Contributions
Abstract: P1017
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Clinical assessment tools
Introduction: Expanded disability status scale (EDSS) progression has been the widely accepted and utilized metric within the MS community to best assess the effect of treatments on disability accumulation in MS phase III clinical trials. Recent trials reported an unexpectedly low rate of EDSS progression events and, a recent meta-analysis showed that EDSS progression rates in placebo arms of clinical trials declined over time.
Objectives: We investigated whether the geographical region in the world where a clinical trial was conducted may potentially influence the rate of reported progression events compared with those in differing geographical regions.
Methods: A post-hoc analysis of 3 pooled randomized RRMS clinical trials (ALLEGRO, BRAVO and CONCERTO) with the same inclusion criteria was used to analyze two clinical outcomes: 1) the disability progression (1.0 point increase in EDSS score if baseline score was between 0 and 5.0; or 0.5 point increase if baseline score was 5.5 or greater, sustained for 3 months; 2) the Timed 25-Foot Walk (T25FW) progression score, defined as an increase of at least 20% from baseline, sustained for 3 months. EDSS and T25FW progression rates were evaluated according to the geographical region where patients were enrolled by a multivariate Cox model.
Results: 1746 placebo patients were included in the analysis: 291 (17%) in Europe, 145 (8%) in USA/Canada and 1310 (75%) in East Europe. At univariate analysis, the EDSS progression risk was significantly heterogeneous (p< 0.0001) among the 3 geographical regions: a greater 2-year risk was observed in USA/Canada (21.4%), followed by Europe (13.1%), and the lowest risk was in East Europe (10.8%). The results were unchanged when correcting for unbalances of baseline variables. Conversely, there was no significant difference in T25FWT progression among patients enrolled in different countries (East Europe=16.9%, Europe=13.4%, USA/Canada=13.9%).
Conclusions: These results suggest that differing rates of EDSS progression events detected in different geographical regions of the world may be strongly influenced by heterogeneity in methodology and criteria used for EDSS progression assessment. At a time when disease progression and disability represent the key targets for future interventions in MS, establishment of more quantitative and objective outcome measures remain a key priority for researchers in the field.
Disclosure: This study received no funds. TEVA allowed to re-analyze 3 clinical trial datasets.
FB and AS received teaching honoraria from Novartis.
LC and IM: nothing to disclose
TL and APT are TEVA employees.
JRS was a TEVA employer at the time of data analysis.
MPS has received personal compensation for consulting services and for speaking activities from Merck, Teva, Novartis, Roche, Sanofi Genzyme, Medday, GeNeuro and Biogen.
Abstract: P1017
Type: Poster Sessions
Abstract Category: Clinical aspects of MS - Clinical assessment tools
Introduction: Expanded disability status scale (EDSS) progression has been the widely accepted and utilized metric within the MS community to best assess the effect of treatments on disability accumulation in MS phase III clinical trials. Recent trials reported an unexpectedly low rate of EDSS progression events and, a recent meta-analysis showed that EDSS progression rates in placebo arms of clinical trials declined over time.
Objectives: We investigated whether the geographical region in the world where a clinical trial was conducted may potentially influence the rate of reported progression events compared with those in differing geographical regions.
Methods: A post-hoc analysis of 3 pooled randomized RRMS clinical trials (ALLEGRO, BRAVO and CONCERTO) with the same inclusion criteria was used to analyze two clinical outcomes: 1) the disability progression (1.0 point increase in EDSS score if baseline score was between 0 and 5.0; or 0.5 point increase if baseline score was 5.5 or greater, sustained for 3 months; 2) the Timed 25-Foot Walk (T25FW) progression score, defined as an increase of at least 20% from baseline, sustained for 3 months. EDSS and T25FW progression rates were evaluated according to the geographical region where patients were enrolled by a multivariate Cox model.
Results: 1746 placebo patients were included in the analysis: 291 (17%) in Europe, 145 (8%) in USA/Canada and 1310 (75%) in East Europe. At univariate analysis, the EDSS progression risk was significantly heterogeneous (p< 0.0001) among the 3 geographical regions: a greater 2-year risk was observed in USA/Canada (21.4%), followed by Europe (13.1%), and the lowest risk was in East Europe (10.8%). The results were unchanged when correcting for unbalances of baseline variables. Conversely, there was no significant difference in T25FWT progression among patients enrolled in different countries (East Europe=16.9%, Europe=13.4%, USA/Canada=13.9%).
Conclusions: These results suggest that differing rates of EDSS progression events detected in different geographical regions of the world may be strongly influenced by heterogeneity in methodology and criteria used for EDSS progression assessment. At a time when disease progression and disability represent the key targets for future interventions in MS, establishment of more quantitative and objective outcome measures remain a key priority for researchers in the field.
Disclosure: This study received no funds. TEVA allowed to re-analyze 3 clinical trial datasets.
FB and AS received teaching honoraria from Novartis.
LC and IM: nothing to disclose
TL and APT are TEVA employees.
JRS was a TEVA employer at the time of data analysis.
MPS has received personal compensation for consulting services and for speaking activities from Merck, Teva, Novartis, Roche, Sanofi Genzyme, Medday, GeNeuro and Biogen.