Aubagio Significantly Lowers Plasma NfL Levels in TERIKIDS Trial

Aubagio (teriflunomide) can significantly reduce plasma neurofilament light chain (pNfL) levels, a biomarker of nerve cell damage, in children and adolescents with relapsing-remitting multiple sclerosis (RRMS).

That’s according to a new analysis of data from TERIKIDS (NCT02201108), the Phase 3 trial that supported expanding Aubagio’s indication in Europe to include young patients, ages 10–17.

In the trial, plasma NfL at the start of treatment was significantly associated with a higher risk of high lesion load or relapses, but the researchers said further research was needed to confirm its use “as a biomarker for monitoring disease activity and treatment effects in clinical practice.”

Their findings were published in the Multiple Sclerosis Journal in the study, “Plasma neurofilament light chain in children with relapsing MS receiving teriflunomide or placebo: A post hoc analysis of the randomized TERIKIDS trial.”

Sanofi’s Aubagio is a daily tablet approved for relapsing forms of MS. Its use is restricted to adults in the U.S., but the medication has been expanded to include children and adolescents (ages 10 and up) in the European Union.

Exactly how Aubagio works in MS is unclear, but it’s thought to reduce the number of lymphocytes, a type of immune cell that plays a part in the damaging inflammation that contributes to the disease.

NfL is a protein that supports nerve cells and is released to the spinal fluid and blood when they are damaged. This is often used as a biomarker of nerve cell damage that helps physicians monitor disease progression and response to treatment in MS and other neurodegenerative diseases.

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Testing plasma NfL as biomarker in children, teens

To see if pNFL can be used as a biomarker in children and adolescents and help monitor Aubagio response, researchers at Sanofi and colleagues examined data from the 111 patients in TERIKIDS who provided NfL measurements throughout the trial. This group made up 67% of its total participants.

Of them, 78 were assigned Aubagio and 33 were given a placebo for up to 96 weeks. All of them received Aubagio for up to an additional 96 weeks during the trial’s open-label extension.

At the start of TERIKIDS (baseline), plasma NfL levels were similar in the Aubagio and placebo groups (19.83 vs. 18.30 picograms per milliliter, or pg/mL). In both, higher plasma NfL was significantly associated with a shorter disease duration, more inflammatory lesions, and greater total lesion volume.

NfL levels decreased more among patients on Aubagio. The largest difference between the groups was observed at week 24, when the level of plasma NfL in the Aubagio group was about 25% lower than the placebo group. This difference disappeared when the researchers took into account the number of lesions on MRI scans, however.

In the open-label extension, NfL levels continued to reduce for those who’d started the trial on Aubagio. Those who transitioned from a placebo also saw their NfL levels decrease, but they were always higher than the group who’d been on Aubagio the entire time.

By the end of the open-label extension, plasma NfL was significantly lower in the Aubagio group than the placebo group (10.61 vs. 17.32  pg/mL).

A final set of analyses to determine the prognostic value of NfL showed the baseline levels of this marker were significantly associated with a higher risk of high MRI activity or of having a relapse during the randomized part of the trial.

For each doubling of plasma NfL levels at baseline, patients had a 22% higher risk of these clinical signs of MS. The findings suggest plasma NfL could be “a useful biomarker of the risk of acute focal inflammatory activity in pediatric MS,” the researchers said.