LONDON—A dynamic model based on long-term observations and a statistical modeling approach can help neurologists predict the future disability trajectory of a new patient with primary progressive multiple sclerosis (MS), according to a study presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). The existence of heterogeneous classes of patients should be considered in the design of future clinical trials in primary progressive MS that have time-to-reach-disability milestones as their primary end points, said the researchers.
Several natural history studies of patients with primary progressive MS have been reported from international registries over the past decades. This population had a consistently heterogeneous rate of disability accumulation. Time to reach the milestone of an Expanded Disability Status Scale (EDSS) score of 6 ranged between seven and 14 years from disease onset.
Alessio Signori, PhD, postdoctoral researcher in biostatistics at the University of Genoa, Italy, and colleagues sought to identify subgroups of patients with primary progressive MS who had similar longitudinal EDSS trajectories over time. The investigators included in their analysis all patients with primary progressive MS in the MSBase international registry who had their first EDSS assessment within five years of disease onset. Longitudinal EDSS scores were modeled by a latent class mixed model (LCMM) using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups (ie, latent classes) that have similar characteristics.
Alessio Signori, PhD
A total of 853 participants with primary progressive MS (51.7% female) from 24 countries with a mean age at onset of 42.4, a median baseline EDSS of 4, and 2.4 years of disease duration were included. LCMM detected three distinct subgroups of patients with a mild (n = 143; 16.8%), a moderate (n = 378; 44.3%), and a severe (n = 332; 38.9%) disability trajectory, respectively. Time from disease onset to diagnosis was shortest for the severe group. Median time to an EDSS of 4 was 14, five, and 3.7 years for the three groups, respectively. The probability of reaching an EDSS of 6 at 10 years was 0%, 46.5%, and 83.1%, respectively. Increasing severity of the disability time course was related to a decreasing frequency of patients with at least one relapse during follow-up (ie, from 47.6% to 36.5%).
“Using this modeling approach, it is possible to predict the future disease course of a subject with primary progressive MS using early EDSS assessments,” said Dr. Signori. “By using only one year of EDSS monitoring, 73% of patients are correctly classified in their disability trajectory group (mild, moderate, or severe). After three years, this proportion is 87%, and after five years, it is 92%.”