A new study has revealed detailed information on the various ways patients with multiple sclerosis (MS) become disabled, analyzing both the role of relapses on long-term outcomes and the role of worsening that occurs independent of any relapse activity. The study, led by researchers from The Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Icahn School of Medicine at Mount Sinai and collaborators at Novartis and the University of Oxford and published February 1 in Brain, also shows the benefit of treatment on longer-term outcomes.

Patients with multiple sclerosis become disabled either through relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins, and the extent to which MS therapies delay the onset or worsening of disability.

Using the Novartis-Oxford MSdata pool, spanning all multiple sclerosis phenotypes and pediatric multiple sclerosis, the study team evaluated clinical and MRI data from more than 27,000 patients who had been followed for 15 years or more. They analyzed three datasets: A full analysis dataset containing all observational and randomized controlled clinical trials in which disability relapses were assessed, all phase 3 clinical trials and all placebo-controlled phase 3 clinical trials. They determined the relative importance of RAW and PIRA, investigated the role of relapses on all-cause disability worsening, and observed the impact of the mechanism of worsening and disease-modifying therapies on the time to reach milestone disability levels.

The research analysis revealed that PIRA started early in multiple sclerosis, occurred in all phenotypes and became the principal driver of disability accumulation in the progressive phase of the disease. Relapses significantly increased the hazard of all-cause disability worsening events: Following a year in which relapses occurred (vs. a year without relapses), the hazard increased by 31–48%; all p

"Our data confirm relapses contribute to the accumulation of disability, primarily early in multiple sclerosis, and that progression independent of relapse activity can start early in relapsing, remitting MS and becomes the dominant driver of disability accumulation as the disease evolves," said Fred Lublin, MD, lead author of the study and Saunders Family Professor of Neurology and Director of The Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Icahn Mount Sinai. "Pre-existing disability and older age are the principal risk factors for further disability accumulation. Importantly, using disease-modifying therapies delays disability accrual by years, with the potential to gain time being the hightest in the early stage of muiltple sclerosis."