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Serum NfL in early MS can help predict clinical course


The serum level of neurofilament light chain (sNfL) around the time of multiple sclerosis (MS) diagnosis is associated with long-term clinical disease progression, with higher baseline levels a sensitive marker of subsequent poor clinical outcomes, research suggests. The study showed that patients with higher sNfL within 5 years of MS diagnosis had a higher risk of long term-clinical disability and higher risk of developing progressive MS. The level of sNfL also predicted the rate of increase over time in the Expanded Disability Status Scale (EDSS).

Serum NfL levels can provide “useful information in both directions, adding to both an overall reassuring picture or worrying picture both at first presentation and then on subsequent visits,” said Simon Thebault, MBBCh, a neurology resident at the University of Ottawa and the Ottawa Hospital Research Institute, Canada.

This research was presented online as part of the 2020 American Academy of Neurology Science Highlights.

Prognostication from day one

Many studies have shown a correlation between MS disease activity (clinical relapses, EDSS progression, MRI lesions) and elevated sNfL. Other studies have also looked at the prognostic value of NfL in serum and cerebrospinal fluid (CSF), but the data are limited by the lack of long-term biobanked samples and subsequent follow-up, Dr. Thebault explained.

The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3,000 patients with MS going back up to 25 years.

The team identified patients with serum collected within 5 years of first MS symptom onset (baseline) who were followed for a median of 18.9 years (range 15.0 to 27.0 years). They quantified levels of sNfL in 67 patients and 37 matched controls.

In patients with MS, the median baseline sNfL level was 10.1 pg/mL – 38.5% higher than the median level in controls (7.26 pg/mL, P = 0.004).

The baseline sNfL level was “most helpful as a sensitive predictive marker to rule out disease progression,” the researchers reported in their meeting abstract.

Patients with baseline sNfL levels less than 7.62 pg/mL were 4.3 times less likely to develop significant disability (EDSS score ≥ 4; P = 0.001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = 0.054).

The most rapid disease progression was seen in patients with the highest baseline NfL levels (3rd-tertile, > 13.2 pg/mL). Higher baseline sNfL level was associated with faster rate of EDSS progression even after adjusting for confounders of age, sex, and disease-modifying treatment.

“We were able to show that serum neurofilament levels collected very early in the disease, usually at the time of first diagnosis, were predictive of the clinical progression [by EDSS score] and the risk of evolving to secondary progressive MS on average 19 years later,” Dr. Thebault said. A baseline level less than 7.6 pg/mL was “reassuring.”

“Prognostication in MS from day one is important,” he emphasized.

“If we know someone is on a bad trajectory, neurologists might recommend more aggressive therapies up front. Equally, if a patient has a very reassuring picture, then maybe it is more appropriate to start with safer treatments [the so called ‘platform therapies’] that may serve a patient well for many years, as they did for many in the years before higher-efficacy therapies were available,” Dr. Thebault said.

“In the hands of an expert MS neurologist who understands both the pearls and pitfalls of this test ... serum neurofilament is already a useful clinical tool, and we have implemented it in our daily practice in Ottawa,” he concluded.

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