Table 1.
Summary of selected outcomes in phase II and III placebo-controlled teriflunomide studies.
| Phase II [ClinicalTrials.gov identifier: NCT01487096]24 |
TEMSO [ClinicalTrials.gov identifier: NCT00134563] 25 |
TOWER [ClinicalTrials.gov identifier: NCT00751881]26 |
TOPIC [ClinicalTrials.gov identifier: NCT00622700]27 |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Study duration: 36 weeks |
Study duration: 108 weeks |
Study duration: variable (48 weeks after the last patient was randomized) |
Study duration: ⩽108 weeks |
|||||||||
| Placebo | Teriflunomide |
Placebo | Teriflunomide |
Placebo | Teriflunomide |
Placebo | Teriflunomide |
|||||
| 7 mg | 14 mg | 7 mg | 14 mg | 7 mg | 14 mg | 7 mg | 14 mg | |||||
| Patients entering study, n | 61 | 61 | 57 | 363 | 365 | 358 | 388 | 407 | 370 | 197 | 203 | 214 |
| Clinical endpoints | ||||||||||||
| ARR | 0.81 | 0.58 | 0.55 | 0.54 | 0.37 | 0.37 | 0.50 | 0.39 | 0.32 | 0.284 | 0.190 | 0.194 |
| Relative risk reduction (versus control), % | 28 | 32 | 31.2 | 31.5 | 22.3 | 36.3 | 33.1 | 31.9 | ||||
| p value | NS | NS | p < 0.001 | p < 0.001 | p = 0.018 | p = 0.0001 | p = 0.054 | p = 0.058 | ||||
| Patients relapse free,*$ % | 62 | NR | 77 | 45.6 | 53.7 | 56.5 | 60.6 | 71.9 | 76.3 | – | – | – |
| p value (versus control) | p = 0.098 | p = 0.01 | p = 0.003 | p = 0.002 | p < 0.001 | |||||||
| Disability endpoints | ||||||||||||
| Patients with 12-week CDW,‡ % | 27.3 | 21.7 | 20.2 | 19.7 | 21.1 | 15.8 | 10§ | 10§ | 7§ | |||
| Risk reduction (versus placebo), % | 23.7 | 29.8 | 4.5 | 31.5 | 2.2 | 29.9 | ||||||
| p value (versus placebo) | p = 0.08 | p = 0.03 | p = 0.762 | p = 0.044 | p = 0.995 | p = 0.424 | ||||||
| Patients with increased EDSS score at endpoint versus baseline, % | 7.4 | – | 21.3 | |||||||||
| p value (versus placebo) | p < 0.04 | |||||||||||
| Change in EDSS score from baseline, mean | – | – | – | – | – | – | 0.09 | 0.04 | –0.05 | –0.056 | –0.250 | –0.265 |
| p value (versus placebo) | p = 0.482 | p = 0.043 | p = 0.033 | p = 0.044 | ||||||||
| MRI endpoints | ||||||||||||
| Change in total lesion volume from baseline, mean, ml | 2.21 | 1.31 | 0.72 | – | – | – | 0.044 | 0.023 | –0.028 | |||
| Relative reduction (versus placebo), % | 39.4 | 67.4 | – | – | ||||||||
| p value | p = 0.03 | p < 0.001 | p = 0.779 | p = 0.037 | ||||||||
| Gd-enhancing T1 lesions per scan, mean, n | 2.25 | 0.87 | 0.32 | 1.33 | 0.57 | 0.26 | 0.953 | 0.749 | 0.395 | |||
| Difference, mean | −1.38 | −1.39 | – | – | – | |||||||
| Relative risk | NR | NR | 0.43 | 0.20 | 21.4 | 58.5 | ||||||
| p value (versus placebo) | p < 0.04 | p < 0.02 | p < 0.001 | p < 0.001 | p = 0.444 | p = 0.001 | ||||||
| CU active lesions per scan, mean, n | 2.68 | 1.04 | 1.06 | 2.46 | 1.29 | 0.75 | ||||||
| Relative reduction, % | 61 | 61 | 69 | 48 | – | – | – | – | – | – | ||
| Relative risk | NR | NR | 0.52 | 0.31 | ||||||||
| p value (versus placebo) | p < 0.03 | p < 0.01 | p < 0.001 | p < 0.001 | ||||||||
*
In TEMSO and TOWER, defined as free from protocol-defined relapse at 48 weeks.
$
In TOPIC, a relapse was defined as a new neurologic abnormality separated by at least 30 days from a preceding clinical event, present for at least 24 h in the absence of fever or known infection.
‡
Values in TOWER are those after 108 weeks of treatment.
§
Patients presenting with a first episode suggestive of MS do not have prolonged disease.
ARR, annualized relapse rate; CDW, confirmed disability worsening; CU, combined unique; EDSS, Expanded Disability Status Scale; Gd, gadolinium; MS, multiple sclerosis; NR, not recorded; NS, not significant.