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," Simon Thebault, MBBCh, University of Ottawa and the Ottawa Hospital Research Institute, Canada, told Medscape Medical News.
This research is being presented on AAN.com 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, Thebault explained.
The new study took advantage of the Ottawa MS biobank, which contains carefully frozen and stored samples from more than 3000 MS patients 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 MS patients, the median baseline sNfL level was 10.1 pg/mL — 38.5% higher than the median level in controls (7.26 pg/mL, P = .004).
The baseline sNfL level was "most helpful as a sensitive predictive marker to rule out disease progression," the researchers report 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 = .001) and 7.1 times less likely to develop progressive MS by end of follow-up (P = .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," Thebault told Medscape Medical News. 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," 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.
Noteworthy Study
Commenting on the study for Medscape Medical News, Asaff Harel, MD, neurologist at Lenox Hill Hospital in New York City, said the findings in this study are "noteworthy, as there is a relative lack of effective prognostic biomarkers in the field of MS."
"It remains to be seen whether this improves risk stratification of patients above what can be achieved by looking at other prognostic factors, such as age, gender, baseline EDSS, and severity and frequency of relapses during early disease course," Harel cautioned.
"This was a relatively small study and further research is necessary," Harel added. It's also worth noting, he said, that out of the 67 patients who met criteria to be included in the study (ie, those with blood samples taken during "early MS," more than 15 years ago), almost half were lost to follow-up, which could potentially open the study to error.
It's also "unclear whether early NfL level is a better prognostic marker than severity of early disease course and baseline EDSS, both of which were not addressed in the study, and this will be interesting to determine in the future," Harel commented.
Funding for the study was provided by The Ottawa Hospital Pilot Project Grant. Thebault and Harel have disclosed no relevant financial relationships.
American Academy of Neurology (AAN) 2020 Annual Meeting: Abstract S10.008
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Cite this: Serum NfL in Early MS Can Help PredictClinical Course - Medscape - May 06, 2020.
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