title: Progression rates and sample size estimates for PPMS based on the CLIMB study population.
abstract: BACKGROUND
  The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts.
  
  
  OBJECTIVE
  The objective of this paper is to characterize demographic and clinical characteristics of PPMS and assess rate of disability progression.
  
  
  METHODS
  We studied PPMS (n = 73) and relapsing-onset MS (ROMS) patients (n = 1541) enrolled in CLIMB, a longitudinal study of MS patients at the Brigham and Women's Hospital (Boston, MA). Disability progression for each group was compared using interval-censored survival analysis and time to six-month sustained progression.
  
  
  RESULTS
  The PP group had a 1.09:1 male:female ratio compared to 1:2.89 for the RO group and greater mean age of onset (PP: 44.4±9.6; RO: 32.7±9.9; p < 0.0001). Motor symptoms at onset and first symptoms localized to spinal cord were each strongly associated with PPMS (p < 0.001). Median time from onset to EDSS 6.0 was faster in PPMS (p < 0.001). PPMS patients progressed faster to EDSS 3 (p < 0.001) and from EDSS 3 to 6 (p < 0.001). Median time to sustained progression in the PP group was 4.85 years (95% CI 2.83-8.35), significantly faster than the RO group (p < 0.001).
  
  
  CONCLUSIONS
  Our modern PPMS cohort is demographically similar to previously studied cohorts. PPMS is associated with faster disability accrual than ROMS. Current real-world observations of time to sustained progression will inform design of new clinical trials for PPMS.
authors: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, USA.
authors: Kesav
authors: K
authors: Raghavan
authors: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, USA/Biostatistics Center, Massachusetts General Hospital, USA.
authors: Brian C
authors: BC
authors: Healy
authors: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, USA.
authors: Robert L
authors: RL
authors: Carruthers
authors: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, USA tchitnis@partners.org.
authors: Tanuja
authors: T
authors: Chitnis
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic / Q000592:standards; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis*; D012107:Research Design / Q000592:standards*; D018401:Sample Size; D012720:Severity of Illness Index; D013997:Time Factors
keywords: Epidemiology; primary progressive multiple sclerosis