Measuring the blood level of neurofilament light chain (NfL) may predict brain shrinkage in primary progressive (PPMS) and secondary progressive multiple sclerosis (SPMS), according to a new study. The findings also show that NfL levels are associated with brain lesion load in these patients.
The research, “Neurofilament light levels in the blood of patients with secondary progressive MS are higher than in primary progressive MS and may predict brain atrophy in both MS subtypes,” was presented by Ludwig Kappos, MD, from the University Hospital Basel, Switzerland, on Oct. 12 at the 34th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in Berlin, Germany.
According to Kappos, “neurofilament light chain (NfL) is specific to neurons and reflects damage to the brain and spinal cord.”
Increasing research has indicated that NfL can be a blood biomarker of disease activity, damaged neurons, and treatment response in MS patients. However, as most studies have addressed relapsing-remitting MS (RRMS), information on blood NfL levels in patients with progressive MS is still scarce.
Aiming to address this gap, the study — funded by Novartis — compared blood NfL baseline levels and assessed the potential of NfL to predict brain atrophy (shrinkage) in patients with PPMS and SPMS enrolled in the Phase 3 trials evaluating Gilenya (fingolimod) in PPMS patients (INFORMS trial, NCT00731692), and of the investigational compound siponimod in SPMS (EXPAND trial, NCT01665144).
A total of 1,452 SPMS patients (mean age 48.2 years, and mean Expanded Disability Status Scale (EDSS) score of 5.4, which corresponds to disability severe enough to impair full daily activities) and 378 PPMS patients (mean age 48.7 years and mean EDSS score of 4.6, which means significant disability but capacity to work a full day) were analyzed.
Mean baseline NfL levels were grouped into three categories: low (under 30 pg/mL), medium (30-60 pg/mL), and high (above 60 pg/mL). The team evaluated the association between baseline NfL levels with magnetic resonance imaging (MRI) measures regarding lesion count, lesion volume, and brain volume change.
Results showed that mean baseline NfL levels were higher in SPMS patients than in PPMS (32.1 versus 22.0 pg/mL), also when comparing patients of the same age. SPMS patients’ higher baseline NfL levels also were observed in the presence of MRI lesions (45.0 versus 34.0 pg/mL in PPMS) and in the absence of lesions (29.2 versus 21.0 in PPMS).
The lesion count and lesion volume was found to correlate with baseline NfL levels.
“In both SPMS and PPMS, higher NfL levels were associated with older age and higher disease activity (increased EDSS score, more lesions and higher lesion load),” Kappos said in the presentation.
The data also showed that, in both SPMS and PPMS patients, high NfL levels at baseline were associated with a higher percentage of brain shrinkage at month 12. High NfL levels were associated with a 0.8% shrinkage of the brain, while low NfL levels were associated with a 0.2% shrinkage in SPMS, and a 0.8% and 0.4% shrinkage, respectively, in PPMS patients.
At month 24, brain shrinkage was of 1.5% and 0.5% in SPMS patients with high or low NfL, respectively; and of 1.9% and 0.8% in PPMS patients.
Kappos also reported that the risk of disability progression in patients with NfL levels equal or higher than 30 pg/mL was “increased by 32%” in SPMS patients, and by 49% in PPMS patients.
The researchers also observed that “NfL levels were reduced by active treatment,” Kappos said, referring to Gilenya and siponimod.
Overall, the team concluded that “NfL levels are higher in SPMS than in PPMS patients, independent of age” Kappos said, and that in both patient groups, “NfL at baseline predicts future brain atrophy and … confirmed disability worsening.”
The results also suggest that SPMS patients have more ongoing loss of neurons than PPMS patients, with or without MRI lesions.
Taken together, “in both SPMS and PPMS patients, NfL may serve as a prognostic marker of brain atrophy,” the team wrote. Kappos also suggested that “NfL should be considered as an informative endpoint for Phase 2 studies in SPMS.”
Of note, five of the study’s authors are Novartis’ employees, while another author received travel support from the same company. Also, University Hospital Basel, the institution where two other authors work, received speaker fees, consulting fees, travel expenses and research funding from Novartis.