Survival in MS A randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial

Objective: To examine the effects of interferon beta (IFN beta)-1b on all-cause mortality over 21 years in the cohort of 372 patients who participated in the pivotal randomized clinical trial (RCT), retaining (in the analysis) the original randomized treatment-assignments. Methods: For this randomized long-term cohort study, the primary outcome, defined before data collection, was the comparison of all-cause mortality between the IFN beta-1b 250 mu g and placebo groups from the time of randomization through the entire 21-year follow-up interval (intention-to-treat, log-rank test for Kaplan-Meier survival curves). All other survival outcomes were secondary. Results: After a median of 21.1 years from RCT enrollment, 98.4% (366 of 372) of patients were identified, and, of these, 81 deaths were recorded (22.1% [81 of 366]). Patients originally randomly assigned to IFN beta-1b 250 mu g showed a significant reduction in all-cause mortality over the 21-year period compared with placebo (p = 0.0173), with a hazard ratio of 0.532 (95% confidence interval 0.314-0.902). The hazard rate of death at long-term follow-up by Kaplan-Meier estimates was reduced by 46.8% among IFN beta-1b 250 mu g-treated patients (46.0% among IFN beta-1b 50 mu g-treated patients) compared with placebo. Baseline variables did not influence the observed treatment effect. Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFN beta-1b treatment at either dose compared with placebo. Near-complete ascertainment, together with confirmatory findings from both active treatment groups, strengthens the evidence for an IFN beta-1b benefit on all-cause mortality. Classification of Evidence: This study provides Class III evidence that early treatment with IFN beta-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis. Neurology (R) 2012; 78: 1315-1322