Goodin DS, Reder AT, Ebers GC, Cutter G, Kremenchutzky M, Oger J, Langdon D, Rametta M, Beckmann K, Desimone TM, Knappertz V. Survival in MS: A randomized cohort study 21 years after the start of the pivotal IFNβ-1b trial.Neurology. 2012 Apr 11. [Epub ahead of print]
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.
This study shows that there is advantage in early treatment with a DMT, as it appears to slow the generation of accumulation of disability that leads to death. This indicates that stopping relapses is a good thing and importantly indicates that we can treat early and aggressively with newer more effective DMT, then the future outcome for MSers will be even brighter and longer.
CoI: None
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.
This study shows that there is advantage in early treatment with a DMT, as it appears to slow the generation of accumulation of disability that leads to death. This indicates that stopping relapses is a good thing and importantly indicates that we can treat early and aggressively with newer more effective DMT, then the future outcome for MSers will be even brighter and longer.
CoI: None
Once again, great news if one has RRMS and a PCT willing to fund early and aggressive DMT treatments.
ReplyDeleteDo you guys ever think about how the majority of us progressive MSers may feel when we read stuff like this? How hopeless or situation suddenly becomes?
It's not fair!
Sorry, we are trying to interpret good and unfortunately bad news.
ReplyDeleteProf Ebers is one of the authors here.
ReplyDeleteDon't these conclusions contradict what he said in his guest post? Or did I misunderstand the quest post?
"Do you guys ever think about how the majority of us progressive MSers may feel when we read stuff like this? How hopeless or situation suddenly becomes?"
ReplyDeleteWe know exactly how you feel, which is why our primary research focus is on treatments for progressive MS.
Prof Ebers post was on outcomes and he said that he felt that relapses did not impact on long term outcomes
ReplyDeletehttp://multiple-sclerosis-research.blogspot.co.uk/2012/03/guest-post-prof-george-ebers.html
However I have heard him speak before where he suggested that the interferons did little in the long term and so you would be right to see a contradiction then.
Maybe he has looked at his data again and chnged his mind a little bit. He often comes up with new finding by examining the data again, eg. MS is increasing in women
Re: "Prof Ebers post was on outcomes and he said that he felt that relapses did not impact on long term outcomes."
ReplyDeleteThis suggests that interferon may be having other effects apart from reducing relapses. It is an anti-viral agent so it could be suppressing viruses.