title: Excess Mortality in Patients with Multiple Sclerosis Starts at 20 Years from Clinical Onset: Data from a Large-Scale French Observational Study.
abstract: BACKGROUND
  Recent studies in multiple sclerosis (MS) showed longer survival times from clinical onset than older hospital-based series. However estimated median time ranges widely, from 24 to 45 years, which makes huge difference for patients as this neurological disease mainly starts around age 20 to 40. Precise and up-to-date reference data about mortality in MS are crucial for patients and neurologists, but unavailable yet in France.
  
  
  OBJECTIVE
  Estimate survival in MS patients and compare mortality with that of the French general population.
  
  
  METHODS
  We conducted a multicenter observational study involving clinical longitudinal data from 30,413 eligible patients, linked to the national deaths register. Inclusion criteria were definite MS diagnosis and clinical onset prior to January, 1st 2009 in order to get a minimum of 1-year disease duration.
  
  
  RESULTS
  After removing between-center duplicates and applying inclusion criteria, the final population comprised 27,603 MS patients (F/M sex ratio 2.5, mean age at onset 33.0 years, 85.5% relapsing onset). During the follow-up period (mean 15.2 +/- 10.3 years), 1569 deaths (5.7%) were identified; half related to MS. Death rates were significantly higher in men, patients with later clinical onset, and in progressive MS. Overall excess mortality compared with the general population was moderate (Standardized Mortality Ratio 1.48, 95% confidence interval [1.41-1.55]), but increased considerably after 20 years of disease (2.20 [2.10-2.31]).
  
  
  CONCLUSIONS
  This study revealed a moderate decrease in life expectancy in MS patients, and showed that the risk of dying is strongly correlated to disease duration and disability, highlighting the need for early actions that can slow disability progression.
authors.affiliation: Department of Epidemiology, EHESP Rennes, Sorbonne Paris Cité; CIC-P 1414, CHU Rennes, West Neuroscience Network of Excellence (WENNE), Rennes, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leray
authors.affiliation: Department of Neurology, CHU Lyon, Observatoire Français de la Sclérose En Plaques (OFSEP), Lyon, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Vukusic
authors.affiliation: ReLSEP, Lorraine Register of MS, EA 4360, Department of Neurology, CHU Nancy, Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Debouverie
authors.affiliation: Department of Neurology, CHU Toulouse, Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Clanet
authors.affiliation: Department of Neurology, CHU Bordeaux, Bordeaux, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Brochet
authors.affiliation: Department of Neurology, Hopitaux Universitaire de Strasbourg, Clinical investigation center (CIC INSERM 1434) and UMR INSERM 1119/Federation de Medecine translationnelle (FMTS), Strasbourg, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: de Sèze
authors.affiliation: Université de Lille, Department of Neurology, Hôpital Roger Salengro, CHRU de Lille, Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Zéphir
authors.affiliation: Department of Neurology, CHU Caen, Caen, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Defer
authors.affiliation: Department of Neurology, CHU Nice, Nice, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lebrun-Frenay
authors.affiliation: Department of Neurology, CHU Dijon, Dijon, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Moreau
authors.affiliation: Department of Neurology, CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Clavelou
authors.affiliation: APHM, Hôpital de La Timone, Pôle de Neurosciences Cliniques, Department of Neurology, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Department of Neurology, CHU Besançon, Besançon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Berger
authors.affiliation: Department of Neurology, CHU de Martinique, Martinique, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Cabre
authors.affiliation: Department of Neurology, CHU Saint-Etienne, Saint-Etienne, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Camdessanché
authors.affiliation: Department of Epidemiology, EHESP Rennes, Sorbonne Paris Cité, Paris, France.
authors.forename: Shoshannah
authors.initials: S
authors.lastname: Kalson-Ray
authors.affiliation: Department of Neurology, CHU Lyon, Lyon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Confavreux
authors.affiliation: Department of Neurology, CHU Rennes, WEst Neuroscience Network of Excellence (WENNE), Rennes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Edan
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D008017:Life Expectancy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000401:mortality*; D012042:Registries; D012189:Retrospective Studies; D012737:Sex Factors