https://doi.org/10.1177/1352458519868990 https://doi.org/10.1177/1352458519868990 MULTIPLE SCLEROSIS MSJ JOURNAL journals.sagepub.com/home/msj 1 Multiple Sclerosis Journal 1–12 DOI: 10.1177/ 1352458519868990 © The Author(s), 2019. Article reuse guidelines: sagepub.com/journals- permissions Introduction Previous efforts to identify prognostic markers of sec- ondary progressive multiple sclerosis (SPMS) have used large natural history cohorts, limited to certain geographic location and composed of mostly untreated patients. As a result, they do not take into considera- tion the impact that disease-modifying therapy (DMT) has on delaying SPMS. 1 Furthermore, the compara- bility of these studies is hampered by the use of vary- ing methodologies and outcomes, including different Risk of secondary progressive multiple sclerosis: A longitudinal study 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 on behalf of the MSBase Study Group* 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 dis- ability scores were selected from MSBase, a global observational cohort. The risk of conversion to objec- tively 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 Sta- tus 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. Keywords: SPMS, multiple sclerosis, disease modifying therapies, prediction, prognostics Date received: 6 February 2019; revised: 6 May 2019; accepted: 12 June 2019. Correspondence to: T Kalincik L4 Centre, Melbourne Brain Centre at Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050, Australia. tomas.kalincik@unimelb. edu.au Adam Fambiatos Jordana Hughes Jae-Kwan Jun CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia Vilija Jokubaitis Anneke van der Walt Central Clinical School, Monash University, Melbourne, VIC, Australia The Alfred, Melbourne, VIC, Australia Dana Horakova Eva Kubala Havrdova Department of Neurology and Center of Clinical Neuroscience, General University Hospital and Charles University in Prague, Prague, Czech Republic Maria Trojano Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy Alexandre Prat Marc Girard Pierre Duquette Hopital Notre-Dame, Montreal, QC, Canada/ CHUM and Universite de Montreal, Montreal, QC, Canada 868990MSJ 0 0 10.1177/1352458519868990Multiple Sclerosis JournalA Fambiatos, V Jokubaitis research-article2019 2019 Original Research Paper