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Baseline cognitive function predicts clinical disability progression in an integrated RRMS clinical trial database
Author(s): ,
K. Raghupathi
Affiliations:
Biogen, Cambridge, MA, United States
,
A. Pace
Affiliations:
Biogen, Cambridge, MA, United States
,
G. Giovannoni
Affiliations:
Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, United Kingdom
,
B. Weinstock-Guttman
Affiliations:
Jacobs Neurological Institute, Buffalo, NY, United States
,
X. Montalban
Affiliations:
Vall d'Hebron University Hospital, Barcelona, Spain
,
R. Rudick
Affiliations:
Biogen, Cambridge, MA, United States
,
R. Hyde
Affiliations:
Biogen, Cambridge, MA, United States
,
C. Castrillo
Affiliations:
Biogen, Cambridge, MA, United States
,
J. Xiao
Affiliations:
Biogen, Cambridge, MA, United States
F. Pellegrini
Affiliations:
Biogen, Cambridge, MA, United States
ECTRIMS Online Library. Raghupathi K.
Oct 8, 2015; 115512
Kartik Raghupathi
Kartik Raghupathi
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Abstract: P317

Type: Poster

Abstract Category: Clinical assessment tools

Background: The ability to identify predictive factors for clinical disability progression in relapsing-remitting multiple sclerosis (RRMS) patients would enable better risk stratification, allowing more tailored treatment decisions, that can potentially lead to better individual outcomes. This is particularly important, given the availability of more than ten disease-modifying treatment (DMT) choices for RRMS and their associated benefits and risks.

Objectives: To utilize an integrated database of Phase 3 RRMS clinical trials as a platform to investigate baseline factors that predict clinically meaningful disability progression in placebo-treated patients.

Methods: Individual patient level clinical trial data from four Phase 3 trials of 3 different DMTs were integrated, employing common variable and outcome definitions. Missing baseline data were imputed employing Markov Chain Monte Carlo imputation. Complementary cross-validated Cox modelling approaches, including regression trees and the Least Absolute Shrinkage and Selection Operator (LASSO) method, were utilized to investigate baseline factors prognostic of time to various composite clinical disability progression outcomes, based on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and/or Visual Function Test (VFT), in placebo-treated patients. Findings were assessed for consistency across the statistical approaches and the various composite disability outcome definitions.

Results: Based on 1582 placebo-treated patients followed up to two years, 3-Second Paced Auditory Serial Addition Test (PASAT-3) was consistently identified as a baseline predictor across clinical disability progression outcomes, including outcomes not involving PASAT-3, using both statistical approaches. The physical component summary (PCS) score of the 36-Item Short-Form Health Survey (SF-36) was also consistently identified as having predictive value.

Conclusions: Baseline cognitive function - which has been associated with premorbid cognitive reserve, MS-related structural brain tissue damage, and functional connectivity - as well as patient self-reported assessment of physical health status are predictive of clinical disability progression in RRMS patients. Incorporating evaluation of cognitive function and patient-reported assessment of physical health into routine clinical care may be beneficial in guiding assessment of individual patient prognosis and management and care decisions.

Disclosure:

Kartik Raghupathi is a full-time employee of Biogen and holds stock in Biogen.

Amy Pace is a full-time employee of Biogen and holds stock in Biogen.

Gavin Giovannoni receives consulting fees for serving on scientific advisory board: AbbVie, Biogen, Canbex, Genzyme Sanofi, Ironwood, Novartis, Merck, Merck Serono, Roche, Synthon, Teva, Vertex; speaker honoraria: Abbvie, Biogen, Bayer Schering Pharma, Genzyme, Merck Serono, Teva, Sanofi; co-editor-in-chief Multiple Sclerosis and Related Disorders, Elsevier; research support unrelated to study from Biogen, Merck Serono, Novartis, Genzyme, Ironwood.

Bianca Weinstock-Guttman has participated in speaker´s bureaus and served as a consultant for Biogen, Teva Neuroscience, EMD Serono, Novartis, Genzyme & Sanofi, Acorda Therapeutics, Inc. and Genentech. Dr. Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence as well as Questcor Pharmaceuticals, Inc., and Shire. She serves in the editorial board for BMJ Neurology, Journal of International MS and CNS Drugs.

Xavier Montalban receives speaking honoraria and travel expense reimbursement for participation in scientific meetings, has been a steering committee member of clinical trials, or participated in advisory boards of clinical trials in the past years with: Actelion, Almirall, Bayer, Biogen, Genzyme, Merck, Neurotec, Novartis, Octapharma, Receptos, Roche, Sanofi, Teva and Trophos.

Rick Rudick is a full-time employee of Biogen and holds stock in Biogen.

Robert Hyde is a full-time employee of Biogen and holds stock in Biogen.

Carmen Castrillo is a full-time employee of Biogen and holds stock in Biogen.

James Xiao is a full-time employee of Biogen and holds stock in Biogen.

Fabio Pellegrini is a full-time employee of Biogen and holds stock in Biogen.

This study was funded by Biogen (Cambridge, MA, USA).

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