Review Study Highlights Potential of NfL as MS Prognosis Biomarker
NfL levels associated with increased risk of confirmed disability worsening
Levels of neurofilament light chain (NfL), a biomarker of nerve cell damage, may help predict multiple sclerosis (MS) prognosis and response to treatment with Gilenya (fingolimod), according to a review of five randomized clinical trials.
Most of the evaluations in the review study were qualitative, however, meaning trial results were described, but statistical analyses weren’t always done to reveal relationships across studies.
Although larger and longer studies are still needed, the findings serve “as an adjunct to positively debate the potential role of NfL in the treatment of MS,” the researchers wrote, noting they add to an increasingly large body of evidence suggesting NfL measurements can help diagnose MS, predict its course, and determine treatment responses.
The study, “Prognostic significance of neurofilament light in Fingolimod therapy for Multiple Sclerosis: A systemic review and meta-analysis based on randomized control trials,” was published in Multiple Sclerosis and Related Disorders.
NfL is a protein released from nerve cells when they’re damaged. Thus, elevations in NfL levels in the blood or cerebrospinal fluid (CSF) — the fluid surrounding the brain and spinal cord — are recognized as an indicator of nerve cell damage in neurodegenerative diseases like MS.
A growing number of studies have shown NfL levels are elevated in the blood of MS patients years before a diagnosis. Higher levels of the protein have been associated with a faster disease progression.
Researchers have begun using NfL to monitor how effective a treatment is during clinical trials. If NfL levels are lowered with a given treatment, it’s considered a sign the therapy is effectively protecting nerve cells from damage.
They reviewed published data from five randomized clinical trials of Gilenya that collected NfL data from either the blood or CSF. These included the FREEDOMS (NCT00289978) and TRANSFORMS (NCT00340834) Phase 3 clinical trials, which supported Gilenya’s approvals.
The five trials involved 5,025 participants, with an average age of 38. Study length ranged from one to three years.
Across four studies for which a meta-analysis — a type of statistical analysis combining data from multiple studies — could be conducted, the researchers found higher NfL levels were associated with a significantly increased risk of confirmed disability worsening.
The relationship between NfL levels and other clinical parameters was evaluated in a qualitative, or non-statistical, manner. In general, the trials’ findings indicated early NfL levels tended to be higher in patients having more MS relapses and who developed more brain lesions, and in patients and greater brain shrinkage.
“All these reported conclusions highlight the significance of NfL as a potential biomarker and a surrogate to MRI in determining disease progression in MS,” the researchers wrote.
A qualitative analysis also found NfL levels were significantly lowered with Gilenya treatment versus a placebo in each of the five clinical trials, suggesting it “can be used as a therapeutic agent to lower the level of NfL prognostic marker in MS,” the team wrote, noting new and longer trials should be done to obtain a better understanding and strengthen their finding.