Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network

Abstract

BackgroundOver the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.MethodsAll patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3–4.ResultsA total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria.ConclusionsContrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.

Deciphering multiple sclerosis disability with deep learning attention maps on clinical MRI

“…Furthermore, having at hand an excellent tool to discriminate patients according to their disability level may be extremely useful in contexts where the EDSS score is not obtained as part of routine practice ( Bove et al, 2023 ). Such a discriminating tool may allow the fast identification of patients who already present a certain degree of disability and who, therefore, are at high risk of reaching unfavourable clinical outcomes ( Signori et al, 2023 ). To further assess our model robustness to the actual disability threshold used to classify patients or the distribution of disability scores in the given study population, we carried out a post-hoc analysis on the in-house cohort where we only considered those patients with an EDSS ≤ 2.0 or ≥ 4.0 .…”

Long-term trajectories of ambulatory impairment in multiple sclerosis

“…This work adds to the modest literature that has characterized trajectories in MS for depression, Expanded Disability Status Scale, and healthrelated quality of life. 13,[31][32][33][34][35] An important future step would be to examine the relationships across these trajectories, as well as the directionality of these possible relationships. This study is also the largest study population, to our knowledge, in whom trajectories have been modeled.…”

Measuring disability in multiple sclerosis: the WHODAS 2.0

“…Modelling using various registries has described mild, moderate, and severe disability trajectories in both PPMS and SPMS [ 31 , 32 ]. A Swedish study examined trajectories of mean Sickness Absence and Disability Pension days per year (SA/DP) and found higher levels of SA/DP among pwMS of working age compared to the reference population [ 33 ].…”