Table 1. Definitions of disease activity used in the analysis.

MRI
Intermittent“yes” if there is any new or enlarging T2/FLAIR lesion or gadolinium lesion at any time including baseline, otherwise “no”
Progression 1“yes” if brain parenchymal fraction measurement at 24 months is lower than baseline by at least 1 SD, otherwise “no”
Progression 2“yes” if brain parenchymal fraction measurement at 24 months is lower than baseline by at least 0.5 SD, otherwise “no”
Progression 3“yes” if brain parenchymal fraction measurement at 24 months is lower than baseline by at least 0.25 SD, otherwise “no”
EDSS Total Score
Intermittent“yes” if there is any increase in score comparing to the prior measurement of at least X point followed by any decrease in next 6 months (either after 3 M or 6 M) (X  = 1 if baseline EDSS < = 5.5; X  = 0.5 if baseline EDSS > = 6), otherwise “no”
Progression 1“yes” if there is any increase in score comparing to the baseline of at least X point and there is no decrease after that (can stay stable or increase further) (X  = 1 if baseline EDSS < = 5.5; X  = 0.5 if baseline EDSS > = 6), otherwise “no”
Progression 2“yes” if (score of any time point - score at baseline) are positive for X number of times (X > = 5, 6, 7, or 8 out of 8), otherwise “no”
Improvement“yes” if both scores of the last 2 visits are smaller than baseline by at least X point (X  = 1 if baseline EDSS < = 5.5; X  = 0.5 if baseline EDSS > = 6), otherwise “no”
EDSS Sub-System Scores
Intermittent“yes” if there is any increase in score of at least 2 point compared to prior measurement followed by any decrease in next 6 months (either after 3 M or 6 M), otherwise “no”
Progression 1“yes” if there is any increase in score comparing to the baseline of at least 1 point and there is no decrease after that (can stay stable or increase), otherwise “no”
Progression 2“yes” if (score of any time point - score at baseline) are positive for X times (X > = 5, 6, 7, or 8 out of 8 visits), otherwise “no”
Improvement“yes” if both scores of the last 2 visits are smaller than baseline by at least 1 point, otherwise “no”
MSFC components (note: PASAT has different direction)
Intermittent“yes” if there is any increase in time compared to the prior measurement of at least 20% followed by any decrease over the following 6 months (either after 3 M or 6 M), otherwise “no”
Progression 1“yes” if there is any increase in time compared to the baseline of least 20% and there is no decrease after that (can stay stable or increase), otherwise “no”
Progression 2“yes” if (time of any time point - time at baseline) are positive for X number of times (X > = 5, 6, 7, or 8 out of 8 visits), otherwise “no”
Improvement“yes” if both times of the last two study visits are smaller than baseline by at least 20%, otherwise “no”
MSQLI
Progression“yes” if at least two scores at (month 15 and month 24) are lower than baseline, otherwise “no”
Improvement“yes” if at least two scores at (month 15 and month 24) are higher than baseline, otherwise “no”