suzanne, Skibina, Olga, Al-Harbi, Talal, Altintas, Ayse, McCombe, Pamela, Sinnige, LGF, Ozakbas, Serken, Saladino, Maria Laura, Bacile, Elizabeth Alejandra, Vrech, Carlos, and Shaw, Cameron
Published: 2018

37. The First Dose of Fingolimod Affects Circulating Extracellular Vesicles in Multiple Sclerosis Patients

Author: Sáenz-Cuesta, Matías, primary, Alberro, Ainhoa, additional, Muñoz-Culla, Maider, additional, Osorio-Querejeta, Iñaki, additional, Fernandez-Mercado, Marta, additional, Lopetegui, Itziar, additional, Tainta, Mikel, additional, Prada, Álvaro, additional, Castillo-Triviño, Tamara, additional, Falcón-Pérez, Juan, additional, Olascoaga, Javier, additional, and Otaegui, David, additional
Published: 2018
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38. Reply to: Comment on Y.D. Fragoso et al.: “Lymphocyte count in peripheral blood is not associated with the level of clinical response to treatment with fingolimod” [Mult. Scler. Relat. Disord. (2017)]

Author: Fragoso, Yara Dadalti, primary, Spelman, Tim, additional, Boz, Cavit, additional, Alroughani, Raed, additional, Lugaresi, Alessandra, additional, Vucic, Steve, additional, Butzkueven, Helmut, additional, Terzi, Murat, additional, Havrdova, Eva, additional, Horakova, Dana, additional, Granella, Franco, additional, Olascoaga, Javier, additional, Menoyo, José Luis Sánchez, additional, Pucci, Eugenio, additional, Barnett, Michael, additional, Brooks, Joseph Bruno B., additional, and Haartsen, Jodi, additional
Published: 2018
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39. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis.

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lizak, Nathaniel, Lugaresi, Alessandra, Alroughani, Raed, Lechner-Scott, Jeannette, Slee, Mark, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Grammond, Pierre, Hupperts, Raymond, Grand'Maison, Francois, Sola, Patrizia, Pucci, Eugenio, Bergamaschi, Roberto, Oreja-Guevara, Celia, Van Pesch, Vincent, Ramo, Cristina, Spitaleri, Daniele, Iuliano, Gerardo, Boz, Cavit, Granella, Franco, Olascoaga, Javier, Verheul, Freek, Rozsa, Csilla, Cristiano, Edgardo, Flechter, Shlomo, Hodgkinson, Suzanne, Amato, Maria Pia, Deri, Norma, Jokubaitis, Vilija, Spelman, Tim, Butzkueven, Helmut, Kalincik, Tomas, MSBase Study Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lizak, Nathaniel, Lugaresi, Alessandra, Alroughani, Raed, Lechner-Scott, Jeannette, Slee, Mark, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Grammond, Pierre, Hupperts, Raymond, Grand'Maison, Francois, Sola, Patrizia, Pucci, Eugenio, Bergamaschi, Roberto, Oreja-Guevara, Celia, Van Pesch, Vincent, Ramo, Cristina, Spitaleri, Daniele, Iuliano, Gerardo, Boz, Cavit, Granella, Franco, Olascoaga, Javier, Verheul, Freek, Rozsa, Csilla, Cristiano, Edgardo, Flechter, Shlomo, Hodgkinson, Suzanne, Amato, Maria Pia, Deri, Norma, Jokubaitis, Vilija, Spelman, Tim, Butzkueven, Helmut, Kalincik, Tomas, and MSBase Study Group
Abstract: OBJECTIVE: To evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy. METHODS: The epochs between Expanded Disability Status Scale (EDSS) steps 3-6, 4-6 and 6-6.5 were analysed. Patients with relapse-onset MS and having reached 6-month confirmed baseline EDSS step (3/4/6) were identified in MSBase, a global observational MS cohort study. We used multivariable survival models to examine the impact of disease-modifying therapy, clinical and demographic factors on progression to the outcome EDSS step (6/6.5). Sensitivity analyses with varying outcome definitions and inclusion criteria were conducted. RESULTS: For the EDSS 3-6, 4-6 and 6-6.5 epochs, 1560, 1504 and 1231 patients were identified, respectively. Disability trajectories showed large coefficients of variance prebaseline (0.92-1.11) and postbaseline (2.15-2.50), with no significant correlations. The probability of reaching the outcome step was not associated with prebaseline variables, but was increased by higher relapse rates during each epoch (HRs 1.58-3.07; p<0.001). A greater proportion of each epoch treated with higher efficacy therapies was associated with lower risk of reaching the outcome disability step (HRs 0.72-0.91 per 25%; p≤0.02). 3 sensitivity analyses confirmed these results. CONCLUSIONS: Disease progression during moderately advanced and advanced MS is highly variable and amnesic to prior disease activity. Lower relapse rates and greater time on higher efficacy immunomodulatory therapy after reaching EDSS steps 3, 4 and 6 are associated with a decreased risk of accumulating further disability. Highly effective immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced relapse-onset MS.
Published: 2017

40. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Kalincik, Tomas, Brown, J William L, Robertson, Neil, Willis, Mark, Scolding, Neil, Rice, Claire M, Wilkins, Alastair, Pearson, Owen, Ziemssen, Tjalf, Hutchinson, Michael, McGuigan, Christopher, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Alroughani, Raed, Pucci, Eugenio, Sola, Patrizia, Hupperts, Raymond, Lechner-Scott, Jeannette, Terzi, Murat, Van Pesch, Vincent, Rozsa, Csilla, Grand'Maison, François, Boz, Cavit, Granella, Franco, Slee, Mark, Spitaleri, Daniele, Olascoaga, Javier, Bergamaschi, Roberto, Verheul, Freek, Vucic, Steve, McCombe, Pamela, Hodgkinson, Suzanne, Sanchez-Menoyo, Jose Luis, Ampapa, Radek, Simo, Magdolna, Csepany, Tunde, Ramo, Cristina, Cristiano, Edgardo, Barnett, Michael, Butzkueven, Helmut, Coles, Alasdair, MSBase Study Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Kalincik, Tomas, Brown, J William L, Robertson, Neil, Willis, Mark, Scolding, Neil, Rice, Claire M, Wilkins, Alastair, Pearson, Owen, Ziemssen, Tjalf, Hutchinson, Michael, McGuigan, Christopher, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Alroughani, Raed, Pucci, Eugenio, Sola, Patrizia, Hupperts, Raymond, Lechner-Scott, Jeannette, Terzi, Murat, Van Pesch, Vincent, Rozsa, Csilla, Grand'Maison, François, Boz, Cavit, Granella, Franco, Slee, Mark, Spitaleri, Daniele, Olascoaga, Javier, Bergamaschi, Roberto, Verheul, Freek, Vucic, Steve, McCombe, Pamela, Hodgkinson, Suzanne, Sanchez-Menoyo, Jose Luis, Ampapa, Radek, Simo, Magdolna, Csepany, Tunde, Ramo, Cristina, Cristiano, Edgardo, Barnett, Michael, Butzkueven, Helmut, Coles, Alasdair, and MSBase Study Group
Abstract: BACKGROUND: Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. METHODS: In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. FINDINGS: Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], p<0·0001) and fingolimod (0·15 [0·10-0·20] vs 0·34 [0·26-0·41], p<0·0001), and was associated with a similar annualised relapse rate as natalizumab (0·20 [0·14-0·26] vs 0·19 [0·15-0·23], p=0·78). For the disability outcome
Published: 2017

41. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Kalincik, Tomas, Manouchehrinia, Ali, Sobisek, Lukas, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Grammond, Pierre, Sola, Patrizia, Hupperts, Raymond, Grand'Maison, Francois, Pucci, Eugenio, Boz, Cavit, Alroughani, Raed, Van Pesch, Vincent, Lechner-Scott, Jeannette, Terzi, Murat, Bergamaschi, Roberto, Iuliano, Gerardo, Granella, Franco, Spitaleri, Daniele, Shaygannejad, Vahid, Oreja-Guevara, Celia, Slee, Mark, Ampapa, Radek, Verheul, Freek, McCombe, Pamela, Olascoaga, Javier, Amato, Maria Pia, Vucic, Steve, Hodgkinson, Suzanne, Ramo-Tello, Cristina, Flechter, Shlomo, Cristiano, Edgardo, Rozsa, Csilla, Moore, Fraser, Luis Sanchez-Menoyo, Jose, Laura Saladino, Maria, Barnett, Michael, Hillert, Jan, Butzkueven, Helmut, MSBase Study Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Kalincik, Tomas, Manouchehrinia, Ali, Sobisek, Lukas, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Grammond, Pierre, Sola, Patrizia, Hupperts, Raymond, Grand'Maison, Francois, Pucci, Eugenio, Boz, Cavit, Alroughani, Raed, Van Pesch, Vincent, Lechner-Scott, Jeannette, Terzi, Murat, Bergamaschi, Roberto, Iuliano, Gerardo, Granella, Franco, Spitaleri, Daniele, Shaygannejad, Vahid, Oreja-Guevara, Celia, Slee, Mark, Ampapa, Radek, Verheul, Freek, McCombe, Pamela, Olascoaga, Javier, Amato, Maria Pia, Vucic, Steve, Hodgkinson, Suzanne, Ramo-Tello, Cristina, Flechter, Shlomo, Cristiano, Edgardo, Rozsa, Csilla, Moore, Fraser, Luis Sanchez-Menoyo, Jose, Laura Saladino, Maria, Barnett, Michael, Hillert, Jan, Butzkueven, Helmut, and MSBase Study Group
Abstract: Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability
Published: 2017

