Table 1.
Supportive and sensitivity analyses of primary end points at end of study (up to Month 24)*
| Fingolimod (n=107) |
Interferon β-1a (n=107) |
Rate ratio or between-group difference (95% CI) | Rate reduction | P value | |
| Estimated annualised relapse rate (95% CI)† | |||||
| FAS | 0.12 (0.08 to 0.19) | 0.67 (0.52 to 0.89) | 0.18 (0.11 to 0.30) | 81.9% | <0.001 |
| Excluding data after SDD | 0.12 (0.08 to 0.20) | 0.73 (0.55 to 0.96) | 0.17 (0.10 to 0.29) | 83.1% | <0.001 |
| PPS | N’=96 0.12 (0.07 to 0.20) |
N’=101 0.72 (0.53 to 0.97) |
0.17 (0.10 to 0.30) | 83.2% | <0.001 |
| Excluding IFN NAbs-positive patients | N’=107 0.12 (0.08 to 0.20) |
N’=98 0.67 (0.50 to 0.89) |
0.19 (0.11 to 0.31) | 81.5% | <0.001 |
| Treatment-naïve patients | N’=69 0.07 (0.04 to 0.15) |
N’=67 0.50 (0.34 to 0.74) |
0.14 (0.06 to 0.32) | 85.8% | <0.001 |
| Observed annualised relapse rate | |||||
| Patients ≤12 years | N’=13 0.10 |
N’=9 0.72 |
See model | ||
| Prepubertal patients | N’=7 0.20 |
N’=3 1.49 |
See model | ||
| Pubertal patients | N’=98 0.13 |
N’=104 0.73 |
See model | ||
| Model-based annualised relapse rate based on extrapolation from all paediatric patients (95% CI) | |||||
| Younger patients‡ | |||||
| Overall FAS | 0.12 (0.07 to 0.19) | 0.73 (0.56 to 0.97) | 0.16 (0.1 to 0.28) | 83.8% | <0.001 |
| 10 years | 0.04 (0.01 to 0.21) | 0.76 (0.29 to 2.03) | 0.05 (0.01 to 0.36) | 94.6% | 0.003 |
| 11 years | 0.05 (0.01 to 0.20) | 0.76 (0.33 to 1.71) | 0.07 (0.01 to 0.33) | 93.4% | <0.001 |
| 12 years | 0.06 (0.02 to 0.19) | 0.75 (0.39 to 1.44) | 0.08 (0.02 to 0.30) | 91.9% | <0.001 |
| Prepubertal patients§ | N’=7 | N’=3 | Pos-Prob¶: | ||
| 0.16 (0.00 to 0.89) | 1.97 (0.20 to 10.53) | 0.26 (0.00 to 1.82) | 73.9% | 93.8% | |
| Pubertal patients | N’=98 | N’=104 | |||
| 0.08 (0.04 to 0.15) | 0.72 (0.54 to 0.96) | 0.12 (0.05 to 0.22) | 88.2% | 100.0% | |
| All relapses (confirmed and unconfirmed) | |||||
| FAS | FAS 0.18 (0.13 to 0.26) | 0.80 (0.64 to 1.01) | 0.23 (0.15 to 0.35) | 77.4% | <0.001 |
| PPS | N’=96 0.17 (0.11 to 0.26) |
N’=101 0.81 (0.63 to 1.04) |
0.21 (0.13 to 0.34) | 78.6% | <0.001 |
End of study defined as the last assessment taken on or before the final study phase visit date.
*Unless otherwise stated.
†Between-treatment comparison obtained from fitting a negative binomial regression model adjusted as described in methodology.
‡Estimated at a given age at baseline by fitting a negative binomial regression model adjusted for treatment, age at baseline, region, pubertal status (stratified variable), number of relapses within the previous 2 years before randomisation as well as age and treatment interaction.
§Obtained from fitting a Bayesian-negative binomial regression model with mixture priors adjusted for treatment, age, number of relapses within the previous 2 years before randomisation as well as age and treatment interaction.
¶Pos-Prob indicates the posterior probability of the rate ratio is <1, ie, the probability of the ARR with fingolimod being lower than the ARR with IFN β-1a.
ARR, annualised relapse rate; FAS, full analysis set; IFN, interferon; N’, total number of subjects with available result and included in the analysis; NAbs, neutralising antibodies; PPS, per-protocol set; SDD, study drug discontinuation.