Use of individualized cutoffs for baseline cognitive function to predict disability progression in an integrated RRMS clinical trial database
Author(s): ,
M.P. Sormani
Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy
A. Pace
Biogen, Cambridge, MA, United States
C. Castrillo
Biogen, Cambridge, MA, United States
K. Raghupathi
Biogen, Cambridge, MA, United States
ECTRIMS Online Library. Sormani M.
Oct 9, 2015; 116356
Dr. Maria Pia Sormani
Dr. Maria Pia Sormani
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Abstract: P1506

Type: Poster LB

Abstract Category: Invited / Oral LB / Poster LB

Background: Baseline (BL) cognitive function has been identified as a predictor of clinical disability progression in an integrated Phase 3 relapsing-remitting multiple sclerosis clinical trial database. The ability to implement this finding in clinical practice at the individual patient level could lead to improved management and better outcomes.

Objectives: To develop individual patient level cutoffs for BL cognitive function that are predictive of disability progression.

Methods: Data from 4 placebo-controlled Phase 3 trials of 3 different disease-modifying therapies were integrated at the individual patient level, employing common variable and outcome definitions. Expected BL 3-Second Paced Auditory Serial Addition Test (PASAT-3) was calculated for each patient by a negative binomial model with number of incorrect items as the outcome, using BL demographic and clinical characteristics as covariates. Patients were categorized into two groups, those whose actual observed BL cognitive function was lower and higher than expected. Risk of time to 24-week confirmed clinical disability progression, using outcome definitions based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Visual Function Test (VFT), was compared for these two groups in placebo-treated patients.

Results: Complete data for BL PASAT-3 and model covariates were available for 3663 patients. The final model for expected PASAT-3 included age, BL EDSS, and BL T2 volume as covariates. 39% of patients were categorized in the lower than expected BL cognitive function group. In placebo-treated patients (n=1154), there was greater risk of disability progression for patients with lower than expected BL cognitive function as follows: EDSS progression (HR=1.41; 95% confidence interval (CI): 1.02, 1.96; p=0.04); EDSS, timed 25-foot walk, or 9-hole peg test progression (HR=1.39; 95% CI: 1.09, 1.78, p=0.009); and EDSS, MSFC, or VFT progression (HR=1.25; 95% CI: 0.99, 1.58; p=0.06).

Conclusions: This analysis demonstrates the potential for implementing the finding that BL cognitive function is predictive of disability progression into routine clinical practice at the individual patient level. Evaluation of cognitive function, which has been associated with premorbid cognitive reserve, MS-related structural brain tissue damage, and functional connectivity, in clinical practice may be beneficial in guiding assessment of individual patient prognosis.


Maria Pia Sormani received consulting fees from Biogen Merck Serono, Novartis, TEVA, Genzyme, Roche, Synthon

Amy Pace 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.

Kartik Raghupathi 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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