title: Multiple sclerosis relapses are associated with increased fatigue and reduced health-related quality of life - A post hoc analysis of the TEMSO and TOWER studies.
abstract: BACKGROUND
  Two pivotal phase 3 teriflunomide studies provided data on relapses, fatigue, and health-related quality of life (HRQoL) in patients with relapsing forms of multiple sclerosis (MS).
  
  
  OBJECTIVE
  Using pooled data from the TEMSO (NCT00134563) and TOWER (NCT00751881) studies, we investigated the association between relapse severity, and changes from baseline to Week 108 in fatigue and HRQoL outcomes.
  
  
  METHODS
  Four definitions of relapse severity were applied in this analysis: sequelae post-relapse; relapse leading to hospitalization; relapse requiring intravenous corticosteroids; and intense relapse. We assessed the association between relapse severity and changes in Fatigue Impact Scale score (n=959), physical and mental health component summary scores from the Short Form (SF)-36 questionnaire (n=904), and SF-6D utility index scores (n=820).
  
  
  RESULTS
  Irrespective of the definition of relapse severity applied, in patients experiencing severe relapse(s), fatigue was increased and HRQoL was decreased; these changes were statistically significant (p<0.0001), and were also clinically significant in many cases. The greatest worsening in fatigue and HRQoL was observed in patients with relapses leading to hospitalization.
  
  
  CONCLUSIONS
  Given that severe relapses adversely affect patient-reported fatigue and HRQoL, prevention of severe relapses should be an important therapeutic aim in the treatment of patients with MS.
authors.affiliation: Klinik für Neurologie, Caritas Krankenhaus Bad Mergentheim, Uhlandstraße 7, 97980 Bad Mergentheim, Germany. Electronic address: mathias.maeurer@ckbm.de.
authors.forename: Mathias
authors.initials: M
authors.lastname: Mäurer
authors.affiliation: Department of Neurology and Institute of Experimental Neurology, University Vita-Salute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Electronic address: comi.giancarlo@hsr.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: University of Ottawa and the Ottawa Hospital Research Institute, The Ottawa Hospital - General Campus, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6. Electronic address: mfreedman@toh.on.ca.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Freedman
authors.affiliation: Neurology, Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. Electronic address: lkappos@uhbs.ch.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neurosciences, Karolinska Hospital, CMM L8:04, 17176 Stockholm, Sweden. Electronic address: tomas.olsson@ki.se.
authors.forename: Tomas P
authors.initials: TP
authors.lastname: Olsson
authors.affiliation: Department of Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA. Electronic address: jerry.s.wolinsky@uth.tmc.edu.
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Wolinsky
authors.affiliation: Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, Box 1138, New York, NY 10029, USA. Electronic address: aaron.miller@mssm.edu.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Miller
authors.affiliation: Health Economics/Outcomes Research, Sanofi Genzyme, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin, France. Electronic address: catherine.dive-pouletty@sanofi.com.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dive-Pouletty
authors.affiliation: Health Economics/Outcomes Research, Sanofi Genzyme, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin, France. Electronic address: sylvie.bozzi@sanofi.com.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bozzi
authors.affiliation: St Michael's Hospital, Division of Neurology, 30 Bond Street, Toronto, ON, Canada M5B 1W8. Electronic address: oconnorp@smh.ca.
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Connor
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D003437:Crotonates / Q000627:therapeutic use; D005221:Fatigue / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates; D007155:Immunologic Factors / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology* / Q000523:psychology*; D009570:Nitriles; D011788:Quality of Life; D012008:Recurrence; D012720:Severity of Illness Index; D014052:Toluidines / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D003437:Crotonates; D006885:Hydroxybutyrates; D007155:Immunologic Factors; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide
keywords: FIS; Fatigue; Multiple sclerosis; Quality of life; Relapse; SF-36; Sequelae; Teriflunomide