42. Predictors of long-term disability accrual in relapse-onset multiple sclerosis

Author: Jokubaitis, Vilija G, Spelman, Tim, Kalincik, Tomas, Lorscheider, Johannes, Havrdova, Eva, Horakova, Dana, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Grammond, Pierre, Van Pesch, Vincent, Pucci, Eugenio, Grand'Maison, François, Hupperts, Raymond, Granella, Franco, Sola, Patrizia, Bergamaschi, Roberto, Iuliano, Gerardo, Spitaleri, Daniele, Boz, Cavit, Hodgkinson, Suzanne, Olascoaga, Javier, Verheul, Freek, McCombe, Pamela, Petersen, Thor, Rozsa, Csilla, Lechner-Scott, Jeannette, Saladino, Maria Laura, Farina, Deborah, Iaffaldano, Pietro, Paolicelli, Damiano, Butzkueven, Helmut, Lugaresi, Alessandra, Trojano, Maria, and MSBase Study Group
Subjects: Adult, Male, Multiple Sclerosis, Glatiramer Acetate, Interferon-beta, Protective Factors, Prognosis, Disability Evaluation, Young Adult, Pregnancy, Recurrence, Risk Factors, Humans, Female, Registries, Follow-Up Studies
Abstract: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis. Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed. We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009). We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.
Published: 2016

43. Neuromyelitis optica spectrum disorders Comparison according to the phenotype and serostatus

Author: Sepulveda, Maria, Armangue, Thas, Sola-Valls, Nuria, Arrambide, Georgina, Meca-Lallana, Jose E., Oreja-Guevara, Celia, Mendibe, Mar, Alvarez de Arcaya, Amaya, Aladro, Yolanda, Casanova, Bonaventura, Olascoaga, Javier, Jimenez-Huete, Adolfo, Fernandez-Fournier, Mireya, Ramio-Torrenta, Lluis, Cobo-Calvo, Alvaro, Vinals, Montserrat, de Andres, Clara, Meca-Lallana, Virginia, Cervello, Angeles, Calles, Carmen, Baron Rubio, Manuel, Ramo-Tello, Cristina, Caminero, Ana, Munteis, Elvira, Antiguedad, Alfredo R., Blanco, Yolanda, Villoslada, Pablo, Montalban, Xavier, Graus, Francesc, Saiz, Albert, and Spanish NMO Study Grp
Subjects: 0301 basic medicine, medicine.medical_specialty, Nervi òptic -- Malalties, Transverse myelitis, Serology, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Ulls -- Malalties i defectes, medicine, Optic neuritis, Clinical significance, Neuromyelitis optica, biology, Malalties del sistema nerviós central, business.industry, Hazard ratio, medicine.disease, Optic nerve -- Diseases, Nervis perifèrics -- Malalties, Nerves, Peripheral -- Diseases, Confidence interval, Malalties del nervi òptic, 030104 developmental biology, Neurology, Immunology, Optic nerve diseases, biology.protein, Neurology (clinical), business, Central nervous system diseases, 030217 neurology & neurosurgery
Abstract: Objective: To (1) determine the value of the recently proposed criteria of neuromyelitis optica (NMO) spectrum disorder (NMOSD) that unify patients with NMO and those with limited forms (NMO/LF) with aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies; and (2) investigate the clinical significance of the serologic status in patients with NMO. Methods: This was a retrospective, multicenter study of 181 patients fulfilling the 2006 NMO criteria (n = 127) or NMO/LF criteria with AQP4-IgG (n = 54). AQP4-IgG and myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies were tested using cell-based assays. Results: Patients were mainly white (86%) and female (ratio 6.5:1) with median age at onset 39 years (range 10-77). Compared to patients with NMO and AQP4-IgG (n = 94), those with NMO/LF presentedmore often with longitudinally extensive transverse myelitis (LETM) (p, This study was supported in part by Red Espanola de Esclerosis Multiple (REEM) Instituto de Salud Carlos III, Spain (RD07/0060/01, P.V.; RD12/0032/0002, A.S.; Marato de TV3 [20141830], F.G.) and Instituto de Salud Carlos III, Spain (CM14/00081; T.A.).
Published: 2016

