Progression rates and sample size estimates for PPMS based on the CLIMB study population

Mult Scler. 2015 Feb;21(2):180-8. doi: 10.1177/1352458514541976. Epub 2014 Jul 28.

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.

Keywords: Epidemiology; primary progressive multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Clinical Trials as Topic / standards
  • Disease Progression*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / diagnosis*
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis*
  • Research Design / standards*
  • Sample Size
  • Severity of Illness Index*
  • Time Factors