Table 2. Summary of Efficacy Results in the Full Analysis Set.
| End point from baseline to week 108 | Ponesimod, 20 mg (n = 567) | Patients included in analysis, No. | Teriflunomide, 14 mg (n = 566) | Patients included in analysis, No. | RR (99% CL) or Difference, RR, or HR (95% CL) | P value |
|---|---|---|---|---|---|---|
| Primary end point | ||||||
| Mean annualized relapse rate/y (95% CL)a | 0.202 (0.173-0.235) | 567 | 0.290 (0.254-0.331) | 566 | 0.695 (0.536-0.902)b | <.001 |
| Secondary end points | ||||||
| LS mean FSIQ-RMS weekly symptoms score change (95% CL)c | −0.01 (−1.60 to 1.58) | 449 | 3.56 (1.96-5.16) | 458 | −3.57 (−5.83 to −1.32)d | .002 |
| Mean cumulative combined unique active lesions/y (95% CL)e | 1.405 (1.215-1.624) | 539 | 3.164 (2.757-3.631) | 536 | 0.444 (0.36-0.54)f | <.001 |
| Patients with first 12-wk confirmed disability accumulation, No. (%)g | 57 (10.1) | 567 | 70 (12.4) | 566 | 0.83 (0.58-1.18)h | .29 |
| Exploratory end points | ||||||
| Patients with first 24-wk confirmed disability accumulation, No. (%)g | 46 (8.1) | 567 | 56 (9.9) | 566 | 0.84 (0.57 to 1.24)h | .37 |
| Mean cumulative new gadolinium-enhancing T1 lesions/scan (95% CL) | 0.18 (0.141-0.224) | 540 | 0.43 (0.351-0.525) | 538 | 0.42 (0.31-0.56)f | <.001 |
| LS mean change in brain volume, % (95% CL)i | −0.91 (−1.03 to −0.79) | 436 | −1.25 (−1.36 to −1.13) | 434 | 0.34 (0.17 to 0.50)d | <.001 |
| Estimated mean NEDA-3, % (95% CL)i | 25.0 (21.4-29.0) | 564 | 16.4 (13.5-19.8) | 558 | 1.70 (1.27 to 2.28)j | <.001 |
| Estimated mean NEDA-4, % (95% CL)k | 11.4 (8.7-14.6) | 526 | 6.5 (4.7-9.0) | 532 | 1.85 (1.24-2.76)j | .003 |
Abbreviations: CL, confidence limit; DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; FSIQ-RMS, Fatigue Symptom and Impact Questionnaire–Relapsing Multiple Sclerosis; HR, hazard ratio; LS, least squares; NEDA, no evidence of disease activity; OR, odds ratio; RR, rate ratio.
Confirmed relapses up to the end of the study; a negative binomial model was applied with Wald CLs and P value, the offset log time (years) to the end of the study, and covariates of EDSS strata (≤3.5 or >3.5), DMT in the last 2 years prior to randomization strata, and the number of relapses in the year prior study entry (≤1 or ≥2).
RR (99% CL).
Mixed-effects, repeated-measurements model with unstructured covariance, treatment, visit, treatment by visit interaction, baseline by visit interaction as fixed effects, baseline FSIQ-RMS score, EDSS strata (≤3.5 or >3.5), and DMT in the 2 years prior to randomization as covariates. A negative change from baseline indicates an improvement in fatigue symptoms.
Difference (95% CL).
Negative binomial model was applied with Wald 95% CIs, a P value, and an offset of log time (years) up to last magnetic resonance imaging scan and covariates of EDSS strata (≤3.5 or >3.5), DMT within the 2 years prior to randomization, and gadolinium-enhancing T1 lesions at baseline.
RR (95% CL).
Change from baseline to end of study; stratified by EDSS category and DMT within 2 years, Cox regression with 95% Wald CLs and a log-rank P value.
HR (95% CL).
Mixed model with linear time effect and covariates of EDSS strata (≤3.5 or >3.5), DMT within the 2 years prior to randomization strata, gadolinium-enhancing T1 lesions at baseline, and baseline brain volume.
OR (95% CL).
Logistic regression with treatment as factor, adjusted for covariates EDSS strata (≤3.5 or >3.5), DMT in the 2 years prior to randomization, the number of relapses in the year prior to study entry (≤1 or ≥2), and the presence of gadolinium-enhancing T1 lesions at baseline.