Table 1.
Summary of clinical and MRI endpoints over 2 years by original randomization group.
| Endpoint | Delayed treatmenth (n=500) | Peginterferon beta-1a every 2 weeks (n=512) | Peginterferon beta-1a every 4 weeks (n=500) |
|---|---|---|---|
| Annualized relapse rate at 2 years | |||
| Annualized relapse rate (95% CI)a | 0.351 (0.295, 0.418) | 0.221 (0.183, 0.267) | 0.291 (0.244, 0.348) |
| Rate ratio vs. delayed treatment (95% CI)a | 0.629 (0.500, 0.790) | 0.829 (0.666, 1.030) | |
| p-value vs. delayed treatmenta | <0.0001 | 0.0906 | |
| Rate ratio every 2 weeks vs. every 4 weeks (95% CI)a | 0.759 (0.600, 0.959) | ||
| p-value (every 2 weeks vs. every 4 weeks)a | 0.0209 | ||
| Estimated proportion of patients with a relapse at 2 years | |||
| Number of patients relapsed | 192 | 124 | 158 |
| Proportion relapsedb | 0.402 | 0.265 | 0.344 |
| Hazard ratio vs. delayed treatmentc | 0.61 (0.49, 0.76) | 0.81 (0.65, 1.00) | |
| p-value vs. delayed treatmentc | <0.0001 | 0.0465 | |
| Hazard ratio every 2 weeks vs. every 4 weeks (95% CI)c | 0.76 (0.60, 0.96) | ||
| p-value (every 2 weeks vs. every 4 weeks)c | 0.0212 | ||
| Disability progression at 2 years (12-week confirmed) | |||
| Number of patients with disability progression | 75 | 51 | 56 |
| Estimated proportion with disability progressiond | 0.162 | 0.112 | 0.123 |
| Hazard ratio vs. delayed treatment (95% CI)e | 0.67 (0.47, 0.95) | 0.75 (0.53, 1.05) | |
| p-value vs. delayed treatmente | 0.0257 | 0.0960 | |
| Hazard ratio every 2 weeks vs. every 4 weeks (95% CI)e | 0.89 (0.61, 1.31) | ||
| p-value (every 2 weeks vs. every 4 weeks)e | 0.5665 | ||
| Disability progression at 2 years (24-week confirmed) | |||
| Number of patients with disability progression | 57 | 34 | 52 |
| Estimated proportion with disability progressiond | 0.119 | 0.077 | 0.113 |
| Hazard ratio vs. delayed treatment (95% CI)e | 0.59 (0.38, 0.90) | 0.91 (0.63, 1.33) | |
| p-value vs. delayed treatmente | 0.0137 | 0.6243 | |
| Hazard ratio every 2 weeks vs. every 4 weeks (95% CI)e | 0.64 (0.42, 0.99) | ||
| p-value (every 2 weeks vs. every 4 weeks)e | 0.0459 | ||
| New or newly enlarging T2-weighted hyperintense lesions at 2 years | |||
| Number of patients evaluated | 393 | 407 | 389 |
| Adjusted mean number of lesionsf | 14.8 | 5.0 | 12.5 |
| Lesion mean ratio (peginterferon beta-1a:delayed treatment) (95% CI)f | 0.33 (0.27, 0.41) | 0.84 (0.69. 1.03) | |
| p-value (peginterferon beta-1a:delayed treatment)f | <0.0001 | 0.0973 | |
| Lesion mean ratio (every 2 weeks:every 4 weeks) (95% CI)f | 0.40 (0.32, 0.49) | ||
| p-value (every 2 weeks vs. every 4 weeks)f | <0.0001 | ||
| Gd+ lesions at 2 years | |||
| Number of patients evaluated | 393 | 407 | 389 |
| Mean number of lesions (SE) | 0.5 (0.08) | 0.2 (0.06) | 0.7 (0.12) |
| p-value (peginterferon beta-1a vs. delayed treatment)g | 0.0002 | 0.2169 | |
| Percent reduction (every 2 weeks vs. every 4 weeks)g | 71 | ||
| p-value (every 2 weeks vs. every 4 weeks)g | <0.0001 | ||
Based on negative binomial regression, with adjustment for baseline EDSS (<4 vs. ≥4), baseline relapse rate, age (<40 vs. ≥40).
Based on Kaplan–Meier product limit method.
Based on Cox proportion hazards model, adjusted for baseline EDSS (<4 vs. ≥4), age (<40 vs. ≥40), baseline relapse rate, and baseline Gd+ lesions (presence vs. absence).
Estimated proportion of patients with progression based on the Kaplan–Meier product limit method.
Based on Cox proportional hazards model, adjusted for baseline EDSS and age (<40 vs. ≥40).
Based on negative binomial regression, adjusted for baseline number of new or newly enlarging T2 lesions.
Percent reduction based on group mean and p-value based on multiple logit regression, adjusted for baseline number of Gd+ lesions.
Delayed treatment group: Patients who received placebo in Year 1 and switched to peginterferon beta-1a in Year 2.