Assessing disability progression with the Multiple Sclerosis Functional Composite

• Published in: Multiple sclerosis Vol. 15; no. 8; pp. 984 - 997
• Main Authors: Rudick, RA, Polman, CH, Cohen, JA, Walton, MK, Miller, AE, Confavreux, C, Lublin, FD, Hutchinson, M, O’Connor, PW, Schwid, SR, Balcer, LJ, Lynn, F, Panzara, MA, Sandrock, AW
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-08-2009; Sage Publications; Sage Publications Ltd
• Subjects: Adult; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Cognition; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disability Evaluation; Disease Progression; Drug Therapy, Combination; Female; Health Status Indicators; Humans; Immunologic Factors - therapeutic use; Interferon beta-1a; Interferon-beta - therapeutic use; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - physiopathology; Multiple Sclerosis, Relapsing-Remitting - psychology; Natalizumab; Neurology; Predictive Value of Tests; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recurrence; Sensitivity and Specificity; Time Factors; Treatment Outcome; Upper Extremity - physiopathology; Walking; Multiple Sclerosis Functional Composite; clinical end points; disability progression; relapsing-remitting; multiple sclerosis; natalizumab; Disability; Nervous system diseases; Multiple sclerosis; Natalizumab; Central nervous system disease; Degenerative disease; Inflammatory disease
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458509106212

Background
The initial Multiple Sclerosis Functional Composite (MSFC) proposal was a three-part composite of quantitative measures of ambulation, upper extremity function, and cognitive function expressed as a single composite Z-score. However, the clinical meaning of an MSFC Z-score change is not obvious. This study instead used MSFC component data to define a patient-specific disease progression event.
Objective
Evaluate a new method for analyzing disability progression using the MSFC.
Methods
MSFC progression was defined as worsening from baseline on scores of at least one MSFC component by 20% (MSFC Progression-20) or 15% (MSFC Progression-15), sustained for ≥3 months. Progression rates were determined using data from natalizumab clinical studies (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]). Correlations between MSFC progression and other clinical measures were determined, as was sensitivity to treatment effects.
Results
Substantial numbers of patients met MSFC progression criteria, with MSFC Progression-15 being more sensitive than MSFC Progression-20, at both 1 and 2 years. MSFC Progression-20 and MSFC Progression-15 were related significantly to Expanded Disability Status Scale (EDSS) score change, relapse rate, and the SF-36 Physical Component Summary (PCS) score change. MSFC Progression-20 and MSFC Progression-15 at 1 year were predictive of EDSS progression at 2 years. Both MSFC progression end points demonstrated treatment effects in AFFIRM, and results were replicated in SENTINEL.
Conclusion
MSFC Progression-20 and MSFC Progression-15 are sensitive measures of disability progression; correlate with EDSS, relapse rates, and SF-36 PCS; and are capable of demonstrating therapeutic effects in randomized, controlled clinical studies.