Nathaniel Lizak1,2, Charles B Malpas1,3, Sifat Sharmin1,3, Eva Kubala Havrdova4, Dana Horakova4, Guillermo Izquierdo5, Sara Eichau5, Alessandra Lugaresi6,7, Pierre Duquette8,9, Marc Girard8,9, Alexandre Prat8,9, Catherine Larochelle8,9, Maria Trojano10, Francois Grand'Maison11, Pierre Grammond12, Patrizia Sola13, Diana Ferraro13, Raymond Hupperts14, Roberto Bergamaschi15, Cavit Boz16, Vincent Van Pesch17,18, Daniele Spitaleri19, Murat Terzi20, Tomas Kalincik1,3. 1. Clinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia. 2. Department of Medicine, The Alfred Hospital, Melbourne, Victoria, Australia. 3. Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia. 4. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. 5. Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena, Seville, Spain. 6. Istituto delle Scienze Neurologiche di Bologna, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Unita Operative Semplici d'Istituto (UOSI) Riabilitazione Sclerosi Multipla, Bologna, Italy. 7. Dipartimento di Scienze Biomediche e Neuromotorie, Universita di Bologna, Bologna, Italy. 8. Department of Neurology, Hopital Notre Dame, Montreal, Quebec, Canada. 9. Department of Medicine, Centre Hospitalier de l'Universite de Montreal, Universite de Montreal, Montreal, Quebec, Canada. 10. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 11. Neuro Rive-Sud, Quebec, Canada. 12. Integrated Health and Social Services Centres (CISSS), Chaudiere-Appalaches, Levis, Quebec, Canada. 13. Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy. 14. Department of Neurology, Zuyderland Ziekenhuis, Sittard, the Netherlands. 15. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Mondino Foundation, Pavia, Italy. 16. Medical Faculty, Farabi Hospital, Karadeniz Technical University, Trabzon, Turkey. 17. Department of Laboratory Medicine, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 18. Neurochemistry Unit, Institute of Neuroscience, Universite Catholique de Louvain, Louvain-la-Neuve, Belgium. 19. Institute of Neurology, Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy. 20. Medical Faculty, 19 Mayis University, Samsun, Turkey.
Abstract
Importance: It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). Objective: To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation. Design, Setting, and Participants: In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53 680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020. Exposures: The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated. Main Outcomes and Measures: Two outcomes were analyzed as measures of disability accumulation during SPMS: the rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models). Results: Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P = .009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent. Conclusions and Relevance: In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study's results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.
Importance: It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). Objective: To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation. Design, Setting, and Participants: In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53 680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020. Exposures: The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated. Main Outcomes and Measures: Two outcomes were analyzed as measures of disability accumulation during SPMS: the rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models). Results: Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P = .009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent. Conclusions and Relevance: In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study's results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.
Authors: Tomas Kalincik; Ibrahima Diouf; Sifat Sharmin; Charles Malpas; Tim Spelman; Dana Horakova; Eva Kubala Havrdova; Maria Trojano; Guillermo Izquierdo; Alessandra Lugaresi; Alexandre Prat; Marc Girard; Pierre Duquette; Pierre Grammond; Vilija Jokubaitis; Anneke van der Walt; Francois Grand'Maison; Patrizia Sola; Diana Ferraro; Vahid Shaygannejad; Raed Alroughani; Raymond Hupperts; Murat Terzi; Cavit Boz; Jeannette Lechner-Scott; Eugenio Pucci; Vincent Van Pesch; Franco Granella; Roberto Bergamaschi; Daniele Spitaleri; Mark Slee; Steve Vucic; Radek Ampapa; Pamela McCombe; Cristina Ramo-Tello; Julie Prevost; Javier Olascoaga; Edgardo Cristiano; Michael Barnett; Maria Laura Saladino; Jose Luis Sanchez-Menoyo; Suzanne Hodgkinson; Csilla Rozsa; Stella Hughes; Fraser Moore; Cameron Shaw; Ernest Butler; Olga Skibina; Orla Gray; Allan Kermode; Tunde Csepany; Bhim Singhal; Neil Shuey; Imre Piroska; Bruce Taylor; Magdolna Simo; Carmen-Adella Sirbu; Attila Sas; Helmut Butzkueven Journal: Neurology Date: 2020-12-28 Impact factor: 9.910
Authors: Alan J Thompson; William Carroll; Olga Ciccarelli; Giancarlo Comi; Anne Cross; Alexis Donnelly; Anthony Feinstein; Robert J Fox; Anne Helme; Reinhard Hohlfeld; Robert Hyde; Pamela Kanellis; Douglas Landsman; Catherine Lubetzki; Ruth Ann Marrie; Julia Morahan; Xavier Montalban; Bruno Musch; Sarah Rawlings; Marco Salvetti; Finn Sellebjerg; Caroline Sincock; Kathryn E Smith; Jon Strum; Paola Zaratin; Timothy Coetzee Journal: Mult Scler Date: 2021-12-01 Impact factor: 6.312