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.
RCT Entities:
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.
Authors: G C Ebers; A Traboulsee; D Li; D Langdon; A T Reder; D S Goodin; T Bogumil; K Beckmann; C Wolf; A Konieczny Journal: J Neurol Neurosurg Psychiatry Date: 2010-06-19 Impact factor: 10.154
Authors: L Kappos; A Traboulsee; C Constantinescu; J-P Erälinna; F Forrestal; P Jongen; J Pollard; M Sandberg-Wollheim; C Sindic; B Stubinski; B Uitdehaag; D Li Journal: Neurology Date: 2006-09-26 Impact factor: 9.910
Authors: Ludwig Kappos; Mark S Freedman; Chris H Polman; Gilles Edan; Hans-Peter Hartung; David H Miller; Xavier Montalbán; Frederik Barkhof; Ernst-Wilhelm Radü; Lars Bauer; Susanne Dahms; Vivian Lanius; Christoph Pohl; Rupert Sandbrink Journal: Lancet Date: 2007-08-04 Impact factor: 79.321
Authors: C Ford; A D Goodman; K Johnson; N Kachuck; J W Lindsey; R Lisak; C Luzzio; L Myers; H Panitch; J Preiningerova; A Pruitt; J Rose; H Rus; J Wolinsky Journal: Mult Scler Date: 2010-01-27 Impact factor: 6.312
Authors: Jonathan J Cho; Joshua M Stewart; Theodore T Drashansky; Maigan A Brusko; Ashley N Zuniga; Kyle J Lorentsen; Benjamin G Keselowsky; Dorina Avram Journal: Biomaterials Date: 2017-07-24 Impact factor: 12.479
Authors: Stuart D Cook; Suhayl Dhib-Jalbut; Peter Dowling; Luca Durelli; Corey Ford; Gavin Giovannoni; June Halper; Colleen Harris; Joseph Herbert; David Li; John A Lincoln; Robert Lisak; Fred D Lublin; Claudia F Lucchinetti; Wayne Moore; Robert T Naismith; Carlos Oehninger; Jack Simon; Maria Pia Sormani Journal: Int J MS Care Date: 2012
Authors: Andrew J Solomon; Dennis N Bourdette; Anne H Cross; Angela Applebee; Philip M Skidd; Diantha B Howard; Rebecca I Spain; Michelle H Cameron; Edward Kim; Michele K Mass; Vijayshree Yadav; Ruth H Whitham; Erin E Longbrake; Robert T Naismith; Gregory F Wu; Becky J Parks; Dean M Wingerchuk; Brian L Rabin; Michel Toledano; W Oliver Tobin; Orhun H Kantarci; Jonathan L Carter; B Mark Keegan; Brian G Weinshenker Journal: Neurology Date: 2016-08-31 Impact factor: 9.910