NfL blood levels predict CIS to MS conversion: Clinical trial data

High blood levels of the nerve damage biomarker neurofilament light chain (NfL) significantly increased the risk of people with clinically isolated syndrome (CIS) converting to definite multiple sclerosis (MS), according to an analysis of clinical trial data.

CIS patients with higher NfL levels also made the transition earlier than those with lower levels of the biomarker, indicating it may be used as a prognostic factor in these patients. However, receiving treatment early after a first clinical event significantly lowered the risk of transition.

The study, “Serum neurofilament light chain correlations in patients with a first clinical demyelinating event in the REFLEX study: a post hoc analysis,” was published in the journal Therapeutic Advances in Neurological Disorders.

MS is caused by an abnormal inflammatory response that leads to progressive neuronal damage in the brain and spinal cord. The damage can be seen as lesions on MRI scans.

A first episode of MS-like symptoms generally is considered CIS, which can be thought of as a single relapse of MS. Some people with CIS will never experience additional symptoms or develop new lesions, but others may experience another relapse and/or develop new lesions, and thus be diagnosed with MS.

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Brain lesions associated with MS

The likelihood of CIS becoming overt MS is known to be associated with the presence or absence of brain lesions. People without detectable brain lesions at the time of their CIS diagnosis have about a 20% chance of progressing to MS, according to the National MS Society, while those with brain lesions have a 60% to 80% chance of MS.

NfL is a protein that helps to give structure and support to nerve fibers. However, when nerve fibers are damaged, this protein gets releases into bodily fluids, making it a useful biomarker of nerve damage and treatment response in MS.

Studies have shown that NfL levels are elevated in MS patients years before the onset of symptoms and are a good prognostic factor for disease course and future disability levels in people with the condition.

A team led by scientists at the University Hospital and University of Basel in Switzerland set out to determine whether serum NfL (sNFL) levels can also predict the conversion from CIS to MS.

The team tested NfL levels in blood samples collected from individuals who participated in the two-year REFLEX Phase 3 study (NCT00404352), which evaluated the approved therapy Rebif (interferon beta-1a) in 517 people with early signs of MS who had yet to receive a definite MS diagnosis.

Overall, two years of Rebif treatment significantly reduced the risk of converting to full MS by about 50% compared with a placebo.

The trial and the recent analyses were both funded by Merck KGaA, the company that markets Rebif and is known as EMD Serono in the U.S. and Canada.

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Time to conversion longer for those with low sNfl levels

The NfL analysis involved 494 participants, of whom 318 were women. The median NfL level in these patients was 26.1 picograms/mL, and this was used as a cut-off value to create two groups of patients with high and low NfL levels.

Analysis revealed that patients with high baseline sNfL levels, or those above the cut-off value, were 30% more likely to convert to MS under the 2005 McDonald Criteria, which were established guidelines for correctly identifying MS.

Other factors that were significantly associated with conversion were older age; multifocal CIS classification, which refers to multiple symptoms caused by lesions in more than one area; and the number of lesions, either total lesions or lesions with active inflammation. In turn, receiving Rebif was significantly associated with a lower risk of conversion, as has been shown in the trial.

Consistently, the median time to MS conversion was significantly longer among the low sNfL group than in the high sNfL group, and was also longer among those who received treatment versus a placebo in both groups.

“Higher baseline sNfL was associated with an increased risk of MS conversion, a risk that was mitigated by treatment with [Rebif, three times weekly],” the researchers wrote. “These exploratory findings highlight the complex interplay between sNfL concentration, MRI outcomes, and risk of conversion to MS in patients with a [CIS].”