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

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

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Partners Multiple Sclerosis Center, Brigham and Women's Hospital, USA.
Partners Multiple Sclerosis Center, Brigham and Women's Hospital, USA/Biostatistics Center, Massachusetts General Hospital, USA.
Partners Multiple Sclerosis Center, Brigham and Women's Hospital, USA



The clinical trial design for primary progressive multiple sclerosis (PPMS) requires understanding of disability progression in modern patient cohorts.


The objective of this paper is to characterize demographic and clinical characteristics of PPMS and assess rate of disability progression.


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.


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).


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.


Epidemiology; primary progressive multiple sclerosis

[Indexed for MEDLINE]

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