Stopping DMT use tied to greater long-term disability in MS database

People with multiple sclerosis (MS) who discontinue a disease-modifying treatment are more likely to have greater long-term disability than patients who continue with such therapies or go untreated, a registry database study reports.

Findings also suggest that patients who self-report better mobility early in their disease course also tend to have less disability in the long run.

The study, “Disease-modifying treatment, long-term outcomes and transition to progressive multiple sclerosis: data based on the New York State MS Consortium,” was published in the Journal of Neurology.

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Registry data study into MS disability over time and patterns of DMT use

Disease-modifying treatments, or DMTs, are anti-inflammatory medications shown in clinical trials to alter the course of MS, lowering the risk of disease activity and slowing disability worsening.

The increasing availability of DMTs over the last decades has changed disease trajectories and long-term outcomes for most people with MS. But studying how these have been evolving, and which factors are predictive of long-term outcomes in the presence of treatment, requires large amounts of data collected over long periods of time.

A team of scientists in the U.S. analyzed data covering 1,893 people with MS who were followed as part of the New York State MS Consortium since 1996.

Patients were divided into four groups according to patterns of DMT use: 41% were on a DMT consistently over the course of follow-up, 36.6% were not on a DMT when they entered the study but started or re-started DMT treatment during follow-up, 12% never used a DMT, and 10.4% were on a DMT when they entered the study but stopped treatment over follow-up.

Patients who never used a DMT or who discontinued tended to be older than those in the other groups, the researchers noted. Compared with the other three groups, a significantly greater proportion of patients who discontinued also reached significant disability or needed aids to walk even short distances over a median follow-up time of 6.9 years.

Using the available data, the researchers constructed statistical models to compare the risk of disability progression in each of these four groups.

They began by calculating the risk of reaching a score of at least 4 on the Expanded Disability Status Scale (EDSS). This EDSS score indicates that an individual has significant disability but no substantial problems walking.

Stopping a DMT tied to five times higher risk of EDSS score of 4

Results indicated that MS patients who discontinued a DMT were more than five times as likely to reach a sustained EDSS score of 4, compared with patients who had never been on a DMT. Patients on continuous treatment or who started DMT treatment during follow-up were more than twice as likely to reach an EDSS score of 4, compared with those who never used a DMT.

A finding of best disability outcomes in people who never used a DMT may seem counter-intuitive, the team noted. But they likely are explained by the phenomenon of confounding by indication, in which patients never given treatment usually are those with very mild disease — so it makes sense that they would also have mild disability outcomes.

Conversely, patients experiencing more severe disability would be more likely to be recommended for a DMT.

Analyses looking at the risk of reaching an EDSS score of 6 — meaning that the person needs an aid like a cane or crutch to walk 100 meters — showed similar patterns, with a notably increased risk among patients who discontinued treatment, and the lowest risk among patients who never had treatment.

These patterns also were similar when looking at the risk of transitioning from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS). Most patients initially have RRMS, which is marked by flares or relapses where symptoms suddenly worsen, followed by periods of remission where symptoms ease or disappear entirely. SPMS is defined by continuously worsening symptoms even when relapses don’t occur.

In the study, RRMS patients who stopped treatment were 4.7 times more likely to transition to SPMS than patients who had never been on treatment. Those who received continuous treatment or restarted a DMT during follow-up also were nearly four times more likely to transition than never treated patients.

Still, fewer than 1 in 5 of these patients reached an EDSS score of 6 or transitioned to SPMS over nearly two decades of follow-up, the scientists highlighted.

“After 17 years since symptom onset, less than 20% of [people with] MS experience disease progression to significant physical disability … and transition to SPMS,” they wrote.

Both these analyses also indicated an increased risk of reaching a higher EDSS score among patients who were older or had more severe disability when they entered the study. Male sex also associated with an increased risk of reaching more severe disability scores. These findings are in line with previous studies on the risk of MS progression, the team noted.

The risk of sustained high EDSS scores was significantly lower among patients who self-reported better mobility at the study’s start.

“Outside of the established risk factors of male sex, higher age at symptom onset and higher disability levels in the early MS period, our analysis also demonstrated that early acquisition of [patient-reported outcome]-based measures can help towards risk stratification,” the scientists wrote.