title: Effect of switching from intramuscular interferon β-1a to oral fingolimod on time to relapse in patients with relapsing-remitting multiple sclerosis enrolled in a 1-year extension of TRANSFORMS.
abstract: BACKGROUND
  In the absence of controlled, parallel-group studies, statistical methods developed to estimate treatment effects in patients receiving alternative/rescue treatment in clinical trials may be used to estimate the effects of multiple sclerosis (MS) therapy switch using available clinical trial data.
  
  
  OBJECTIVE
  To use TRANSFORMS data and parametric models to assess the time to first confirmed relapse in MS patients who switched from intramuscular interferon β-1a (IFNβ-1a IM) 30 μg/mL once weekly to oral fingolimod 0.5 or 1.25mg once daily vs. remaining on IFNβ-1a IM.
  
  
  METHODS
  Post hoc analyses were conducted using data from the intent-to-treat population. The Branson and Whitehead switch model with iterative parameter estimation was used to estimate the ratio of the observed time to first confirmed relapse over the estimated time.
  
  
  RESULTS
  Log-linear regression model results showed that fingolimod 0.5 and 1.25mg prolonged time to relapse, with an estimated median time to first relapse of 5.07 years (P=0.0026 vs. IFNβ-1a IM) and 4.11 years (P=0.0113), respectively, versus 2.26 years with IFNβ-1a IM. The estimated ratio of observed time to first confirmed relapse to the estimated time had the patient remained on IFNβ-1a IM was 2.09 (95% CI, 1.45-3.04) for switching to fingolimod 0.5mg and 1.84 (95% CI, 1.30-2.65) for switching to fingolimod 1.25mg.
  
  
  CONCLUSIONS
  During the extension, time to first confirmed relapse was approximately doubled in patients switching from IFNβ-1a IM to fingolimod. These analytic methods may be useful in evaluating treatment switch effects in clinical trials with extension data.
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: xiangyi.meng@novartis.com.
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Meng
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: Peter.chin@novartis.com.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Chin
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: Ronny.hashmonay@novartis.com.
authors.forename: Ron
authors.initials: R
authors.lastname: Hashmonay
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936-1080, United States. Electronic address: zahur.islam@novartis.com.
authors.forename: M
authors.initials: M
authors.lastname: Zahur Islam
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham School of Public Health, Birmingham, AL 35294-0022, United States. Electronic address: cutterg@prodigy.net.
authors.forename: Gary
authors.initials: G
authors.lastname: Cutter
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D057915:Drug Substitution; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride; D000068556:Interferon beta-1a
keywords: Disease modifying therapy; Fingolimod; Interferon beta; Modeling; Multiple sclerosis; Relapse; Treatment switch