title: Assessing disability progression with the Multiple Sclerosis Functional Composite.
abstract: 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.
authors: Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH 44106, USA. rudickr@ccf.org
authors: R A
authors: RA
authors: Rudick
authors: C H
authors: CH
authors: Polman
authors: J A
authors: JA
authors: Cohen
authors: M K
authors: MK
authors: Walton
authors: A E
authors: AE
authors: Miller
authors: C
authors: C
authors: Confavreux
authors: F D
authors: FD
authors: Lublin
authors: M
authors: M
authors: Hutchinson
authors: P W
authors: PW
authors: O'Connor
authors: S R
authors: SR
authors: Schwid
authors: L J
authors: LJ
authors: Balcer
authors: F
authors: F
authors: Lynn
authors: M A
authors: MA
authors: Panzara
authors: A W
authors: AW
authors: Sandrock
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta; D000068556:Interferon beta-1a