Assessing disability progression with the Multiple Sclerosis Functional Composite.
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 >or=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.


CONCLUSIONS
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.
Rudick
R A
RA
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH 44106, USA. rudickr@ccf.org
Polman
C H
CH
Cohen
J A
JA
Walton
M K
MK
Miller
A E
AE
Confavreux
C
C
Lublin
F D
FD
Hutchinson
M
M
O'Connor
P W
PW
Schwid
S R
SR
Balcer
L J
LJ
Lynn
F
F
Panzara
M A
MA
Sandrock
A W
AW
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D003071:Cognition; D004185:Disability Evaluation; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D000069442:Natalizumab; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome; D034941:Upper Extremity / Q000503:physiopathology; D016138:Walking
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta; D000068556:Interferon beta-1a