Defining secondary progressive multiple sclerosis

Abstract

A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis.

Silent progression in disease activity–free relapsing multiple sclerosis

“…34 The EDSS is nonlinear, and patients with scores <3 are less likely to show more year-to-year changes than those with scores between 3 and 6. Thus, insidious progression accrues in many early RRMS patients who remain classified as having relapsing MS.…”

Is Time to Reach EDSS 6.0 Faster in Patients with Late-Onset versus Young-Onset Multiple Sclerosis?

“…Among the patients with ≥ 5 years follow-up after the SPMS diagnosis, 78% showed a positive disability trajectory and 70% reached an EDSS of ≥ 6 at censoring. [24] Others tried to measure the disease progression index using the EDSS score as a numerator and disease duration as a denominator. [7, 25] Kis and colleagues pair-matched 52 LOMS with 52 YOMS patients on gender and disease duration and reported a higher disease progression index in LOMS cohort (0.60 vs.…”

NeurEx: digitalized neurological examination offers a novel high‐resolution disability scale

“…Its drawback is the discrete nature with only 19 possible “levels” of progression, leading to a median annualized EDSS change measured in large natural history cohorts of 0.1 13. This rate of progression is unmeasurable by EDSS in intervals shorter than 5‐10 years, as the minimal measurable EDSS step is 0.5.…”