44. Bilateral Retrobulbar Optic Neuropathy Associated With Golimumab

Author: de Frutos-Lezaun, Marta, primary, Bidaguren, Aritz, additional, de la Riva, Patricia, additional, Meneses, Carlos F., additional, and Olascoaga, Javier, additional
Published: 2017
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45. Progressive changes in non-coding RNA profile in leucocytes with age

Author: Muñoz-Culla, Maider, primary, Irizar, Haritz, additional, Gorostidi, Ana, additional, Alberro, Ainhoa, additional, Osorio-Querejeta, Iñaki, additional, Ruiz-Martínez, Javier, additional, Olascoaga, Javier, additional, López de Munain, Adolfo, additional, and Otaegui, David, additional
Published: 2017
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46. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study

Author: Kalincik, Tomas, primary, Brown, J William L, additional, Robertson, Neil, additional, Willis, Mark, additional, Scolding, Neil, additional, Rice, Claire M, additional, Wilkins, Alastair, additional, Pearson, Owen, additional, Ziemssen, Tjalf, additional, Hutchinson, Michael, additional, McGuigan, Christopher, additional, Jokubaitis, Vilija, additional, Spelman, Tim, additional, Horakova, Dana, additional, Havrdova, Eva, additional, Trojano, Maria, additional, Izquierdo, Guillermo, additional, Lugaresi, Alessandra, additional, Prat, Alexandre, additional, Girard, Marc, additional, Duquette, Pierre, additional, Grammond, Pierre, additional, Alroughani, Raed, additional, Pucci, Eugenio, additional, Sola, Patrizia, additional, Hupperts, Raymond, additional, Lechner-Scott, Jeannette, additional, Terzi, Murat, additional, Van Pesch, Vincent, additional, Rozsa, Csilla, additional, Grand'Maison, François, additional, Boz, Cavit, additional, Granella, Franco, additional, Slee, Mark, additional, Spitaleri, Daniele, additional, Olascoaga, Javier, additional, Bergamaschi, Roberto, additional, Verheul, Freek, additional, Vucic, Steve, additional, McCombe, Pamela, additional, Hodgkinson, Suzanne, additional, Sanchez-Menoyo, Jose Luis, additional, Ampapa, Radek, additional, Simo, Magdolna, additional, Csepany, Tunde, additional, Ramo, Cristina, additional, Cristiano, Edgardo, additional, Barnett, Michael, additional, Butzkueven, Helmut, additional, and Coles, Alasdair, additional
Published: 2017
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47. Predictors of long-term disability accrual in relapse-onset multiple sclerosis

Author: Jokubaitis, Vilija G., Spelman, Tim, Kalincik, Tomas, Lorscheider, Johannes, Havrdova, Eva, Horakova, Dana, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Grammond, Pierre, Van Pesch, Vincent, Pucci, Eugenio, Grand'Maison, Francois, Hupperts, Raymond, Granella, Franco, Sola, Patrizia, Bergamaschi, Roberto, Iuliano, Gerardo, Spitaleri, Daniele, Boz, Cavit, Hodgkinson, Suzanne, Olascoaga, Javier, Verheul, Freek, McCombe, Pamela, Petersen, Thor, Rozsa, Csilla, Lechner-Scott, Jeannette, Laura Saladino, Maria, Farina, Deborah, Iaffaldano, Pietro, Paolicelli, Damiano, Butzkueven, Helmut, Lugaresi, Alessandra, Trojano, Maria, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), and Klinische Neurowetenschappen
Subjects: Adult, Male, Multiple Sclerosis, Glatiramer Acetate, Interferon-beta, Protective Factors, Prognosis, Disability Evaluation, Young Adult, Pregnancy, Recurrence, Risk Factors, Journal Article, Humans, Female, Registries, Follow-Up Studies
Abstract: OBJECTIVE: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis.METHODS: Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed.RESULTS: We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009).INTERPRETATION: We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.
Published: 2015

48. Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented at the 7th Post-ECTRIMS meeting (I)

Author: Fernandez, Oscar, Alvarez-Cermeno, Jose C., Arroyo, Rafael, Brieva, Lluis, Carmen Calles-Hernandez, M., Casanova-Estruch, Bonaventura, Comabella, Manuel, Garcia-Merino, Juan A., Ginestal, Ricardo, Izquierdo, Guillermo, Meca-Lallana, Jose E., del Mar Mendibe-Bilbao, Maria, Montalban, Xavier, Munoz-Garcia, Delicias, Olascoaga, Javier, Oliva-Nacarino, Pedro, Oreja-Guevara, Celia, Ramio-Torrenta, Lluis, Romero-Pinel, Lucia, Rodriguez-Antigueedad, Alfredo, Saiz, Albert, and Tintore, Mar
Published: 2015

49. ABO blood group distributions in multiple sclerosis patients from Basque Country; O- as a protective factor.

Author: Lopetegi, Itziar, Maialen Arruti, Amaia Munoz-Lopetegi, Prada, Alvaro, Urcelay, Sabin, Olascoaga, Javier, Otaegui, David, and Castillo-Trivino, Tamara
Abstract: Background: The relation between ABO/Rh groups and multiple sclerosis (MS) has been proposed in several studies, however there is a controversy about the role of these groups in the disease. Although it has been reported that some groups can be protective or risk factors, there is no consensus and discordant reports can be found in the literature. Objectives and methodology: In this short report, we analyze the ABO/Rh distribution in a MS cohort of 265 patients and compare these frequencies with the results obtained from the Basque Blood Donors bank (17,796 individuals) of the same region. Results and conclusions: From our data, the absence of immune antigens (A, B or Rhesus +) defined by the group O- seems to be protective in the MS group with an odds ratio of 0.49 (95% confidence interval 0.309-0.796), while the presence of Rh+ plus A or B seems to be a risk in developing multiple sclerosis. [ABSTRACT FROM AUTHOR]
Published: 2019
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50. Defining secondary progressive multiple sclerosis.

Author: UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lorscheider, Johannes, Buzzard, Katherine, Jokubaitis, Vilija, Spelman, Tim, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Girard, Marc, Duquette, Pierre, Prat, Alexandre, Lugaresi, Alessandra, Grand'Maison, François, Grammond, Pierre, Hupperts, Raymond, Alroughani, Raed, Sola, Patrizia, Boz, Cavit, Pucci, Eugenio, Lechner-Scott, Jeanette, Bergamaschi, Roberto, Oreja-Guevara, Celia, Iuliano, Gerardo, Van Pesch, Vincent, Granella, Franco, Ramo-Tello, Cristina, Spitaleri, Daniele, Petersen, Thor, Slee, Mark, Verheul, Freek, Ampapa, Radek, Amato, Maria Pia, McCombe, Pamela, Vucic, Steve, Sánchez Menoyo, José Luis, Cristiano, Edgardo, Barnett, Michael H, Hodgkinson, Suzanne, Olascoaga, Javier, Saladino, Maria Laura, Gray, Orla, Shaw, Cameron, Moore, Fraser, Butzkueven, Helmut, Kalincik, Tomas, MSBase Study Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Lorscheider, Johannes, Buzzard, Katherine, Jokubaitis, Vilija, Spelman, Tim, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Girard, Marc, Duquette, Pierre, Prat, Alexandre, Lugaresi, Alessandra, Grand'Maison, François, Grammond, Pierre, Hupperts, Raymond, Alroughani, Raed, Sola, Patrizia, Boz, Cavit, Pucci, Eugenio, Lechner-Scott, Jeanette, Bergamaschi, Roberto, Oreja-Guevara, Celia, Iuliano, Gerardo, Van Pesch, Vincent, Granella, Franco, Ramo-Tello, Cristina, Spitaleri, Daniele, Petersen, Thor, Slee, Mark, Verheul, Freek, Ampapa, Radek, Amato, Maria Pia, McCombe, Pamela, Vucic, Steve, Sánchez Menoyo, José Luis, Cristiano, Edgardo, Barnett, Michael H, Hodgkinson, Suzanne, Olascoaga, Javier, Saladino, Maria Laura, Gray, Orla, Shaw, Cameron, Moore, Fraser, Butzkueven, Helmut, Kalincik, Tomas, and MSBase Study Group
Abstract: A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple sclerosis b
Published: 2016

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