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

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 EDSS score or Functional System scores.

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).

All randomized and treated participants; Participants were included in the treatment group to which they were originally assigned (intent-to-treat analysis).

12-week sustained disability progression was defined as an increase from baseline of at least 1-point in EDSS score (at least 0.5-point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks.

Probability of disability progression at 24, 48 and 108 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase. Participants free of disability progression (no disability progression observed on treatment) were censored at the date of the last on-treatment EDSS evaluation.

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.

All randomized and treated participants; Participants were included in the treatment group to which they were originally assigned (intent-to-treat analysis).

Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis.

All randomized and treated participants; Participants were included in the treatment group to which they were originally assigned (intent-to-treat analysis).

Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.

To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as "offset" variable; treatment group, region of enrollment, baseline EDSS stratum and baseline number of Gd-enhancing T1-lesions as covariates).

All randomized and treated participants; Participants were included in the treatment group to which they were originally assigned (intent-to-treat analysis).

Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.

All randomized and treated participants; Participants were included in the treatment group to which they were originally assigned (intent-to-treat analysis).

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).

All randomized and treated participants; Participants were included in the treatment group to which they were originally assigned (intent-to-treat analysis).