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ECTRIMS 2021 | Elevated sNfL associated with brain atrophy and new T2 lesions

Elias Sotirchos, MD, Johns Hopkins University School of Medicine, Baltimore, MD, shares the details of a large cohort study examining associations of serum neurofilament light chain (sNfL) with longitudinal brain atrophy and new T2 lesions in patients with multiple sclerosis (MS). The analysis used data from The Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network, an international network of healthcare centers collecting standardized clinical/imaging data during routine clinic visits. Approximately 3700 patients with brain MRI acquisitions within 1 year of sNfL measurement and retrospective and/or prospective MRI follow-up were identified as eligible. The study showed that elevated sNfL was associated with accelerated whole brain atrophy in both the periods before and after NfL measurement. Patients with higher sNfL also had higher odds of new T2 lesions during retrospective and prospective MRI follow-up. Findings were consistent across major demographic and clinical subgroups. This interview took place at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress 2021.

Transcript (edited for clarity)

In this study, we leveraged participants in the Multiple Sclerosis Partners Advancing Technology in Health Solutions network, which is a large real world, well-characterized prospective cohort from 10 MS centers in the United States and Europe.

We aimed to assess the association of neurofilament light chain with longitudinal brain atrophy and new lesion development. Now in MS, there is evidence already that serum neurofilament light chain levels are associated with measures of inflammatory disease activity, and are predictive of brain, as well as spinal cord, atrophy...

In this study, we leveraged participants in the Multiple Sclerosis Partners Advancing Technology in Health Solutions network, which is a large real world, well-characterized prospective cohort from 10 MS centers in the United States and Europe.

We aimed to assess the association of neurofilament light chain with longitudinal brain atrophy and new lesion development. Now in MS, there is evidence already that serum neurofilament light chain levels are associated with measures of inflammatory disease activity, and are predictive of brain, as well as spinal cord, atrophy. However, existing data are mainly derived from single center studies, or post-hoc analyses of clinical trial cohorts that are largely homogeneous. We sought to evaluate this in a larger population that is more diverse and heterogeneous in the MS PATHS cohort, in a larger real world cohort.

We looked at neurofilament light chain and its ability both… So the participants had measurements performed at a single time point, and that time point was linked to an index MRI. And then what we did was, we looked back, so we looked retrospectively, to see, compared to a prior available MRI, the change in brain volume, as well as prospectively, so looking at subsequent MRIs, what was the association between the NfL at the time of that index MRI and future brain atrophy and new T2 lesion development?

We were able to include in this analysis, approximately 3,700 participants who were eligible for inclusion, in either of the retrospective, or prospective analysis, of whom about 17% had elevated NfL. And what we found was that, NfL was associated with a faster rate of brain atrophy, both in the period preceding the measurement of NfL, as well as this period after that, with an approximately two-fold difference in the rate of brain atrophy between those who were classified as having elevated NfL, based on measurements in the healthy control cohort that we had, versus normal levels of NfL. And this was about the same in both the prospective and retrospective analysis, about a two-fold difference in the rates of brain atrophy.

These findings were fairly consistent across key demographic subgroups, and across MS subtypes. We’re looking at across relapsing-remitting versus progressive MS. And then, we also assessed similarly the association between new T2 lesions, again, either in the preceding period, or the following period after the measurement of NfL, and saw that elevated NfL, above the cut-off that we have been using for health controls, was associated with about a 2.7 fold increase in the odds of a new T2 lesion in the preceding period, and an almost two-fold increase in the odds of a new T2 lesion in the following period, after the NfL measurement. Also, with similar findings across the key demographic and clinical subgroups.

This study supports that, first of all, our study included a single baseline measurement. And so, this supports that a single measurement can be associated with short-term retrospective and prospective brain atrophy, and new T2 lesion development.

Now, this was a relatively short follow-up duration, with the median retrospective follow-up being one year and the median prospective follow-up being 1.7 years. Importantly, these associations were overall consistent across disease subtypes and demographic groups. And it supports the rationale for further studies to evaluate the use of NfL potentially, in clinical practice. And I do think that it will be important to assess the utility of serial monitoring, rather than a single time point, since it is likely that it will allow us to get a better overall picture of the disease course. And this is an analysis that we are pursuing in the MS PATHS network. So looking at serial NfL measurement, and associations with both longer-term radiological outcomes, as well as with clinical outcomes.

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Disclosures

Dr. Sotirchos has served on scientific advisory boards for Alexion, Viela Bio and Genentech, and has received speaker honoraria from Viela Bio and Biogen.