Early Use of High-efficacy DMTs of Long-term Benefit to MS Patients, Real-world Study Reports

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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DMTs and MS regimens

Multiple sclerosis (MS) patients given intensive disease-modifying therapies early in their disease course have more favorable long-term outcomes than those treated with an escalating regimen, real-world data shows.

The study, “Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis,” was published in the journal JAMA Neurology.

Disease-modifying therapies, or DMTs, are pharmaceutical agents that mainly act on the inflammatory features of MS, and can be divided according to the degree of efficacy in preventing relapses.

DMTs with the highest efficacy rates, however, can pose safety issues, and their use is associated with strict monitoring and, occasionally, the need for hospital admission. For this reason, current medical guidelines recommend high-efficacy DMTs only for aggressive MS cases with a poor prognosis.

People with milder MS typically escalate in their use of DMTs, starting with the safest and moving to more efficient therapies if needed, according to disease progression.

Researchers in the U.K. evaluated long-term outcomes — defined primarily as the change in disability scores at about five years of treatment — in patients treated early with an intensive DMT approach compared to those given escalating doses.

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Lemtrada (alemtuzumab, marketed by Sanofi Genzyme) and Tysabri (natalizumab, marketed by Biogen) are considered high-efficacy DMTs, while interferons (like Avonex, marketed by Biogen), Copaxone (glatiramer acetate, marketed by Teva Pharmaceuticals), Tecfidera (dimethyl fumarate, marketed by Biogen), and Aubagio (teriflunomide, marketed by Sanofi Genzyme) are categorized as moderate agents.

The analysis included 592 MS patients (mean age of 27 at symptom onset) from a population-based cohort in the United Kingdom. Among them, 82 percent were prescribed a DMT — 17.6 percent (104 patients) were given a high-efficacy agent, and 82.4 percent (488 patients) began with moderate treatment. Within the moderate group, 11.9 percent (58 patients) went on to use a high-efficacy therapy after the first therapy.

People on high-efficacy DMTs were mostly treated with Lemtrada (67%) compared with Tysabri (33%). Those patients given high-efficacy DMT as second-line therapy were more frequently prescribed Tysabri (74%) than Lemtrada (26%).

Patients remained in the same therapy group for a median time of two years, although a patient who started with a moderate efficacy therapy took a median of 2.4 years to move to a high-efficacy treatment plan.

Post-treatment results showed that the annualized relapse rate (AAR) for MS patients was 0.16 in the escalation group, and zero in the intensive approach group.

Baseline, or study’s start, scores on the Expanded Disability Status Scale (EDSS), used to monitor MS severity (the higher the EDSS score, the worse is the patient’s disability), were 4.5 among people in the high-efficacy regimen group, and 3.5 in the moderate regimen group.

However, when looking at the five-year follow-up EDSS scores, researchers saw that patients in the moderate group had a greater change that those treated with a high-efficacy agent — a significant change in EDSS scores of +1.2 versus +0.3, respectively.

“Those who received high-efficacy treatment initially had a smaller increase in Expanded Disability Status Scale score at 5 years vs those who first received moderate-efficacy disease-modifying therapy,” the researchers wrote.

Time to “sustained accumulation of disability” or SAD — defined as a six-month or longer sustained increase in an EDSS score of 1.5 if baseline was 0, and an increase of 1.0 if baseline was 1.0 to 5.5 — “appeared delayed in those receiving EIT [early intensive treatment] (6.0 years) compared with those who had an escalation approach (3.1 years),” the study noted. This difference, however, was not statistically significant when other factors were taken into account.

Safety in the use of high-efficacy agents, namely Lemtrada, presented some complications, with 87% of the patients developing infusion-related adverse events, and 47% developing autoimmunity conditions, but no infections or treatment-related deaths were observed. No serious adverse events were reported in patients given Tysabri.

In patients given moderate-efficacy DMTs, seven (1.4%) serious adverse events were reported but no treatment-related deaths.

Overall, the team concluded that “in a real-life setting, long-term outcomes were more favorable following early intensive therapy vs first-line moderate-efficacy DMT.”

According to the researchers, their “study undermines the prevalent belief that an escalation approach represents a lower-risk strategy to MS treatment and suggests that in the real-world, an escalation approach to DMT may be inadequate to prevent unfavorable long-term outcomes.”

Given these results, the researchers emphasized the need “for a prospective clinical trial to compare disease-modifying therapies.”

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