Multiple Sclerosis Progression May Not be Biphasic or Have Uniform Trajectory
VANCOUVER, BC—Patients with relapse-onset multiple sclerosis (MS) who have reached disease steps 3, 4, or 6 should still receive highly effective immunomodulatory therapy to mitigate disability accrual, according to authors of a research poster presentation at the 68th AAN Annual Meeting.
“Disease progression in moderately advanced and advanced MS is highly variable and amnesic to prior disease activity,” wrote Tomas Kalincik, MD, PhD, of the Department of Neurology, Royal Melbourne Hospital, in Melbourne, Australia, and coauthors. “However, increased utilization of higher efficacy therapy and lower annualized relapse rate during advanced MS are associated with a lower likelihood of accumulating significant disability.”
That finding ran contrary to previous studies which have suggested the progression of disability in MS is a biphasic process with a uniform trajectory in advanced disease, the coauthors noted.
To assess disability variability and predictability, and how the accumulation of disabilities is affected by immunomodulatory therapy, the research team extracted Expanded Disability Status Scale (EDSS) and clinical data, and treatment histories, for 32,336 patients from the multinational MSBase longitudinal cohort.
Patients whose data were included in the study had rapid-onset, clinically-definite MS or clinically isolated syndrome (CIS). Study outcomes included “variability of disability trajectories before and after the baseline EDSS steps (3, 4, or 6),” and clinical and demographic characteristics' associations. Study outcomes also included time from baseline to the outcome EDSS steps confirmed over three or more months. Disease-modifying therapies that were categorized as lower-efficacy included interferon beta preparations, glatiramer acetate, and teriflunomide. Higher-efficacy therapy included natalizumab, fingolimod, alemtuzumab, dimethyl fumarate, cladribine, rituximab, and mitoxantrone.
“Higher annualized relapse rate and lower persistence on higher-efficacy therapy during each epoch increased the hazard of reaching the outcome EDSS steps,” the coauthors reported.
Pre- and post-baseline disability trajectories “were highly variable,” they wrote. “No associations between the pre- and post-baseline trajectories were identified.”
“Lower relapse rates and greater time on higher-efficacy disease modifying therapy after reaching EDSS steps 3, 4, and 6 are associated with a decreased risk of accumulating further disability,” the team wrote—supporting administration of higher-efficacy therapy such as natalizumab, fingolimod, alemtuzumab, dimethyl fumarate, cladribine, rituximab, or mitoxantrone.
Dr. Kalincik disclosed financial support from Novartis, Merck, and Biogen. MSBase receives support from Merck, Merck Serono, and Biogen, Novartis, and Genyzme.