Serum neurofilament levels and patient‐reported outcomes in multiple sclerosis

Abstract

Objective Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients. Methods MS patients with serum samples and health‐outcome measurements collected longitudinally between 2011 and 2016 were analyzed. sNfL values were evaluated across age and gender. Data were analyzed using correlation with log‐transformed sNfL values. Results A total of 304 MS patients with a mean age of 32.9 years, average EDSS of 1.6 (SD = 1.5) and baseline sNfL of 8.8 (range 1.23–78.3) pg/mL were studied. Baseline sNFL values increased with age and were higher in females. Baseline sNfL correlated with baseline Multiple Sclerosis Quality of Life physical composite (mean = 49.4 (9.1), P = 0.035) and baseline EDSS (P = 0.002). Other PRO measures at baseline did not show a significant relationship with baseline sNfL. Average of baseline and follow‐up sNfL correlated with MSQoL physical‐role limitations (mean = 48.9 (10.8), P = 0.043) and social‐functioning (mean = 52.3 (7), P = 0.034) at 24‐month follow‐up. We found a trend for numerically higher sNfL levels in nonpersistent patients compared to those who were persistent to treatment (11.13 vs. 8.53 pg/mL, P = 0.093) measured as average of baseline and 24‐month values. Baseline NfL was associated with number of intravenous steroid infusions (mean = 0.2; SD = 3.0, P = 0.013), whereas the average of baseline and 12 months NfL values related to inpatient stays at 12 months (mean = 0.2; SD = 3.0 P = 0.053). Conclusion Serum NfL is a patient‐centric biomarker that correlated with MS patient health‐outcomes and healthcare utilization measures in a real‐world cohort.

Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

“…According to cross-sectional studies, high baseline CSF NfL levels correlate with high baseline EDSS [ 156 , 285 ] and future EDSS progression [ 276 , 288 , 290 ]. Somewhat contradictory to this data are the results of other studies that confirmed the correlation between baseline CSF [ 298 ], serum [ 289 ] and plasma [ 313 ] NfL levels and baseline EDSS but failed to link them to future EDSS and disability progression. Some studies documented a link between baseline serum NfL and baseline EDSS [ 243 , 269 , 289 , 297 , 311 ], while others did not find such a correlation [ 314 , 315 , 316 ].…”

“…Somewhat contradictory to this data are the results of other studies that confirmed the correlation between baseline CSF [ 298 ], serum [ 289 ] and plasma [ 313 ] NfL levels and baseline EDSS but failed to link them to future EDSS and disability progression. Some studies documented a link between baseline serum NfL and baseline EDSS [ 243 , 269 , 289 , 297 , 311 ], while others did not find such a correlation [ 314 , 315 , 316 ]. In contrast, a few investigations could not reveal any association at all between CSF [ 40 , 157 , 266 , 317 ] or blood [ 272 ] NfL levels and EDSS.…”

“…The association between NfL and gender is also controversial; most studies found no relationship between CSF and serum NfL and sex [ 40 , 271 , 287 , 288 ]. On the other hand, a cohort reported higher serum NfL levels in females [ 289 ], while according to other studies, CSF NfL concentrations were more prominent in male patients [ 290 , 291 ].…”

Role of Blood Neurofilaments in the Prognosis of Amyotrophic Lateral Sclerosis: A Meta-Analysis

“…In summary, although there are relatively few studies on the relationship between blood neurofilament levels and the prognosis of ALS, blood neurofilament levels (NfL/pNfH) may be good predictive biomarkers of ALS patients; that is, higher blood neurofilament levels may be linked to faster DPR and higher risk of death in ALS patients. Although neurofilaments are not specific markers of ALS (e.g., neurofilaments are also promising biomarkers for multiple sclerosis, Alzheimer's disease, and Charcot-Marie-Tooth disease) (46)(47)(48), the predictive effect of neurofilaments on the prognosis of ALS patients suggests to some extent that the pathophysiological mechanism of ALS may be related to changes in the function and concentration of neurofilaments. Besides, neurodegenerative diseases are complex, and biomarkers are just one of the tools to help with diagnosis and treatment.…”

Calprotectin in Chronic Inflammatory Demyelinating Polyneuropathy and Variants—A Potential Novel Biomarker of Disease Activity

“…There is evidence that patients with more severe motor disability, short disease duration, and fatigue have a higher risk of worse quality of life (45). Thus, the relationship between PRO and blood biomarkers like CLP and sNfl should be investigated in larger, independent cohorts, since in other autoimmune diseases like IBD or multiple sclerosis, CLP and sNfl were shown to be a good predictor of health outcomes (46)(47)(48).…”