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Neurofilament light chain predicts disease activity in relapsing-remitting MS
Kristin N Varhaug1, Christian Barro1, Kjetil Bjørnevik1
1Department of Neurology (K.N.V., K.B., K.-M.M., Ø.T., S.W., L.A.B., C.V.), Haukeland University Hospital; Department of Clinical Medicine (K.N.V., K.-M.M., Ø.T., S.W., L.A.B., C.V.), University of Bergen, Norway; Neurologic Clinic and Policlinic (C.B., J.K.), Departments of Medicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Global Public Health and Primary Care (K.B.), University of Bergen, Norway; and Norwegian MS-Registry & Biobank (K.-M.M.).
Objective:
To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS).
Methods:
A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24. Serum samples were collected at baseline and months 3, 6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array assay and CHI3L1 by ELISA and estimated the association with clinical and MRI disease activity using mixed-effects models.
Results:
NF-L levels were significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3 pg/mL, interquartile range [IQR] 25.9-52.4) and new T2 lesions (37.3 pg/mL, IQR 25.1-48.5) compared with those without (28.0 pg/mL, IQR 21.9-36.4, β = 1.258, p < 0.001 and 27.7 pg/mL, IQR 21.8-35.1, β = 1.251, p < 0.001, respectively). NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment.
Conclusion:
Serum NF-L could be a promising biomarker for subclinical MRI activity and treatment response in RRMS. In clinically stable patients, serum NF-L may offer an alternative to MRI monitoring for subclinical disease activity.
Clinicaltrialsgov Identifier:
NCT00360906.
