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

• Published in: Neurology Vol. 78; no. 17; pp. 1315 - 1322
• Main Authors: GOODIN, D. S, REDER, A. T, KNAPPERTZ, V, EBERS, G. C, CUTTER, G, KREMENCHUTZKY, M, OGER, J, LANGDON, D, RAMETTA, M, BECKMANN, K, DESIMONE, T. M
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 24-04-2012
• Subjects: Adjuvants, Immunologic - therapeutic use; Adult; Age of Onset; Biological and medical sciences; Cause of Death; Female; Humans; Interferon beta-1b; Interferon-beta - therapeutic use; Kaplan-Meier Estimate; Male; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - mortality; Neurology; Survival Analysis; Survival; Nervous system diseases; Cohort study
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/WNL.0b013e3182535cf6

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.
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.
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.
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.
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.