A Study Comparing the Effectiveness and Safety of Teriflunomide and Interferon Beta-1a in Patients With Relapsing Multiple Sclerosis (TENERE)

• Overview of Failures [ Time Frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled ] [ Designated as safety issue: No ]

  Failure was defined as the first occurence of confirmed relapse or permanent treatment discontinuation (for any cause) which ever came first. If no events occurred, the participant was considered free of failure.

  Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores.

  
  
• Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints [ Time Frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled ] [ Designated as safety issue: No ]

  Probability of disability progression at 24, 48 and 96 weeks was estimated using Kaplan-Meier method on the time to failure defined as the time from randomization to failure. Participants free of failure were censored at the date of last treatment.

  Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.

  
  

• Annualized Relapse Rate [ARR]: Poisson Regression Estimates [ Time Frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled ] [ Designated as safety issue: No ]

  ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.

  To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and baseline EDSS stratum as covariates).

  
  
• Change From Baseline in Fatigue Impact Scale (FIS) Total Score [ Time Frame: baseline (before randomization) and 48 weeks ] [ Designated as safety issue: No ]

  FIS is a subject-reported scale that qualifies the impact of fatigue on daily life in patients with MS. It consists of 40 statements that measure fatigue in three areas; physical, cognitive, and social.

  FIS total score ranges from 0 (no problem) to 160 (extreme problem).

  Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors).

  
  
• Treatment Satisfaction Questionnaire for Medication [TSQM] Scores [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

  TSQM version 1.4 is an instrument to assess patients' satisfaction with medication. It consists of 13 questions that cover three dimensions (effectiveness, side effects and convenience) plus a global satisfaction question.

  Four scores ranging from 0 to 100 (extremely satisfied) are obtained.

  Least-square means were estimated using a Mixed-effect model with repeated measures [MMRM] on TSQM score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction as factors).

  
  
• Overview of Adverse Events [AE] [ Time Frame: from first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first ] [ Designated as safety issue: Yes ]
  AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
  
  

The core treatment period per participant was variable depending on the enrollment in the study (maximum of approximatively 118 weeks). The two doses of teriflunomide were administered in double-blind fashion, whereas interferon beta-1a (Rebif®) was open-label.

The opportunity to continue with the highest dose of teriflunomide in open-label fashion was offered to the participants who successfully completed treatment in the core study.

The overall treatment period was followed by a 4-week elimination follow-up period.