title: A 10-year follow-up of the European multicenter trial of interferon β-1b in secondary-progressive multiple sclerosis.
abstract: OBJECTIVE
  To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b).
  
  
  METHODS
  We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied.
  
  
  RESULTS
  Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R(2): 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R(2): 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability.
  
  
  CONCLUSIONS
  The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel/Blizard Institute, Queen Mary University of London, Barts, UK/London School of Medicine and Dentistry, UK University Hospital Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Kuhle
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel.
authors.forename: M
authors.initials: M
authors.lastname: Hardmeier
authors.affiliation: Blizard Institute, Queen Mary University of London, Barts, UK/London School of Medicine and Dentistry, UK. Neurocentre of Southern Switzerland, Ospedale Civico, Lugano, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Disanto
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel.
authors.forename: K
authors.initials: K
authors.lastname: Gugleta
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel.
authors.forename: M
authors.initials: M
authors.lastname: Ecsedi
authors.affiliation: Department of Medicine, Neurology, Kantonsspital Baselland Bruderholz, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Lienert
authors.affiliation: Department NEUROFARBA, Section Neurosciences, University of Florence, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Amato
authors.affiliation: Department of Neurology, Klinik Hennigsdorf, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Baum
authors.affiliation: Department of Neurology, University of Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Buttmann
authors.affiliation: Department of Neurology, Klinikum Augsburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bayas
authors.affiliation: Unité Institut national de la santé et de la recherche médicale (INSERM) 563, Centre hospitalier universitaire Purpan, Toulouse, France.
authors.forename: D
authors.initials: D
authors.lastname: Brassat
authors.affiliation: Department of Neurology, and INSERM-CHU CIC-P 0005, Centre hospitalier universitaire de Bordeaux, France.
authors.forename: B
authors.initials: B
authors.lastname: Brochet
authors.affiliation: Centre de coordination EDMUS pour la sclérose en plaques, Hôpital Neurologique Pierre-Wertheimer, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Confavreux
authors.affiliation: Department of Neurology, Centre hospitalier universitaire Pontchaillou, Rennes, France.
authors.forename: G
authors.initials: G
authors.lastname: Edan
authors.affiliation: Department of Neurology, Central Hospital, Helsinki University, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Färkkilä
authors.affiliation: Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Fredrikson
authors.affiliation: Department of Neurological Sciences, University of Rome La Sapienza, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Frontoni
authors.affiliation: Department of Neurology, National MS Center, Melsbroek, Belgium/Vrije Universiteit Brussel, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: D'Hooghe
authors.affiliation: Saint Vincent's University Hospital, University College Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Hutchinson
authors.affiliation: Departments of Neurology, University Medical Center Groningen, Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: De Keyser
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: B C
authors.initials: BC
authors.lastname: Kieseier
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kümpfel
authors.affiliation: MS Center of Catalonia (Cemcat), Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rio
authors.affiliation: MS Center Amsterdam, Vrije University Medical Center, Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Polman
authors.affiliation: Department of Neurology, Hôpital Tenon, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Roullet
authors.affiliation: PAREXEL International GmbH, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Stolz
authors.affiliation: University Clinic of Neurology, Medical University of Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Vass
authors.affiliation: University Hospital of Schleswig-Holstein, Lübeck, Germany.
authors.forename: K P
authors.initials: KP
authors.lastname: Wandinger
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel ludwig.kappos@usb.ch.
authors.forename: L
authors.initials: L
authors.lastname: Kappos
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D000068576:Interferon beta-1b / Q000009:adverse effects / Q000627:therapeutic use*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015999:Multivariate Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D000068576:Interferon beta-1b
keywords: Disability; interferon beta; long-term outcome; magnetic resonance imaging; multiple sclerosis; neutralizing antibodies; prognosis; randomized controlled trial; secondary progressive multiple sclerosis