#MSVirtual2020 – Long DMT Exposure May Delay Disability Progression, Wheelchair Use

Longer exposure to disease-modifying therapies (DMTs) may delay disability progression and the time until people with primary progressive multiple sclerosis (PPMS) require the aid of a wheelchair, an Italian registry-based study found.

The study also suggests that starting treatment with DMTs — medications that reduce the activity of the immune system — at a younger age, and shortly after disease onset, can improve patients’ long-term clinical outcomes.

The findings were presented at MSVirtual2020 by Mattia Fonderico, MD, from the University of Florence, in Italy, in an oral presentation titled “Disease modifying treatment may delay time to wheelchair in primary progressive multiple sclerosis: a real-life cohort” (abstract #PS05.03).

The joint meeting, held online Sept. 11-13, was the 8th for the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

With the exception of Ocrevus (ocrelizumab), the first therapy approved by the U.S. Food and Drug Administration for PPMS, there are scant options for treatments for this form of multiple sclerosis (MS).

“Treatment options in primary progressive multiple sclerosis (PPMS) are lacking, as randomized clinical trials failed to show efficacy in reducing disability progression in this patient population,” Fonderico said.

“However, some recent results highlighted that a sustained exposure to DMTs, especially when administered close to disease onset and at a younger age, may exert a protective role reducing the risk of disability,” he added.

To investigate whether DMTs could be effective at slowing disability progression in PPMS, Fonderico and his colleagues reviewed real-world clinical data from 1,214 PPMS patients whose records were part of an Italian MS registry.

All patients selected for inclusion in the analyses had completed a minimum of three evaluations to assess the severity of their disability and were followed over the course of at least three years. The severity assessments were based on the expanded disability status scale (EDSS), which quantifies disability in multiple sclerosis and monitors changes in the level of disability over time.

Statistical analyses — adjusted to take into account the patients’ age, sex, and other clinical variables — were used to assess the impact of DMT exposure on each individual’s risk of reaching an EDSS score of 7 or higher. Such a score corresponds to a level of disability that requires patients to use a wheelchair to move around.

Among the PPMS patients analyzed were 671 women and 543 men, with an average age of 48.7 at the study’s start. In all, 626 (52%) received treatment with a DMT during follow-up.

DMTs evaluated in the analysis included interferons, monoclonal antibodies, glatiramer acetate (sold as Copaxone among other brand names), dimethyl fumarate (sold as Tecfidera among others), Aubagio (teriflunomide), Mavenclad (cladribine), and Gilenya (fingolimod).

The median EDSS score in the whole population at baseline (the analysis’ start) was 4.0, which corresponded to a significant level of disability but indicated that patients were self-sufficient and able to walk unaided much of the day.

After a mean follow-up of 11.7 years, 539 patients (44%) had reached an EDSS score of 7.

Initial analyses that looked at DMT effects as a dichotomous variable — meaning yes or no in terms of having an effect — failed to find a link between DMT exposure and the risk of disability progression.

However, subsequent analyses that took into account treatment timing, specifically earliest treated versus untreated, and DMT exposure — most exposed versus untreated — found that longer exposure to DMTs was associated with a significantly lower risk of achieving an EDSS score of 7.

Patients who had been exposed to DMTs for a longer period of time (more than 7.51 years) tended to be younger by the time they initiated treatment (mean of 44.3 years) than those who had shorter exposure to therapy (mean of 47.1 years in those exposed for 0.1 to 2.44 years).

These individuals also started treatment with DMTs sooner — closer to the time of disease onset, at a mean of 6.8 years — than those who were exposed to DMTs for a shorter period of time (mean of 10.2 years in those exposed for 0.1 to 2.44 years).

Overall, the results suggested that in this Italian population of PPMS patients, “longer exposure to DMTs delayed time to wheelchair [EDSS 7],” Fonderico said.

“Moreover, our analysis suggested that treating younger patients and reducing the delay of treatment initiation may improve the patients’ long-term disability outcomes,” he added.

According to Fonderico, future studies are needed to evaluate the long-term safety of DMTs in order to maximize their benefit-risk balance.