Use of mild-to-moderate DMTs predicts switching to other DMTs

People with multiple sclerosis (MS) who start treatment with a mild-to-moderate efficacy disease-modifying therapy (DMT) were more likely to switch to another DMT, an analysis of the German MS Registry finds.

Starting a DMT between 2014 and 2017 was also a predictor of switching. Disease activity despite treatment was the most common reason to change DMTs.

“Our real-world registry study — indicating a high frequency of DMT switches due to insufficient disease control — supports a view that prospective, longer-term treatment strategy studies are needed,” the researchers wrote in “Treatment switches of disease-modifying therapies in people with multiple sclerosis: long-term experience from the German MS Registry,” which was published in Therapeutic Advances in Neurological Disorders.

DMTs suppress the immune-mediated attacks that drive MS. They are designed to reduce relapses from occurring and new lesions from developing, and slow disease progression. They can be broadly classified into mild-to-moderate efficacy (MME) and high-efficacy (HE) treatments. MMEs are older and generally less effective at preventing disease activity and slowing progression, but have fewer side effects. HEs are newer therapies that are more potent, but have a higher risk of side effects and can be more costly.

Historically, treating MS typically started with an MME and patients were then switched to HE DMTs if their disease activity worsened. This is still done, but recent evidence suggests that starting with an HE is generally the best way to prevent long-term disability accumulation.

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What predicts switching to a different DMT?

There are few comprehensive studies about switching DMTs in real-world settings, which are “essential to better understand the full range of therapeutic patterns and eventually to draw conclusions for the treatment of [people with MS] and also for initial treatment decisions,” wrote researchers in Germany who collected data from the German MS Registry to compare the demographic and clinical differences between 1,361 MS patients who stopped their first DMT and 1,361 age- and sex-matched patients who didn’t switch.

More than half of the switchers (55.5%) changed their first DMT within 1.5 years. A total of 917 (67.4%) participants switched once, 326 switched twice (24%), and 118 switched at least three times (8.7%).

The first DMT for most patients (77.1%) was an MME, the most common being glatiramer acetate (sold as Copaxone among others), Tecfidera (dimethyl fumarate), and interferon beta-based medicines.

DMT switchers changed treatment more often to an HE than to an MME (39.6% vs. 35.9%). About a fifth (19.2%) of the switchers stopped DMTs altogether. The reasons for discontinuing the first DMT were disease activity despite treatment (63.1%), side effects (17.1%), and the patient requesting it (8.3%).

After switching, second DMTs most commonly used were Gilenya (fingolimod), Zeposia (ozanimod), Ponvory (ponesimod), and Mayzent (siponimod), Tecfidera or Vumerity (diroximel fumarate), and Ocrevus (ocrelizumab).

Three factors predicted switching from the first DMT — using an MME as a first treatment, starting a DMT between 2014 and 2017, and spending less time on the first DMT.

Compared with the total study population, switchers spent much less time on their first DMT (mean, 3 vs. 1.7 years). Also, among switchers, the treatment duration was shorter for their first DMT than for subsequent ones. Patients who started a DMT between 2014 and 2017 and those who began with an HE DMT remained on their first DMT longer, however.

“Our Germany-wide, real-world study found that the majority of patients examined started with an MME DMT as initial therapy,” the researchers concluded. “This illustrates that a majority of initial treatment decisions follow an escalation approach, switching to an HE DMT when considered needed.”

The researchers said this is consistent with another finding, which “indicated that MS disease activity despite DMT use represented the most common reason for DMT switches.”