Analysis of the primary efficacy endpoint
Fatigue as measured by the change from baseline estimate in FSMC total score showed a significant improvement (p<0.0001) at month 12, with a mean reduction of 9.0 (95% CI −11.2, −6.8) from a baseline mean score of 71.2 (Table 3, Fig. 2). At a population-level this improvement reduced fatigue qualitatively from severe at baseline to moderate at month 12. We regard a mean total score reduction of 9 as clinically meaningful.
10.1371/journal.pone.0058643.g002 Figure 2  Patient reported fatigue at base line and during the 12 months of natalizumab treatment.
A validated questionnaire for MS, the Fatigue Scale for Motor and Cognitive functions (FSMC) allowing separate evaluations of motor and cognitive aspects of fatigue, was used. The total, motor and cognitive FSMC score at base line and month 3, 6, 9 and 12 are shown. Error bars = Standard Error of the Mean.
10.1371/journal.pone.0058643.t003 Table 3  Primary end point results: Fatigue as measured by the FSMC; total, motor and cognitive scores and mean change from baseline to month 12 for the ITT population.     FSMC: The Fatigue Scale for Motor and Cognitive functions, CI: Confidence Interval.

A