Earlier Treatment With Disease-Modifying Therapies Decreases Risk of MS Progression

Treating patients with relapsing-remitting multiple sclerosis (MS) early with disease-modifying treatment (DMT) can reduce the risk of conversion to secondary progressive MS, according to new research published in JAMA.¹

A majority of patients (80%) with relapsing-remitting MS convert to secondary progressive MS within 2 decades of onset it they are left untreated. However, there has been no rigorous definition of secondary progressive MS, and many previous studies have examined the association of interferon b and glatiramer acetate and conversion to secondary progressive MS.

The authors sought to determine the use of DMTs, and when they are used, and their association with risk of conversion to secondary progressive MS. Because there has been no rigorous definition, the authors used a new validated definition of secondary progressive MS as published in Brain.²

"Most of the therapies that we use to treat MS have no effect once people have converted to secondary progressive MS," Tomas Kalincik, MD, PhD, one of the study leads, said in a statement. "This study shows us how important it is to treat relapsing MS early and proactively."

The authors analyzed data on patients with relapsing-remitting MS who were beginning DMTs or clinical monitoring at 68 neurology centers in 21 countries. Patients analyzed had a minimum of 4 years’ follow-up.

The study included 1555 patients. While patients initially treated with glatiramer acetate or interferon b had a lower risk of conversion to secondary progressive MS than untreated patients (hazard ratio [HR], 0.71; 95% CI, 0.61-0.81; P&thinsp; <.001), patients treated with fingolimod, alemtuzumab, or natalizumab had an even lower risk of conversion than patients initially treated with glatiramer acetate or interferon b (HR, 0.66; 95% CI, 0.44-0.99; P&thinsp; = &thinsp;.046).

“The risk of conversion was significantly lower for early treatment than for late treatment: either in the case of starting glatiramer acetate or interferon beta within 5 years of disease onset vs later commencement; or when escalating from glatiramer acetate or interferon beta to fingolimod, alemtuzumab, or natalizumab within 5 years of disease onset vs later escalation,” the authors explained.

The researchers highlighted a number of limitations, including the observational design of the study, which makes the study unable to attribute causality and makes it difficult to distinguish between prevention and delay of conversion. Another limitation was the different baseline demographics for each DMT cohort, which led to differing matched untreated cohorts and follow-up durations. The study also did not assess the risks associated with DMTs.

“These findings, considered along with these therapies’ risks, may help inform decisions about DMT selection,” the authors concluded.

In an accompanying editorial³ in JAMA Neurology, Ari J. Green, MD, MCR, who is the associate editor of the journal and a neurologist at the University of California, San Francisco, wrote that study is an important addition to the growing mountain of evidence that intervention with immunotherapeutic agents can have a favorable effect on long-term progression of MS.

According to Green, the findings are timely since the first treatment for people with primary progressive MS was approved in 2017 and another is expected to be considered in 2019. “…The moment is ripe to think about treatment of progressive MS and both the benefits and limits of existing approaches,” he wrote.

1. Brown JWL, Coles A, Horakova D, et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA. 2019;321(2):175-187. doi: 10.1001/jama.2018.20588.

2. Lorscheider J, Buzzard K, Jokubaitis V, et al; MSBase Study Group. Defining secondary progressive multiple sclerosis. Brain. 2016;139(pt 9):2395-2405. doi: 10.1093/brain/aww173.

3. Green AJ. Potential benefits of early aggressive treatment in multiple sclerosis [published online January 15, 2019]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.4932.

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