Survival in MS
A randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial
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Abstract
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.
GLOSSARY
- 16Y-LTF=
- 16-Year Long-Term Follow-Up;
- 21Y-LTF=
- 21-Year Long-Term Follow-Up;
- BOD=
- burden of disease;
- CI=
- confidence interval;
- DMT=
- disease-modifying therapy;
- EDSS=
- Expanded Disability Status Scale;
- HR=
- hazard ratio;
- IFNβ-1b=
- interferon β-1b;
- MS=
- multiple sclerosis;
- RCT=
- randomized clinical trial
Footnotes
Study funding: Funding information is provided at the end of the article.
Supplemental data at www.neurology.org
- Received June 8, 2011.
- Accepted December 14, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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