Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis

With the aid of a Bayesian statistical model of the natural course of relap sing remitting Multiple Sclerosis (MS), we identify short-term clinical pre dictors of long-term evolution of the disease, with particular focus on pre dicting onset of secondary progressive course (failure event) on the basis of patient information available at an early stage of disease. The model sp ecifies the full joint probability distribution for a set of variables incl uding early indicator variables (observed during the early stage of disease ), intermediate indicator variables (observed throughout the course of dise ase, prefailure) and the time to failure. Our model treats the intermediate indicators as a surrogate response event, so that in right-censored patien ts, these indicators provide supplementary information pointing towards the unobserved failure times. Moreover, the full probability modelling approac h allows the considerable uncertainty which affects certain early indicator s, such as the early relapse rates, to be incorporated in the analysis. Wit h such a model, the ability of early indicators to predict failure can be a ssessed more accurately and reliably, and explained in terms of the relatio nship between early and intermediate indicators. Moreover, a model with the aforementioned features allows us to characterize the pattern of disease c ourse in high-risk patients, and to identify short-term manifestations whic h are strongly related to long-term evolution of disease, as potential surr ogate responses in clinical trials. Our analysis is based on longitudinal d ata from 186 MS patients with a relapsing-remitting initial course. The fol lowing important early predictors of the time to progression emerged: age; number of neurological functional systems (FSs) involved; sphincter, or mot or, or motor-sensory symptoms; presence of sequelae after onset. During the first 3 years of follow up, to reach EDSS greater than or equal to 4 outsi de relapse, to have sphincter or motor relapses and to reach moderate pyram idal involvement were also found to be unfavourable prognostic factors. (C) 2001 Elsevier Science B.V. All rights reserved.