New Study Details The Various Ways Patients with Multiple Sclerosis Develop Impairment
A new study conducted by researchers from the Corrine Goldsmith Dickinson Center for Multiple Sclerosis at Icahn School of Medicine at Mount Sinai in collaboration with Novartis, the University of Oxford and and key MS experts across the globe, has revealed detailed information on the various ways patients with multiple sclerosis (MS) acquire disability. Analyzing both the role of relapses on long-term outcomes and the role of worsening that occurs independent of relapse activity, the study, published February 1 in Brain, also shows the benefit of treatment on longer term outcomes.
Patients with MS acquire disability 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 disability accumulation.
Utilizing the Novartis-Oxford MS data pool (NO.MS), spanning all MS phenotypes (pediatric MS, relapsing remitting MS [RRMS], secondary progressive MS [SPMS], primary progressive MS [PPMS]), the study team evaluated clinical and MRI data from more than 27,000 patients who had been followed for up to 15 years. They analyzed three datasets: (A) A full analysis dataset containing all observational and randomized controlled clinical trials in which disability relapses were assessed; (B) All phase 3 clinical trials; and (C) 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 MS, 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 < 0.001. Pre-existing disability and older age were the principal risk factors for incomplete relapse recovery. For placebo-treated patients with minimal disability (EDSS 1) it took 8.95 years until increased limitation in walking ability (EDSS 4) and 18.48 years to require walking assistance (EDSS 6). Treating patients with disease modifying therapies delayed these times significantly by 3.51 years (95% confidence limit: 3.19, 3.96) and by 3.09 years (2.60, 3.72), respectively. In RRMS, patients who worsened exclusively due to RAW events took a similar time to reach milestone EDSS values 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. “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 multiple sclerosis.”
Fred Lublin, MD, Saunders Family Professor of Neurology, Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at the Icahn School of Medicine at Mount Sinai.
This study was supported by Novartis Pharma AG. Novartis employees contributed to study design, analysis of the data, and the decision to publish the results.
How patients with multiple sclerosis acquire disability. Brain, February 1, 2022.
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The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.