Patients started early on Tysabri are less likely to relapse, study finds

People who start treatment with Tysabri (natalizumab) soon after being diagnosed with multiple sclerosis (MS) are at a lower risk of relapse in the long term compared with patients who start on less effective disease-modifying therapies (DMT), a study has found.

Patients on Tysabri, an antibody-based therapy, also experienced higher rates of disability improvement over the long term.

The findings add to accumulating evidence that early treatment with a high-efficacy DMT may protect patients from irreversible nerve damage and bring about better long-term outcomes for people with MS.

The study, “Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies,” was published in Therapeutic Advances in Neurological Disorders. It was funded by Biogen, which markets Tysabri.

MS is a progressive disease that occurs when the body’s immune system wrongly attacks the protective covering of nerve fibers in the brain and spinal cord, leading to accumulating neurological damage and disability.

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In the past, patients usually started on moderate-efficacy DMTs

In previous years, MS treatment usually started with a moderate-efficacy DMT, which are less effective than newer therapies but generally have a better safety profile. Patients would then switch to more effective therapies if they continued to have signs of disease activity.

However, accumulating evidence indicates that delaying treatment with these higher efficacy therapies may contribute to disability accumulation that can no longer be reversed. Thus, starting highly effective DMTs as soon as possible after an MS diagnosis may be the best option to prevent disability worsening and improve long-term outcomes.

Tysabri is a high-efficacy therapy that works by preventing immune cells in the bloodstream from reaching the brain and spinal cord, thereby reducing inflammation and damage. It’s approved for adults with relapsing forms of the disease, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).

However, limited research is available that compares the use of Tysabri versus lower efficacy DMTs as a first-line therapy in these patients.

To address that, researchers set out to examine long-term outcomes for patients who were started on Tysabri versus a less effective DMT within one year of their diagnosis, and remained on it for at least six months. Data came from MSBase, a large international registry for MS and other neurological diseases.

As of November 2020, a total of 360 patients had been started on Tysabri and 12,033 on a less effective therapy, namely an interferon beta therapy, glatiramer acetate (sold as Copaxone among others), Aubagio (teriflunomide), or Tecfidera (dimethyl fumarate).

The groups were matched for age, disease duration, number of relapses in the prior year, relapses requiring steroid treatment or hospitalization, and disability levels, leaving a total of 355 in each group for the final analyses.

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Patients had minimal to mild disability at the start of treatment

In both groups, the median Expanded Disability Status Scale (EDSS) score at the start of treatment was 2.5 points, indicating minimal to mild disability. Higher scores indicate more severe disability.

Patients were then followed for an average of about five years, although data was available for some patients for up to 15 years.

Results showed patients who started on Tysabri were less likely to experience a relapse over that period compared with those on a less effective DMT. The mean number of relapses per year was 0.08 for Tysabri and 0.191 for the other therapies, a significant difference, and researchers also estimated that the risk of a first relapse was 48% lower with Tysabri.

Disability worsening, defined as an increase in EDSS scores that was sustained for at least six months, was not different in the two groups. However, those who started treatment with Tysabri were 55% more likely to experience a first disability improvement event over 15 years, or a lessening in disability.

During the follow-up period, 67.8% of patients discontinued Tysabri and 82.3% stopped the lower efficacy treatment. The most common reason for discontinuing Tysabri was a scheduled stop — often employed to reduce the risk of progressive multifocal leukoencephalopathy, a rare brain infection that can occur during treatment with Tysabri — while a lack of improvement was most commonly cited in the lower efficacy treatment group.

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Patients on Tysabri less likely to switch therapy

Patients on Tysabri were less likely to switch therapy, but when they did, it often was to another high-efficacy DMT. In turn, those on the lower efficacy DMTs were more likely to switch to another moderate-efficacy drug. During a second switch, however, more than half (55.7%) switched to a high-efficacy DMT.

Notably, data from a subgroup of patients who started on a moderate efficacy DMT and transitioned to a higher efficacy one within three years still had higher relapse rates and were more likely to experience disability worsening than those who started on Tysabri early on.

“A treatment strategy with early initiation of [Tysabri] produced long-term benefits in comparison with early initiation of [lower efficacy therapies], regardless of subsequent potential switches in therapy,” the researchers wrote.

“Though some patients may not be good candidates for [Tysabri] treatment because of safety concerns, the introduction of other high-efficacy DMTs to the MS treatment landscape has expanded treatment options, and a shift away from the escalation paradigm is increasingly adopted,” they concluded.