Tysabri found to be safe and effective in real-world Danish study

Tysabri (natalizumab) is generally safe and effectively lowers disease activity in people with multiple sclerosis (MS), according to a real-world study of patients over a 13-year period in Denmark.

“Most patients treated with [Tysabri] are clinically stable with few adverse events,” researchers wrote.

In more recent years, doctors tended to prescribe the therapy to patients who were younger and with less active disease, which is in line with a general increase in the use of high-efficacy therapies early on in the disease course.

The study, “Natalizumab treatment of multiple sclerosis — a Danish nationwide study with 13 years of follow-up,” was published in Multiple Sclerosis and Related Disorders.

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Tysabri is an antibody-based therapy for relapsing MS

Tysabri is a widely used antibody-based therapy for relapsing forms of MS. Approved for nearly two decades in the U.S. and Europe, the therapy has ample clinical trial data supporting its ability to lower relapse rates, reduce disability progression, and prevent new lesions in MS patients.

However, trial data also indicated that Tysabri can increase a person’s risk for progressive multifocal leukoencephalopathy (PML) — a rare and life-threatening brain infection — which has led many countries to impose restrictions on who can take the therapy and how they should be monitored.

Still, “while [randomized controlled trials] are gold-standard in establishing the clinical efficacy and safety of therapies, they might not reflect the clinical use of the treatment,” the researchers wrote.

As such, the researchers set out to examine the real-world safety and effectiveness of Tysabri among virtually all patients treated with the therapy in Denmark from June 2006, when it was first marketed in the country, to April 2020.

Healthcare records from 2,424 patients included in the Danish MS Registry were examined, including 701 men and 1,723 women, who had a median age of 38.4 when they started Tysabri treatment. In total, 961 patients initiated treatment from 2006 to 2011; 1,252 from 2012 to 2018; and 211 from 2019 to 2020.

Most patients treated with [Tysabri] are clinically stable with few adverse events.

Tysabri recently being prescribed to younger patients with less disability

Notably, the prescription pattern of Tysabri changed over time, with those starting the therapy in more recent years being younger, with less disability and fewer relapses. They were also more likely to have never used other MS therapies.

“These changes in the prescription pattern may reflect an increased focus on the potential benefits of high efficacy therapy in the early stages of disease — particularly in patients with high disease activity,” the researchers wrote.

Patients were treated for a median of 2.7 years, during which time their clinical status was monitored using the Expanded Disability Status Scale (EDSS), a 10-point scale in which higher scores reflect more severe disability.

Confirmed disability worsening and confirmed disability improvement were defined as an increase or decrease in EDSS scores, respectively, that was confirmed at a visit at least six months later.

Of 1,774 patients with available data, 352 (19.8%) experienced confirmed disability worsening 24 weeks after starting on Tysabri, and 277 of these events (15.6% of patients) were sustained until the patients’ last available disability assessment, which happened at a mean of 2.4 years after starting treatment.

Additional analyses indicated that patients at the highest risk for clinical worsening were men, those who developed MS at a younger age or started Tysabri at an older age, and those with a lower EDSS at the start of treatment.

On the other hand, 589 events of confirmed disability improvement, indicating a sustained easing in disability, occurred. Of them, 421 were sustained until the last available EDSS score (24.5% of patients).

Those most likely to achieve disability improvement included women, patients older at MS onset, patients younger when they started on Tysabri, those who hadn’t received prior MS therapies, and those with a higher EDSS score at treatment initiation.

Ultimately, after 13 years of follow-up, 36% of patients had experienced a confirmed clinical worsening, whereas 47.7% had experienced a confirmed improvement.

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Relapse rates reduced for patients on Tysabri

In the year before starting Tysabri, the annualized relapse rate was 1.11, indicating that patients had on average 1.11 relapses per year. This rate was reduced to 0.3 while patients were on Tysabri — a 72% reduction in relapses. Among those who stopped Tysabri, 13.5% relapsed within six months after stopping.

For patients with available MRI data, new and enlarging or active brain lesions weren’t common, with 6.8% of patients showing them within two to 14 months after starting treatment. That declined to 2.7% at 26-38 months (about 2-3 years) after starting treatment.

Over the course of follow-up, 14% of patients reported side effects, about three-quarters of which were cephalalgia, or head pain. Three or fewer cases of PML were reported.

By April 2020, 915 patients remained on Tysabri and 1,509 had stopped using it, reflecting a 62.3% discontinuation rate.

The most common reasons for stopping treatment included presence of antibodies against the John Cunningham virus, which causes PML (41%); pregnancy (11%); antibodies against Tysabri (9.3%); disease activity (9%); and adverse events (9%).

Overall, the findings reflect a “high clinical effectiveness” of Tysabri, which is consistent with clinical trial data and previous observational reports.

The data “provide strong real-world evidence of efficient suppression of clinical relapses, EDSS worsening and [MRI] activity” with Tysabri treatment, the team concluded.