Relapses in Multiple Sclerosis Significantly Increased Likelihood of Disability Worsening

A new study published in Brain has revealed detailed information on how individuals with multiple sclerosis (MS) acquire disability. 

In retrospective analysis of observational and randomized controlled clinical trials that included over 27,000 individuals with MS, progression independent of relapse activity (PIRA) started early in MS. This was the case for all phenotypes, including pediatric MS, relapsing remitting MS [RRMS], secondary progressive MS [SPMS], and primary progressive MS [PPMS]). PIRA became the principal driver of disability accumulation in the progressive phase of MS. Relapses significantly increased the hazard of all-cause disability worsening events. In the year after a relapse compared to a year without relapse, the hazard ratio for progression increased by 31% to 48% (P<.001). 

For participants treated with placebo who had minimal disability (Expanded Disability Status Score [EDSS] 1), progression to EDSS 4 (limited ambulation) took 8.95 years and progression to EDSS 6 (need for assistive walking device) took 18.48 years. In those treated with disease modifying therapies (DMTs), the time to EDSS 4 was delayed by 3.51 years (95% CI: 3.19, 3.96) and EDSS 6 by 3.09 years (95% CI: 2.60, 3.72). Among those with RRMS, individuals who worsened exclusively due to relapse-associated worsening (RAW) events had similar times to reach EDSS milestones compared with those with PIRA events; the fastest transitions were observed in patients with PIRA and superimposed relapses.

“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 the Icahn School of Medicine at Mount Sinai. “Preexisting 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 highest in the early stage of multiple sclerosis.”