ACTRIMS Session on MS Progression to Emphasize Continuing Treatment of Advancing Disease

Patricia Silva, PhD avatar

by Patricia Silva, PhD |

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The Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2016 starts today, Feb. 18, in New Orleans, Louisiana, and runs through Saturday, Feb. 20. The opening day’s Session 1, titled “Emerging Concepts in MS,” places special focus on cutting-edge studies on the pathogenic mechanisms in multiple sclerosis (MS), new measures of disease activity, and treatment options.

In this session, Nathaniel Lizak from the University of Melbourne and Monash University, will present potentially important data on the effects of immunotherapies in disability progression. His talk is titled, “Immunomodulatory therapy slows accumulation of disability in moderately advanced multiple sclerosis.

The research builds on data from the MSBase, a large international observational MS cohort study.

Three large previous studies have suggested that once disease trajectories reach a moderate stage — defined as the transition from Expanded Disability Status Scale (EDSS) phase three or four to six — the disease is at a new stage and driven by neurodegeneration. The implication is that once the disease reaches this phase, a therapy no longer has any effect on disease progression. The results of these earlier studies were, however, contradictory, and no analysis of variability had been performed.

The research team set out to investigate variability and predictability of the course of disability in moderately advanced MS. They also aimed to establish if it is possible to modify the accumulation of disability with immunomodulatory treatment.

Data was extracted from the MSBase and divided —relapse-onset MS patients into three groups based on their EDSS scores at a defined baseline. The researchers included data on patients who had reached an EDSS score of 3, 4, or 6, and analyzed patient data 12 months before this baseline through to outcome EDSS scores of 6 or 6.5. In total, 1,560 patients with EDSS scores of 3-6, 1,504 patients with scores 4-6, and 1,231 patients with scores 6-6.5 were included in the study.

Results showed that before and after the baseline time point, the course of disability was highly variable, and the researchers found no associations between pre- and post-baseline disability trajectories. They also noted that a higher rate of yearly relapses increased the risk of disability progression, and that inflammation is a key driver of disability in moderately advanced MS.

Also, patients who persisted shorter times on higher efficacy immunomodulatory treatment during each phase had an increased probability of reaching the outcome EDSS score. The team, however, could not prove these associations for the relapses and therapy before the baseline.

Higher efficacy therapies were defined as treatment with natalizumab (Tysabri), fingolimod (Gilenya), alemtuzumab (Lemtrada), dimethyl fumarate (Tecfidera), cladribine (Leustatin), rituximab (Rituxan), or mitoxantrone (Novantrone).

The study concludes that disability accumulation during moderately advanced MS is highly variable, and not dependent on how the disease developed at an earlier stage. The data also contradicts the practice of discontinuing treatment once MS patients have reached higher EDSS scores, by clearly showing that immunomodulatory treatment prevents disability accumulation.

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