#ECTRIMS2018 – Plasma Neurofilament Light Levels Linked to Treatment Effects in RRMS, Study Finds

Levels of proposed biomarker neurofilament light chain (NfL) are associated with therapeutic effects of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (RRMS) patients, according to a real-world study.

Study findings also revealed that treatment with either Lemtrada (alemtuzumab, marketed by Sanofi Genzyme), Gilenya (fingolimod, marketed by Novartis), Tecfidera (dimethyl fumarate, marketed by Biogen), or Tysabri (natalizumab, marketed by Biogen) reduced NfL levels to a greater extent than Aubagio (teriflunomide, marketed by Sanofi Genzyme).

The research, “Plasma neurofilament light levels segregate treatment effects: results from the IMSE studies with multiple disease modulatory drugs,” was presented at the 34^th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), which took place Oct. 10-12 in Berlin.

Fredrik Piehl, MD, PhD, from the Karolinska Institutet in Sweden, presented the data.

Recent evidence has shown that plasma levels of NfL are associated with disease activity in RRMS patients, and are reduced in those starting a DMT. However, comparisons among multiple DMTs in real-world populations are still lacking.

Aiming to address this, the study — funded by Novartis, Sanofi Genzyme, and Biogen — measured NfL in plasma samples from patients starting DMT treatment in the Swedish observational Immunomodulation and Multiple Sclerosis Epidemiology (IMSE) study.

The samples were collected at the start of treatment and at roughly one year (between nine and 15 months) into DMT treatment from RRMS patients, of whom 152 were on Aubagio, 278 on Gilenya, 339 on Tecfidera, 287 on Tysabri, and 89 on Lemtrada. A total of 1,026 controls were used to calculate age-adjusted NfL values.

NfL levels were determined using the Single Molecule Array (Simoa) NF-light Advantage kit. 

Results showed that patients starting Tysabri were younger, and had higher baseline (initial) NfL values, a higher number of relapses over the prior year, and higher Expanded Disability Status Scale scores (meaning worsened disability) than those starting Aubagio.

Results of patients starting Gilenya or Tecfidera were in between those of the Tysabri and Aubagio treatments.

Age-adjusted initial NfL values correlated with the number of previous relapses. One-year changes in NfL values were influenced by baseline NfL numbers (causing 20% of the variance), type of DMT (20% variance), and age (4% variance).

According to the team, the link between prior relapses, baseline NfL values, and NfL levels at one year suggests “a slow degree of normalization or lingering disease activity at 12 months.”

Data also showed that, after adjustment for baseline levels, compared with Aubagio, a more marked reduction in NfL levels upon treatment was seen with Lemtrada, followed by Tysabri, Gilenya, and Tecfidera — no significant differences were found among these three.

“These findings support the notion of using NfL for monitoring treatment effects in RRMS,” the team wrote.

Of note, two of the study’s authors are employees of Biogen, one is an employee of Novartis, and another is employee of Sanofi Genzyme. Other authors received various types of support, including research funding, speaker fees, consultancy fees and travel support from Biogen, Novartis, Sanofi Genzyme, and/or Roche (which owns Genentech).