NEW ORLEANS—Disease progression during moderately advanced multiple sclerosis (MS) is amnesic to prior disease activity, according to researchers reporting at the ACTRIMS 2016 Forum. Lower relapse rates and greater persistence on higher-efficacy immunomodulatory therapy after reaching Expanded Disability Status Scale (EDSS) steps 3, 4, and 6 are associated with a decreased risk of accumulating further disability. “Highly effective disease-modifying therapy can mitigate the disability accrual after reaching confirmed EDSS steps of 3, 4, and 6,” said Nathaniel Lizak, BMedSc(Hons), MBBS, of Monash University in Clayton, Australia, and the University of Melbourne, and his research colleagues.
Nathaniel Lizak, BMedSc(Hons), MBBS
Three large cohort studies have previously examined factors influencing disability accumulation in moderately advanced MS, Dr. Lizak and colleagues noted, but these studies yielded contradictory conclusions. “The effect of therapy during this disease stage remains unclear,” the researchers said.
Dr. Lizak and colleagues sought to identify modifiers of disability trajectories in moderately advanced MS, including disease activity and immunomodulatory therapy during the early and moderately advanced stages of MS. They hypothesized that individual disability trajectories are not homogenous and can be predicted based on demographic and clinical characteristics.
The researchers analyzed epochs between EDSS steps 3 to 6, 4 to 6, and 6 to 6.5. Patients with relapse-onset MS, six-month confirmed progression to the initial EDSS step (baseline), and 12 months pre-baseline follow-up were identified in MSBase, a large international observational MS cohort study. Multivariable survival models examined the impact of relapse rate and proportion of time treated (prior to and during each epoch), age and disease duration at baseline, and progression to the outcome EDSS (6 or 6.5). Sensitivity analyses varying outcome definition and inclusion criteria also were conducted.
For the 3 to 6, 4 to 6, and 6 to 6.5 epochs, 1,560, 1,504, and 1,231 patients were identified, respectively. Pre- and post-baseline disability trajectories showed large coefficients of variance (0.85 to 0.92 and 1.95 to 2.26, respectively) and did not correlate. Probability of reaching the outcome EDSS was not associated with pre-baseline variables, but was increased by higher relapse rates during each epoch (hazard ratios, 1.58 to 3.07). Greater proportion of each epoch treated with higher-efficacy therapies was associated with lower risk of the outcome EDSS (hazard ratios, 0.27 to 0.68). These results were confirmed by sensitivity analyses.
“These observations justify treatment even after moderately advanced disability has been attained,” Dr. Lizak and colleagues concluded.