Introduction
Materials and methods
Patients and study design
Statistical analyses
Results
Study population
Early effects of treatment on clinical outcomes
Fingolimod 0.5 mg N = 783 | Placebo N = 773 | Fingolimod 0.5 mg N = 783 | Placebo N = 773 | |
---|---|---|---|---|
Patients free from confirmed relapse | At 3 months | At 6 months | ||
Number (%) of patients free from confirmed relapse | 717 (91.6) | 670 (86.7) | 681 (87.0) | 598 (77.4) |
Kaplan–Meier estimate of patients free from confirmed relapse, % ± SE (95 % CI) | 91.4 ± 1.0 (89.4, 93.4) | 86.4 ± 1.3 (84.0, 88.9) | 86.4 ± 1.3 (84.0, 88.9) | 76.5 ± 1.6 (73.5, 79.6) |
p value vs. placeboa
| 0.0022 | < 0.0001 | ||
Hazard ratio for fingolimod vs. placebo (95 % CI)b
| 0.64 (0.47, 0.88)
p = 0.0056 | 0.57 (0.45, 0.73)
p < 0.0001 | ||
Annualized relapse rate | Months 0–3 | Months 3–6 | ||
Number of patients | 783 | 773 | 766 | 754 |
ARR (95 % CI) | 0.32 (0.25, 0.41) | 0.52 (0.43, 0.63) | 0.21 (0.16, 0.28) | 0.45 (0.37, 0.55) |
Rate ratio vs. placebo (95 % CI)c
| 0.61 (0.45, 0.83)
p = 0.0015 | 0.47 (0.33, 0.66)
p < 0.0001 | ||
MSFC z-score | Months 0–3 | Months 0–6 | ||
Baseline (mean ± SD) | – | – | 0.08 ± 0.71 | −0.03 ± 0.92 |
Change from baseline | ||||
Mean ± SD | – | – | −0.01 ± 0.47 | −0.04 ± 0.63 |
Median (range) | – | – | 0.02 (−6.3 to 3.1) | −0.04 (−3.2 to 9.7) |
p value vs. placebod
| – | – | < 0.0001 | |
MSFC subscale: T25FW | ||||
Baseline (mean ± SD) (s) | – | – | 5.67 ± 2.64 | 6.09 ± 5.18 |
Change from baseline (s) | ||||
Mean ± SD | – | – | 0.16 ± 3.00 | 0.01 ± 4.49 |
Median (range) | – | – | 0.00 (−19.5 to 52.7) | 0.10 (−82.6 to 18.6) |
p value vs. placebod
| – | – | 0.0032 | |
MSFC subscale: 9-HPT | ||||
Baseline (mean ± SD) (s) | – | – | 21.80 ± 6.20 | 22.23 ± 6.90 |
Change from baseline (s) | ||||
Mean ± SD | – | – | 0.35 ± 5.68 | 1.04 ± 12.54 |
Median (range) | – | – | 0.05 (−32.6 to 89.4) | 0.28 (−24.3 to 289.1) |
p value vs. placebod
| – | – | 0.0041 | |
MSFC subscale: PASAT | ||||
Baseline (mean ± SD) (number of correct answers) | – | – | 48.6 ± 10.26 | 47.4 ± 11.07 |
Change from baseline (number of correct answers) | ||||
Mean ± SD | – | – | 0.6 ± 5.93 | −0.2 ± 6.43 |
Median (range) | – | – | 0 (−27 to 34) | 0 (−47 to 35) |
p value vs. placebod
| – | – | 0.0146 |
Early effects of treatment on MRI outcomes
Fingolimod 0.5 mg N = 783 | Placebo N = 773 | |
---|---|---|
Number of Gd-enhancing T1 lesions | 6 months | |
Number of patients | 726 | 698 |
Mean ± SD | 0.2 ± 0.9 | 1.2 ± 3.2 |
Median (range) | 0.0 (0–13) | 0.0 (0–43) |
Number (%) of patients free from Gd-enhancing T1 lesions | 644 (88.6) | 438 (62.4) |
p value vs. placeboa
| <0.0001 | |
Number of new/newly enlarged T2 lesions | Months 0–6 | |
Number of patients | 729 | 721 |
Mean ± SD | 0.9 ± 2.3 | 3.3 ± 7.0 |
Median (range) | 0.0 (0–28) | 1.0 (0–96) |
Number (%) of patients free from new/newly enlarged T2 lesions | 478 (65.3) | 289 (40.0) |
p value vs. placebob
| <0.0001 | |
Patients free from new MRI activity | At 6 months | |
Number (%) of patients free from new MRI activityc
| 475 (65.3) | 284 (40.5) |
p value vs. placeboa
| <0.0001 | |
Brain volume loss | At 6 months | |
Number of patients | 714 | 709 |
Mean PBVC from baseline | −0.23 | −0.36 |
Reduction vs. placebo (%) | 37.1 | |
p value vs. placebod
| <0.001 |