Elevated Plasma NfL Levels Linked to Worse Disability in Multiple Sclerosis

Author(s):

Plasma neurofilament light chain (pNfL) may serve as a prognostic tool to assess the risk of developing permanent disability in multiple sclerosis.

Ali Manouchehrinia, PhD

Results from a study revealed that elevated plasma neurofilament light chain (pNfL) levels at the early stages of multiple sclerosis (MS) are associated with an increased risk of reaching sustained disability worsening.

High pNfL levels were associated with increased adjusted rates of Expanded Disability Status Scale (EDSS) scores of 3.0, with adjusted rates ranging between 1.5 (95% CI, 1.2—1.8) and 1.55 (95% CI, 1.3–1.8) over all percentile cutoffs (all P <.001). Additionally, increased adjusted rates of EDSS scores worsening between ranges of 1.4 (95% CI, 1.1—1.8) and 1.7 (95% CI, 1.3–1.8) were directly associated with high levels of pNfL.

Ali Manouchehrinia, PhD, first author, assistant professor of clinical neuroscience, Institute of Karolinksa, and colleagues noted that there was a similar increase for the risk of sustained EDSS score of 4.0 but did not find any consistently significant association between reaching sustained EDSS score 6.0 and conversion to secondary progressive MS (SPMS).

The median duration of follow-up was 5 years (interquartile range [IQR], 5.1 years). A total of 3370 patients were included in the analysis of risk of reaching sustained EDSS score 3.0, and 525 (15.5%) reached this outcome. Additionally, 352 (9.1%) of the 3840 patients and 199 (5.0%) of the 3990 patients included in the analyses of risk of reaching sustained EDSS scores 4.0 and 6.0, reached these milestones, respectively.

Conversion to SPMS during the follow-up time occurred in 279 (7.3%) of the 3824 relapsing-onset patients. Notably, there was no significant increase in the risk of conversion to SPMS when models were adjusted for the baseline EDSS score or body mass index (BMI).

Among the control population, there was a significant association between the pNfL levels and age at the time of sampling where the pNfL level increased by 0.18 pg/mL (95% CI, 0.17—0.20; P <.001) per year of age.

The study population included a subset of 4385 persons with MS and 1026 randomly selected, population-based, sex- and age-matched cohorts using the highly sensitive Single Molecule Array (SimoaTM) NF-Light Advantage Kit. Data such as patient characteristics, disease modifying treatment (DMT) exposure, visits, clinical scales, relapses, magnetic resonance imaging (MRI), and laboratory tests were all recorded by neurologists or MS nurses through a web interface.

EDSS score milestones 3.0 (moderate disability), 4.0 (significant disability but able to walk without aid or rest for 500 m), and 6.0 (requirement of unilateral assistance to walk about 100 m with or without resting) were the end points of the study. Patients who met end point at baseline were excluded from the study. Manouchehrinia and colleagues used survival analysis from the date of sampling to determine the risk of conversion to SPMS in patients with relapsing-onset MS.

Patients with MS were categorized according to the age-stratified pNfL levels above and below the 80^th (C80), 95^th (C95), and 99^th (C99) percentiles among controls. Researchers used Cox proportional hazard regression models while adjusting for potential confounders to calculate the risk of reaching the outcomes from the date of sampling, and ultimately analyzing the risk of reaching EDSS milestones or SPMS.

“In conclusion, elevated pNfL levels measured early on in the disease course are associated with an increased risk of reaching sustained disability milestones. Hence, pNfL may serve as a prognostic and treatment monitoring tool to assess the risk of developing permanent disability in MS as part of a more standardized, noninvasive, longitudinally accessable, and generalized approach,” Manouchehrinia and colleagues wrote.

REFERENCE

Manouchehrinia A, Stridh P, Khademi M, et al. Plasma neurofilament light levels are associated with the risk of disability in multiple sclerosis. Neurology. 2020;94:e2457-e2467. doi: 10.1212/WNL.0000000000009571.