Definitions of primary-progressive multiple sclerosis trajectories by rate of clinical disability progression

Background: Patients with primary progressive multiple sclerosis (PPMS) vary in the rate of disability progression. Objective: To classify clinical disability trajectories by rate of disability progression and evaluate predictive variables in PPMS patients. Methods: We analyzed the cumulative incidence of progression to disability and in accordance defined clinical PPMS disability trajectories. Correlation was performed with age, gender and disability at first presentation. Estimated onset was calculated and validated by the mathematical slope of disability progression. Results: The cohort included 304 PPMS patients, 146 (48%) were females, the mean age at first visit was 41.1 years, and the median follow up was 18.9 years. Median time to reach moderate and severe disability was 4.5 years (95%CI 3.8–5.2) and 12.6 years (95%CI 10.1–14.2), respectively. Extremely fast patients (3.3%) progressed to severe disability within 2-years, while very slow patients (4.7%) did not progress to moderate disability even 20 years after first presentation. Age and gender were not associated with progression. Moderate disability at first visit was associated with faster progression to severe disability. Mean estimated range of disease onset was between 4.3 to 9.9 years prior to first presentation. Conclusions: Majority of PPMS patients progressed to moderate disability within 5-years and to severe disability within 15-years from first presentation. Clinical disability progression trajectories can help treatment-related decisions.