ECTRIMS 2023: Personalized dosing of Tysabri shows good efficacy

Interim data from ongoing clinical trial NEXT-MS presented at conference

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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A personalized dosing schedule for Tysabri (natalizumab) that aims to maintain blood levels of the drug above a certain threshold seems to be just as effective for controlling disease activity in relapsing-remitting multiple sclerosis (RRMS) as the approved every-four-week dosing schedule.

That’s according to interim data from an ongoing clinical trial called NEXT-MS (NCT04225312).

Alyssa Toorop, a graduate student at MS Center Amsterdam in the Netherlands, presented the findings at this year’s meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), in Italy.

Her talk was titled, “Prospective trial of natalizumab personalized extended interval dosing by therapeutic drug monitoring in relapsing remitting multiple sclerosis (NEXT-MS).”

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Tysabri is an approved MS treatment that works by blocking inflammatory immune cells from moving into the brain and spinal cord. The therapy is administered via infusions into the bloodstream, and according to the currently approved dosing schedule, these infusions should be given every four weeks.

While Tysabri can be very effective for controlling disease activity, the therapy also carries substantial safety risks — of particular concern, it can set the stage for a type of life-threatening brain infection called progressive multifocal leukoencephalopathy (PML).

Recently scientists have begun investigating whether Tysabri infusions could be given less frequently than the approved every-four-week schedule.

Theoretically, this might reduce the risk of PML and other side effects, as well as lower healthcare costs, without compromising the efficacy of the therapy. Some recent research has suggested that Tysabri is no less effective when given every six weeks.

Personalizing Tysabri dosing

The NEXT-MS clinical trial, sponsored by Amsterdam UMC, is testing a different strategy where Tysabri levels are measured in the blood, and a new infusion is given only once levels reach a pre-defined low point.

“In today’s modern world, it is possible to personalize almost anything. Then, isn’t it strange that when it comes to treatment with medication in multiple sclerosis, personalized therapy is often not an option,” Toorop said. “With the NEXT-MS study, we want to make treatment for patients using [Tysabri] more personalized, by measurement of individual drug concentrations.”

The study, conducted in 21 hospitals in the Netherlands, included 376 adults with RRMS who had been on a stable regimen of Tysabri for at least six previous infusions.

Participants were allowed to participate in one of three groups. One group (60 patients) preferred to continue on the standard dosing schedule of infusions every four weeks. In the other two groups, new infusions were given when levels of Tysabri in the blood declined to either 10 micrograms (mcg)/mL (251 patients) or a lower concentration of 5 mcg/mL. (65 patients).

Of note, the 5 mcg/mL group had stricter inclusion criteria, so patients in this group generally had less active disease before switching to the personalized dosing schedule.

Following patients in the trial

As of the most recent data collection, the majority of patients in NEXT-MS have been followed for more than a year.

In the 10 mcg/mL group, the median time between infusions ended up being five weeks, and most patients received infusions every four to six weeks. In the 5 mcg/mL group, median time between infusions was six weeks, with infusion intervals ranging from every four to every nine weeks. About one-third of patients in the 5 mcg/mL group were able to extend treatment intervals beyond six weeks.

Over the course of the study, the number of patients with new or enlarging lesions on MRI scans was low, with just a handful of patients in any of the three groups showing new activity.

“We saw no differences in radiological disease activity between all study groups,” Toorop said.

A comparison between data from the 10 mcg/mL group and previously-collected data from people given standard every-four-week dosing also showed no significant differences in terms of either MRI activity or relapse rates.

“There was no increase in radiological or clinical disease activity for personalized [less-frequent dosing] versus [standard-interval dosing],” Toorop concluded.

NfL levels stable

In both groups that got extended-interval dosing of Tysabri, levels of a nerve damage marker called neurofilament light chain (NfL) were stable over the course of the study. No cases of PML were reported in the trial, and there were no differences between the groups in terms of positivity for the virus that causes PML.

Overall these findings indicate that “interval extension to a drug concentration of 5 [mcg]/mL is likely a safe aim to extend [Tysabri] treatment intervals [beyond] 6 weeks,” the researchers concluded in their abstract.

The scientists now are continuing a modified version of the NEXT-MS study called SUPERNEXT, where patients change their dosing of Tysabri to a minimum of every six weeks, and then receive personalized dosing to keep levels at or above 5 mcg/mL.

“We expect around 30% to 40% of participants to be able to extend [dosing intervals] beyond six weeks, thereby further reducing treatment burden, healthcare cost, and, potentially, PML risk,” Toorop said. “Hopefully in the nearby future, personalized treatment will become the new standard for all patients with MS.”

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the 9th joint ECTRIMS-ACTRIMS meeting Oct. 11-13. Go here to see the latest stories from the conference.