#ECTRIMS2018 – DMTs Slow Down Disability Progression in SPMS Patients with Ongoing Relapses, Analysis Shows

Treatment with disease-modifying therapies (DMTs) may benefit patients with secondary progressive multiple sclerosis (SPMS) who are actively experiencing relapses, as they can slow the disability’s worsening, a new analysis of an MS patient registry shows.

Patients who transition early from relapsing-remitting MS (RRMS) to SPMS and those with frequent relapses show a faster accumulation of disability, the study also reveals.

The study, “Determinants of disability accumulation in secondary-progressive multiple sclerosis” was presented Oct. 10 at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Berlin, Germany.

The presentation was given by Nathaniel Lizak, from the Clinical Outcomes Research Unit at The University of Melbourne in Australia, and was part of a scientific session titled “How real-world data can inform treatment decisions.”

SPMS is a second stage of MS which follows RRMS. Most patients diagnosed with RRMS will eventually transition to SPMS, a stage marked by progressive worsening of neurological function and increase in disability.

Before the introduction of DMTs, studies estimated that 50% of those with RRMS would transition to SPMS within 10 years, and 90% within 25 years. Although doctors and researchers agree that these medications are able to slow down MS progression, there is little data on the extent of their clinical benefit in delaying conversion to SPMS.

Over time, SPMS can be either active (with relapses and/or evidence of new MRI activity) or not active, as well as with progression (disease worsening) or without progression. But the disease course is unique for each SPMS patient.

Contrary to research in RRMS, the factors influencing disability accumulation in patients with SPMS remain poorly understood.

To investigate these factors, researchers conducted a retrospective study to evaluate which variables affect the rate of disability progression during SPMS, including the use of DMTs.

Researchers reviewed demographic and clinical data of 1,622 patients diagnosed with SPMS, from an international MS patient registry called MSBase.

All patients had records of disability follow-up over 24 months or less before diagnosis, until at least 12 months after diagnosis of SPMS.

The disability slope—  how fast patients’ disability accumulated over time — was quantified by measuring changes in the Expanded Disability Status Scale (EDSS), a score based on specific examinations (including motor, neurological and sensory) made by a neurologist.

The types of DMTs used by patients were recorded and categorized as:

Low efficacy, including several injectable medications;

Medium efficacy, including Gilenya (fingolimod) and Tecfidera (dimethyl fumarate);

High efficacy, predominantly Tysabri (natalizumab).

Of the 1,622 patients with SPMS, 662 had relapses throughout disease course, while 960 had not. Patients were grouped by the presence or absence of relapses, and analysed in separate models.

For all patients, those with a lower disability score at the time of SPMS onset or a higher relapse rate at that disease stage tended to accumulate disability faster.

Early use of DMTs, defined as four or more years before SPMS diagnosis, while patients were still in the RRMS stage, was not associated with how fast their disability got worse after SPMS onset.

But for those with relapses, the use of a DMT was linked with a lower disability slope, regardless of the class of DMT used. Also, among patients with ongoing relapses, those who were older and took longer to convert to SPMS were found to be associated with a slower disability progression.

“Relapses during SPMS contribute to ongoing disability accumulation,” Lizak said. 

In contrast, the rate by which disability accumulated did not seem to be influenced by the same factors in SPMS patients without relapses.

Overall, according to Lizak, in SPMS patients with relapses, a greater DMT use is “associated with a reduction in long-term disability accumulation,” suggesting that “relapses are a suitable treatment target in SPMS.”

Although in randomized controlled trials “most DMTs failed to show benefit during the progressive phase of SPMS,” researchers said, “Our observations justify continuing DMT use in SPMS patients who are actively relapsing. Earlier conversion to SPMS predicts subsequent faster disability progression.”