Progression Rates and Sample Size Estimates for Primary Progressive Multiple Sclerosis 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: To characterize demographic and clinical characteristics of the CLIMB study (Boston, MA) PPMS patient cohort 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 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.