RT Journal Article
SR Electronic
T1 Survival in MS
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP WNL.0b013e3182535cf6
DO 10.1212/WNL.0b013e3182535cf6
A1 D.S. Goodin
A1 A.T. Reder
A1 G.C. Ebers
A1 G. Cutter
A1 M. Kremenchutzky
A1 J. Oger
A1 D. Langdon
A1 M. Rametta
A1 K. Beckmann
A1 T.M. DeSimone
A1 V. Knappertz
YR 2012
UL http://n.neurology.org/content/early/2012/04/11/WNL.0b013e3182535cf6.abstract
AB Objective: To examine the effects of interferon beta (IFNβ)-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 IFNβ-1b 250 μg 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 IFNβ-1b 250 μg 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 IFNβ-1b 250 μg–treated patients (46.0% among IFNβ-1b 50 μg–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 IFNβ-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 IFNβ-1b benefit on all-cause mortality. Classification of Evidence: This study provides Class III evidence that early treatment with IFNβ-1b is associated with prolonged survival in initially treatment-naive patients with relapsing-remitting multiple sclerosis.