title: Canadian treatment optimization recommendations (TOR) as a predictor of disease breakthrough in patients with multiple sclerosis treated with interferon beta-1a: analysis of the PRISMS study.
abstract: BACKGROUND
  Early intervention with an effective disease-modifying drug (DMD) offers the best chance of limiting the inflammatory process that contributes to irreversible axonal damage correlating with disability in multiple sclerosis (MS). It is equally important to ascertain fairly quickly whether patients are responding positively to the choice of therapy to allow time for either a treatment modification or a switch in treatment, a process we termed "treatment optimization". Various treatment optimization recommendations (TOR) have been proposed to help decide when a patient taking an MS DMD might be showing a sub-optimal response. We have applied the clinical scheme proposed by the Canadian TOR to the patients involved in the Prevention of Relapses and disability by Interferon Subcutaneously in MS 4-year (PRISMS-4) study, who received interferon beta-1a treatment for 4 years, with the TOR applied retrospectively at year 1.
  
  
  OBJECTIVE
  The aim of this investigation was to examine whether these TOR were able to predict which patients would go on to develop disease breakthrough (defined as any relapses or disease progression), indicative of a sub-optimal response over the ensuing 3 years of study and therefore might have benefited from a change in treatment.
  
  
  RESULTS
  We found 39% of patients receiving therapy experienced either a medium or high level of concern of breakthrough after a year of treatment, and 89% of these patients went on to develop further breakthrough over years 2-4. Although 67% of the 61% of patients having no or low-level concern after a year of treatment also experienced further disease breakthrough, it was significantly less than the medium or high group.
  
  
  CONCLUSIONS
  This study shows that the Canadian TOR may be an important tool for early treatment optimization.
authors.affiliation: Department of Medicine (Neurology), University of Ottawa, Ottawa, Ontario, Canada. mfreedman@ottawahospital.on.ca
authors.forename: M S
authors.initials: MS
authors.lastname: Freedman
authors.forename: F G
authors.initials: FG
authors.lastname: Forrestal
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D002170:Canada; D017326:Clinical Trials, Phase III as Topic; D016208:Databases, Factual; D018450:Disease Progression; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology*; D010919:Placebos; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D055502:Secondary Prevention
chemical_list: D000276:Adjuvants, Immunologic; D010919:Placebos; D016899:Interferon-beta; D000068556:Interferon beta-1a