Switching DMTs in MS found to impact relapse risk in real world

People with multiple sclerosis (MS) who switch between more than two disease-modifying therapies (DMTs) have a higher risk of relapses compared with those who never switch, regardless of how well these patients adhere to their prescribed medications, according to real-world study in Canada.

These findings are consistent with a greater number of treatment switches in individuals with a poor response to different therapies and/or higher disease activity, the researchers noted.

However, among patients who ever switched treatments, those who changed to second-line DMTs had a 56% lower risk of relapse after the switch compared with those who remained on a first-line DMT. That result suggests that higher-efficacy therapies can more effectively control relapses in these patients.

“This provides a strong rationale for escalating therapy among those who have relapses requiring intervention,” the team wrote.

The study, “Switching to second line MS disease-modifying therapies is associated with decreased relapse rate,” was published in the journal Frontiers in Neurology.

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Investigating treatment adherence in patients on DMTs

More than 20 therapies have been approved to date to reduce disease activity or slow the progression of MS, an inflammatory disease that affects the brain and spinal cord.

Generally, patients are treated according to an escalation strategy, in which they first receive a moderately effective, first-line DMT with a well-established safety profile. If patients to respond adequately to treatment, their healthcare team can then switch them to a more potent, second-line therapy.

While escalating to a more effective treatment is an well-established approach, past studies have failed to account for treatment adherence when comparing the efficacy of first-line and second-line therapies.

To address that, researchers at the University of Manitoba, in Canada, evaluated how DMT exposure — including treatment adherence and switches between different DMTs — impacted the risk of MS relapses in a real-world clinical setting.

The team examined data collected between 1999 and 2015 from two patient registries. One, the Manitoba Population Research Data Repository, at the Manitoba Centre for Health Policy (MCHP), includes health claims data from 98% of the population in that province, while the other, the Winnipeg MS Clinic Registry or MSCR, is the only specialty MS clinic in Manitoba.

At the time of the analysis, available first-line therapies in Manitoba included interferon-beta therapies, Copaxone (glatiramer acetate), Tecfidera (dimethyl fumarate), and Aubagio (teriflunomide). Second-line DMTs, in turn, included Gilenya (fingolimod) and Tysabri (natalizumab).

The study’s main goal was to determine the time to a first relapse requiring treatment. Such flare-ups generally are associated with sustained disability progression and are one of the criteria for accessing second-line therapies in Manitoba.

Researchers also analyzed how switching between DMTs affected the risk of relapse.

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Over 50% lower relapse risk seen for patients switching to higher-efficacy DMT

A total of 1,780 patients with relapsing forms of MS were included in the analysis. Of them, 1,510 patients were prescribed a DMT, while 270 never received treatment. Overall, patients who never received a DMT had developed MS about nine years later than the treated group (47.6 vs. 38.4 years) and had a lower number of treated relapses (22% vs. 45%).

The majority of those prescribed a DMT — fully three-quarters of the patients or 75.8% — had a good adherence to their prescribed treatment, as shown by a cumulative medication possession ratio (MPR) above 80%. MPR is a measure of the number of days a patient is stocked for their medication in a given period; it assesses if patients have enough supply to receive the medication as prescribed. Lower MPRs mean lower treatment adherence.

Also, more than half of treated patients never switched their prescribed DMT (63.6%), while 26.1% switched their medication once and 10.3% switched 2-4 times.

Statistical analysis demonstrated that being treated with a DMT was not associated with time to a first treated relapse. However, among patients treated with a DMT, those who switched between more than two DMTs had a markedly higher risk of treated relapses after switching when compared with those who never changed their treatment.

The reduced risk among patients who remained always on the same medication was independent of treatment adherence, the team found.

Escalation of DMT in [people with relapsing MS] is effective in reducing the rate of relapses among individuals with a history of treated relapses.

In a final analysis looking at the kind of DMT to which patients switched, the results showed that those who changed to a higher-efficacy drug had a 56% lower risk of experiencing treated relapses. That was compared with patients who either remained on their first-line therapy or switched to another first-line medication.

“Escalation of DMT in [people with relapsing MS] is effective in reducing the rate of relapses among individuals with a history of treated relapses,” the team wrote.

Further clinical trials are needed to assess whether “initial treatment with higher efficacy DMTs rather than an escalation approach improves outcomes in treatment-naïve individuals with a range of disease activity,” the study concluded.