Abstract: Consequences Of Different Definitions Of Confirmed Disability Progression (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Saturday, June 1, 2013

Ron Hashmonay, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ

Niklas Bergvall, PhD , Novartis Pharma AG, Basel, Switzerland

Nikolaos Sfikas, PhD , Novartis Pharma AG, Basel, Switzerland

Peter Chin, MD , Novartis Pharmaceuticals Corporation, East Hanover, NJ

Philipp von Rosenstiel, MD , Novartis Pharma AG, Basel, Switzerland

Background: In a previous indirect comparison of 3-month confirmed disability progression using data from the FREEDOMS and AFFIRM trials, the importance of adjusting for differences in patient populations and in definitions of endpoints across trials has been demonstrated.

Objectives: To assess the impact of differences in definitions of 3- and 6-month confirmed disability progression used across randomized clinical trials of MS therapies

Methods: The definition of 3- and 6-month confirmed disability progression used in the AFFIRM trial was used to perform post hoc analyses in the intent-to-treat population in the FREEDOMS trial. In the AFFIRM trial, the definitions for patients with a baseline Expanded Disability Status Scale (EDSS) score of 0 were an increase from baseline of ≥1.5 that was sustained for 12 and 24 weeks, respectively, for 3- and 6-month confirmed disability progression. In the FREEDOMS trial, the corresponding definition was an increase in EDSS of ≥1. The Cox proportional hazards model was used to model time to event adjusted for treatment, country, baseline EDSS, and age as defined in the study protocol. Hazard ratios (HRs), 95% CIs, and Pvalues for the Cox proportional hazard model were provided.

Results: Using the original definition of confirmed disease progression in the FREEDOMS trial, the risk reduction in 3-month disability progression over 2 years was 30% (HR, 0.70) for the treatment group relative to the placebo group (P=0.024). Using the AFFIRM definition of confirmed disease progression, the corresponding reduction was 36% (HR, 0.64). In the analyses of 6-month confirmed disability, the corresponding reductions were 37% (HR, 0.63) and 43% (HR, 0.57) relative to the placebo group. Similar trends in changes of point estimates were observed for the 3- and 6-month confirmed disability progressions in the FREEDOMS II trial.

Conclusions: In addition to the importance of adjusting for differences in patient characteristics in indirect comparisons, these results show that differences in definition of confirmed disease progression may have a relevant impact when comparing point estimates of 3- and 6-month confirmed disease progression across trials.

P13 Consequences Of Different Definitions Of Confirmed Disability Progression