Early Use of Tysabri Treatment Linked to Greater Benefits

Multiple sclerosis (MS) patients who started taking Tysabri (natalizumab) long after their diagnosis were found to have worsened disease progression. But those who began using it earlier showed less aggravated clinical and radiological outcomes of the disease than participants who started treatment later, a study showed.

The study, “Benefits of early treatment with natalizumab: a real-world study,” was published in Multiple Sclerosis and Related Disorders. The work was supported by Biogen, which markets Tysabri, and seven of the 12 study’s authors were affiliated with the company.

Over the past several years, diverse disease-modifying therapies (DMTs) have been introduced for treating MS, Tysabri being one of them. It was approved in the U.S. in 2004.

“Ideally, MS should be diagnosed promptly and treated early,” the researchers wrote. “Over time, neurologists developed a consensus that DMTs should be used in most patients beginning soon after diagnosis.”

But physicians differ in their practices because there is no conclusive data about whether initiating high-efficacy DMTs such as Tysabri soon after a diagnosis is more beneficial for preventing or delaying disease progression. A common approach has been to start with a less potent treatment and move to high-efficacy DMTs for those who show clinical worsening.

Nonetheless, “the proper intensity of disease treatment at onset, the selection of individual DMTs, and the sequencing of DMTs are ongoing areas of research,” the researchers wrote.

Early Tysabri infusion vs. late treatment

To study the impact of early versus late start of high-efficacy DMTs, researchers looked at the clinical and imaging information of patients taking Tysabri.

The study included data from the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) and from Tysabri Outreach: Unified Commitment to Health Prescribing Program (TOUCH), which is designed to regulate prescriptions for Tysabri due to the increased risk of it causing progressive multifocal leukoencephalopathy, a rare brain infection that can be deadly or lead to severe disability.

The TOUCH registry provided an accurate time range between the age of MS diagnosis and the first Tysabri infusion. The MS PATHS provided data collected during routine office visits, including MRI scan results and clinical outcomes based on the multiple sclerosis performance test (MSTP). This test involves assessing disability by different tasks, including walking speed, processing speed, and manual dexterity.

In total, 661 MS patients met the study criteria, having participated in MS PATHS and having available TOUCH data. All were 18 or older when the first Tysabri infusion was applied, had at least one MS PATHS visit after the first treatment, and an adequate testing from MSTP. They also had a diagnosis that dated from 1994 or later (after the introduction of MS DMTs) and an interval of 20 years or less between their diagnosis and the first Tysabri infusion.

Of these 661 patients, 441 also had MRI results available.

The analysis showed patients with a longer time from diagnosis to the first Tysabri infusion showed more aggravated clinical and imaging outcomes — worse walking speed, manual dexterity, and a lower processing speed, which measures cognitive ability and is the time it takes to do a mental task. With MRI outcomes, later treatment was tied to increased brain atrophy and a bigger T2 lesion volume (the overall lesion load, both active and inactive MRI lesions).

Another group of participants (424 patients) diagnosed with MS in 2006 or later was included. This group also showed aggravated MS symptoms with walking speed, processing speed, and manual dexterity with a longer gap from diagnosis to starting Tysabri treatment. The differences were less robust than in the first group (diagnosed in 1994 or later), with brain atrophy and T2 lesions not showing a significant association with when Tysabri was initiated, however.

Changes in treatment patterns

The researchers hypothesized that this might be due to practice patterns that have evolved. “Starting in 1994, MS DMTs were introduced and were increasingly used over time. By 2006, standard practice involved treating most patients with an MS DMT and starting treatment early after diagnosis,” the research team wrote.

A narrower disease duration upon data collection and a shorter time range from diagnosis to first Tysabri treatment might explain the different results.

The researchers concluded that “later initiation of high-efficacy treatment is associated with worse long-term outcomes,” and that “high-efficacy DMT may have greater benefit when started earlier in MS patients.”

“There is a window of opportunity to prevent disability accumulation,” they said, noting that the “results provide a rationale for randomized controlled trials to further assess the impact of early highly-effective DMT use versus later escalation of therapy.”

In fact, two large trials are currently ongoing to address this question — TREAT-MS (NCT03500328) and DELIVER-MS (NCT03535298). Both are recruiting participants.

According to the team, “these two complementary studies will provide class I evidence on the topic of whether to use aggressive therapy earlier rather than maintaining the standard practice of treating with less aggressive therapy and escalating if needed.”