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.

Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino Italy

C Mondino National Neurological Institute Pavia Italy

Centre de réadaptation déficience physique Chaudière Appalache Lévis Quebec Canada

Centre for Clinical Research University of Queensland Brisbane Queensland Australia

Centre Hospitalier de l'Université de Montréal Notre Dame Hospital Montreal Quebec Canada

Cliniques Universitaires Saint Luc Brussels Belgium

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Biomedical and Neuromotor Sciences Alma Mater Studiorum University of Bologna Bologna Italy

Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital University of Melbourne Melbourne Victoria Australia

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine General University Hospital and Charles University Prague Prague Czech Republic

Department of Neurology Box Hill Hospital Monash University Box Hill Victoria Australia

Department of Neurology Liverpool Hospital Liverpool New South Wales Australia

Department of Neurology Royal Melbourne Hospital Melbourne Victoria Australia

Donostia Hospital San Sebastián Spain

Groene Hart Ziekenhuis Gouda The Netherlands

Hospital Universitario Virgen Macarena Seville Spain

Instituto de Neurociencias Buenos Aires Buenos Aires Argentina

IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy

Jahn Ferenc Teaching Hospital Budapest Hungary

John Hunter Hospital University of Newcastle Newcastle New South Wales Australia

Karadeniz Technical University Trabzon Turkey

Kommunehospitalet Arhus C Denmark

MS Center Department of Neuroscience Imaging and Clinical Sciences G d'Annunzio University Chieti Italy

Neuro Rive Sud Charles LeMoyne Hospital Greenfield Park Quebec Canada

Neurology Unit Azienda Sanitaria Unica Regionale Marche AV3 Macerata Italy

Nuovo Ospedale Civile S Agostino Estense Modena Italy

Ospedali Riuniti di Salerno Salerno Italy

University of Parma Parma Italy

Zuyderland Ziekenhuis Sittard The Netherlands

References provided by Crossref.org

Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis

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Using personalized prognosis in the treatment of relapsing multiple sclerosis: A practical guide

Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

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

Association of Sustained Immunotherapy With Disability Outcomes in Patients With Active Secondary Progressive Multiple Sclerosis

Management of multiple sclerosis patients in central European countries: current needs and potential solutions