Saturday, 18 February 2012

ECTRIMS 2011: IFNbeta and 21-yr survival

Goodin et al.  Predictive value of baseline and short-term outcomes on mortality in multiple sclerosis: data from the Interferon Beta-1b 21-Year Long-Term Follow-Up Study.

Objective: This study examined the predictive value of baseline and short-term (2 year) outcomes on mortality in the 21-Year Long-Term Follow-Up (21Y-LTF) study, which investigated the fate of patients 21 years after the start of the randomized controlled trial (RCT) of interferon beta-1b (IFNB-1b; Betaferon^®) in MS. 


Results
  1. 21 years after enrolment, 98.4% (366/372) of patients were identified and 81 deaths recorded (21.8%). As reported previously, those originally randomized to IFNB-1b 250 mcg had a significant reduction in all-cause mortality over LTF compared with placebo (hazard ratio [HR]=0.532, P=0.0173). 
  2. Assignment to IFNB-1b 250 mcg and several baseline characteristics (EDSS score, T2 burden of disease), third ventricle size on MRI (a marker of atrophy or shrinkage of the brain) were predictive of mortality. 
  3. On-study characteristics (EDSS progression from baseline to year 2, annualized relapse rate over 2 years, MRI T2 activity at Year 2) were also predictive of mortality. 
  4. The hazard ratio (HR) for the treatment effect on mortality was stable and independent of the baseline variables’ effects. 
  5. On-study MRI characteristics were consistently found not to be predictive of mortality, and the predictive value of other on-study clinical parameters varied. 
  6. When taking all factors into account the IFNB-1b 250 mcg treatment effect on mortality was maintained (HR=0.533). 
  7. Similar results for all analyses were seen with IFNB-1b 50 mcg or low dose IFNB-1b. 
Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFNB-1b treatment versus placebo. The treatment-related increase in survival was unchanged by the inclusion of baseline variables.




"This abstract is quite complex and you may find it difficult to interpret. The bottom line is that starting treatment with interferon beta 3-years earlier, compared to MS'ers in the placebo-arm, increased their chance of being alive at 21 years by ~50%. In addition, the number of relapses in the 2-years on the trial also predicted mortality; another reason to reduce relapses early on in the course of MS and necessarily within the first 2-years."

7 comments:

  1. Prof G,

    Very difficult to interpet. But the fact that the study looked at mortality rates emphasises that this disease kills - eirher quickly or slowly.

    ReplyDelete
  2. "Life is a sexually transmitted disease with 100% mortality."

    C'est la vie!

    Wasn't there a theory about MS being a sexually transmitted disease?

    ReplyDelete
  3. So out of 81 deaths, 81/3 where on the Betaferon group and the rest on the placebo group?

    More proper would be to have the same analysis for all years, from the first to the 21st, in order to see the fluctuations.

    But, in the end, many things could have been different in the lives of the patients apart from taking Betaferon late or early:
    1. What were the treatments they received after their participation in the trial?
    2. Were they engaged in any accidents?
    3. What was their standard of living?
    4. What was the their family status?
    5. How supportive was their environment in physical and emotional terms?
    6. What other medical conditions were encountered?

    The list could go on. The point is, why were these factors excluded?

    ReplyDelete
  4. Re: "The list could go on. The point is, why were these factors excluded?"

    The list does not need to go on. The vast majority of the deaths were MS-related, in other words these people died because of their MS. Imagine if they had started IFNbeta 3 years earlier the majority of them would still be alive.

    Regarding other confounding factors; these were dealt with in the randomisation process, which is why we do randomised studies. I can't recall any imbalances that were highlighted in the presentation. If I recall correctly the statistical analysis dealt with all factors and the only thing that explained the increased survival in the IFNbeta group was earlier treatment.

    Not to worry the paper is due out in late April; you can read it in full then.

    ReplyDelete
  5. Re "The vast majority of the deaths were MS-related"

    Aren't there any factors that could deteriorate ones MS, ie smoking, high fat diet?

    In any case, it is difficult to believe that apart from the time of treatment and MS severity, everything else was the same for 21 years.

    "...several baseline characteristics (EDSS score, T2 burden of disease), third ventricle size on MRI (a marker of atrophy or shrinkage of the brain) were predictive of mortality. "

    Could this mean that the placebo group was destined to have worse outcome right from the beginning? Maybe the initial randomisation process was not so random after all?

    ReplyDelete
  6. It would be good to see this duplicated. A more death-prone group may have randomly ended up in the placebo group. This is worth more investigation, these are remarkably good effects on mortality for the interferon group.

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.