5th Joint triennial congress of the European and Americas Committees
for Treatment and Research in Multiple Sclerosis
Amsterdam, The Netherlands

19.10.2011 - 22.10.2011
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Home - 21.10.2011 - Immunomodulation 2

Immunomodulation 2

Friday, October 21, 2011, 15:30 - 17:00

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

D. Goodin, A. Reder, G. Ebers, G. Cutter, M. Kremenchutzky, J. Oger, D. Langdon, M. Rametta, K. Beckmann, V. Knappertz (San Francisco, Chicago, US; Oxford, GB; Birmingham, US; London, Vancouver, CA; Surrey, GB; Wayne, Montville, US)

Objective: Examine the predictive value of baseline and short-term (2 year) outcomes on all-cause 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 multiple sclerosis.
Methods: Patient vital status was determined. Baseline and on-study characteristics from the RCT were examined in unadjusted and adjusted Cox proportional hazard regression models as potential predictors of mortality. The joint influence of all baseline variables and treatment on survival was assessed using stepwise multivariate Cox regression.
Results: At a median of 21.1 years after RCT 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). In the unadjusted models, assignment to IFNB-1b 250 mcg and several baseline characteristics (Expanded Disability Status Scale [EDSS] score, T2 burden of disease), magnetic resonance imaging [MRI] third ventricle size) were predictive of mortality. Furthermore, 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. In the adjusted models, the HR for the treatment effect on mortality was stable and independent of the baseline variables’ effects. However, on-study MRI characteristics were consistently found not to be predictive of mortality, and the predictive value of other on-study clinical parameters varied. In the multivariate analysis the IFNB-1b 250 mcg treatment effect on mortality was maintained (HR=0.533). Similar results for all analyses were seen with IFNB-1b 50 mcg.
Conclusions: There was a significant survival advantage in this cohort of patients receiving early IFNB-1b treatment versus placebo. The treatment-related survival HR was essentially unchanged by the inclusion of baseline variables. On-study MRI measures were not predictive of mortality. As IFNB-1b is known to impact short-term trial outcomes and is itself associated with reduced mortality, some association between the 2-year on-study variables and mortality is anticipated.

This study was supported by Bayer HealthCare Pharmaceuticals, Montville, NJ, USA