Vilija G Jokubaitis1,2, Tim Spelman1, Tomas Kalincik1,2, Johannes Lorscheider1,2, Eva Havrdova3, Dana Horakova3, Pierre Duquette4, Marc Girard4, Alexandre Prat4, Guillermo Izquierdo5, Pierre Grammond6, Vincent Van Pesch7, Eugenio Pucci8, François Grand'Maison9, Raymond Hupperts10, Franco Granella11, Patrizia Sola12, Roberto Bergamaschi13, Gerardo Iuliano14, Daniele Spitaleri15, Cavit Boz16, Suzanne Hodgkinson17, Javier Olascoaga18, Freek Verheul19, Pamela McCombe20, Thor Petersen21, Csilla Rozsa22, Jeannette Lechner-Scott23, Maria Laura Saladino24, Deborah Farina25, Pietro Iaffaldano26, Damiano Paolicelli26, Helmut Butzkueven1,2,27, Alessandra Lugaresi28,29, Maria Trojano26. 1. Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia. 2. Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia. 3. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, General University Hospital and Charles University in Prague, Prague, Czech Republic. 4. Centre Hospitalier de l'Université de Montréal, Notre Dame Hospital, Montreal, Quebec, Canada. 5. Hospital Universitario Virgen Macarena, Seville, Spain. 6. Centre de réadaptation déficience physique Chaudière-Appalache, Lévis, Quebec, Canada. 7. Cliniques Universitaires Saint-Luc, Brussels, Belgium. 8. Neurology Unit, Azienda Sanitaria Unica Regionale Marche AV3, Macerata, Italy. 9. Neuro Rive-Sud, Charles LeMoyne Hospital, Greenfield Park, Quebec, Canada. 10. Zuyderland Ziekenhuis, Sittard, The Netherlands. 11. University of Parma, Parma, Italy. 12. Nuovo Ospedale Civile S.Agostino/Estense, Modena, Italy. 13. C. Mondino National Neurological Institute, Pavia, Italy. 14. Ospedali Riuniti di Salerno, Salerno, Italy. 15. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati, Avellino, Italy. 16. Karadeniz Technical University, Trabzon, Turkey. 17. Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia. 18. Donostia Hospital, San Sebastián, Spain. 19. Groene Hart Ziekenhuis, Gouda, The Netherlands. 20. Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia. 21. Kommunehospitalet, Arhus C, Denmark. 22. Jahn Ferenc Teaching Hospital, Budapest, Hungary. 23. John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia. 24. Instituto de Neurociencias Buenos Aires, Buenos Aires, Argentina. 25. MS Center, Department of Neuroscience, Imaging and Clinical Sciences, G. d'Annunzio University, Chieti, Italy. 26. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 27. Department of Neurology, Box Hill Hospital, Monash University, Box Hill, Victoria, Australia. 28. Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum-University of Bologna, Bologna, Italy. 29. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
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.
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.
Authors: Maria Trojano; Mar Tintore; Xavier Montalban; Jan Hillert; Tomas Kalincik; Pietro Iaffaldano; Tim Spelman; Maria Pia Sormani; Helmut Butzkueven Journal: Nat Rev Neurol Date: 2017-01-13 Impact factor: 42.937
Authors: Claudio Gasperini; Luca Prosperini; Mar Tintoré; Maria Pia Sormani; Massimo Filippi; Jordi Rio; Jacqueline Palace; Maria A Rocca; Olga Ciccarelli; Frederik Barkhof; Jaume Sastre-Garriga; Hugo Vrenken; Jette L Frederiksen; Tarek A Yousry; Christian Enzinger; Alex Rovira; Ludwig Kappos; Carlo Pozzilli; Xavier Montalban; Nicola De Stefano Journal: Neurology Date: 2018-12-26 Impact factor: 9.910
Authors: Riley Bove; Tanuja Chitnis; Bruce Ac Cree; Mar Tintoré; Yvonne Naegelin; Bernard Mj Uitdehaag; Ludwig Kappos; Samia J Khoury; Xavier Montalban; Stephen L Hauser; Howard L Weiner Journal: Mult Scler Date: 2017-08-29 Impact factor: 6.312