No Neuron Damage Increase With 6-week Switch to Tysabri: Study
Individual variations in biomarker levels appeared to be influenced by age
Switching from a standard monthly course of Tysabri (natalizumab) to an extended-interval dosing administered every six weeks does not seem to increase neuronal damage in people with multiple sclerosis (MS), a study found.
While individual blood levels of neurofilament light chain (NfL), a biomarker of nerve damage, did not fluctuate much over a year, older patients were more likely to have at least one NfL measurement that deviated significantly from the average than younger patients, data showed.
The findings suggest that “the best utility of sNfL measurements is for individual longitudinal follow-up of younger adult age,” the researchers wrote.
The study, “No increase of serum neurofilament light in relapsing-remitting multiple sclerosis patients switching from standard to extended-interval dosing of natalizumab,” was published in Multiple Sclerosis Journal.
Biogen‘s Tysabri is an approved antibody-based therapy for relapsing forms of MS that works to prevent immune cells from accessing the brain, thereby reducing the inflammatory response that causes damage in MS. The medication is administered via intravenous (into-the-vein) infusions and the approved dosing schedule is 300 mg every four weeks.
Because it blocks the activity of the immune system in the brain, Tysabri is linked with an increased risk of progressive multifocal leukoencephalopathy (PML), a rare and serious brain infection that can be deadly or severely debilitating.
According to the research team, the standard dosing interval was originally selected to ensure the therapy was bound to at least 70%–80% of its target receptors on immune cells. But more recent studies have shown that a lower receptor occupancy can still block immune cell migration, which could underlie the continued effectiveness of less frequent dosing, the team suggested.
As small signs of inflammation and neurodegeneration may escape conventional monitoring approaches, a team of researchers in Sweden decided to use a more sensitive marker of nerve damage — NfL levels in circulation — to determine if switching to an extended dosing schedule was indeed not increasing disease activity.
The team enrolled 70 relapsing-remitting MS (RRMS) patients from the Sahlgrenska University Hospital, Gothenburg, Sweden. Eligible participants had been receiving a 300 mg dose of Tysabri, given every four, five, or six weeks, for at least a year and had no signs of relapses or new lesions in the six months before starting treatment.
Participants were split into two groups, based on their dosing schedule. One group of 45 patients had been receiving the standard every-four-week regimen and was switched to the extended dosing of every six weeks instead.
The other group included 25 people who had received the therapy at an extended 5–6 week interval. With the exception of one patient, all were then given the therapy every six months during the observation period.
Overall, 66 out of 70 participants (94%) showed no evidence of disease activity throughout the study, meaning they experienced no relapses, no increases in disability, and no new or enlarging lesions.
The remaining included one patient with a relapse and a new MRI lesion, and three who had disease progression and converted to a secondary progressive disease course during follow-up.
Blood samples were collected at regular intervals up to 48 weeks (nearly a year) after the switch to monitor NfL levels.
Results showed NfL levels in serum — the liquid portion of blood — remained similar and relatively stable in both groups throughout follow-up, including among the patients who had some form of disease activity.
Further analyses among those who switched from the standard to the six-week extended dosing revealed individual variations in NfL appeared to be influenced by age, but not by other clinical characteristics.
After adjusting for age, the team found that older people were much more likely to have NfL measurements above the normal levels for their age group, even in the absence of clinical or MRI signs of disease activity.
This suggests “NfL monitoring was most reliable for monitoring younger adult patients with RRMS,” the researchers wrote.
The data support previous findings that extending Tysabri dosing does not affect the clinical course of disease, the researchers wrote, noting, however, that it can’t be ruled out that serum NfL levels change beyond the one-year time frame, which could reflect slower, more chronic inflammatory processes.