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Abstract
Background and Objectives To investigate the potential of serum neurofilament light (NfL) to reflect or predict progression mostly independent of acute inflammatory disease activity in patients with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab.
Methods Patients were selected from a prospective observational cohort study initiated in 2006 at the VU University Medical Center Amsterdam, the Netherlands, including patients with RRMS treated with natalizumab. Selection criteria included an age of 18 years or older and a minimum follow-up of 3 years from natalizumab initiation. Clinical and MRI assessments were performed on a yearly basis, and serum NfL was measured at 5 time points during the follow-up, including on the day of natalizumab initiation (baseline), 3 months, 1 year, and 2 years after natalizumab initiation, and on last follow-up visit. Using general linear regression models, we compared the longitudinal dynamics of NfL between patients with and without confirmed Expanded Disability Status Scale (EDSS) progression between year 1 visit and last follow-up, and between individuals with and without EDSS+ progression, a composite endpoint including the EDSS, 9-hole peg test, and timed 25-foot walk.
Results Eighty-nine natalizumab-treated patients with RRMS were included. Median follow-up time was 5.2 years (interquartile range [IQR] 4.3–6.7, range 3.0–11.0) after natalizumab initiation, mean age at time of natalizumab initiation was 36.9 years (SD 8.5), and median disease duration was 7.4 years (IQR 3.8–12.1). Between year 1 and the last follow-up, 28/89 (31.5%) individuals showed confirmed EDSS progression. Data for the EDSS+ endpoint was available for 73 out of the 89 patients and 35/73 (47.9%) showed confirmed EDSS+ progression. We observed a significant reduction in NfL levels 3 months after natalizumab initiation, which reached its nadir of close to 50% of baseline levels 1 year after treatment initiation. We found no difference in the longitudinal dynamics of NfL in progressors vs nonprogressors. NfL levels at baseline and 1 year after natalizumab initiation did not predict progression at last follow-up.
Conclusion In our cohort of natalizumab-treated patients with RRMS, NfL fails to capture or predict progression that occurs largely independently of clinical or radiologic signs of acute focal inflammatory disease activity. Additional biomarkers may thus be needed to monitor progression in these patients.
Classification of Evidence This study provides Class II evidence that serum NfL levels are not associated with disease progression in natalizumab-treated patients with RRMS.
Glossary
- 9HT=
- 9-hole peg test;
- DMT=
- disease-modifying therapy;
- E+NP=
- EDSS+ nonprogressors;
- E+P=
- EDSS+ progressors;
- EDSS=
- Expanded Disability Status Scale;
- EDSS+=
- a composite endpoint including the Expanded Disability Status Scale, the 9-hole peg test, and the timed 25-foot walk test;
- ENP=
- EDSS nonprogressors;
- EP=
- EDSS progressors;
- GE=
- gadolinium-enhancing;
- IQR=
- interquartile range;
- MS=
- multiple sclerosis;
- NfL=
- neurofilament light;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SPMS=
- secondary progressive multiple sclerosis;
- T25W=
- timed 25-foot walk test
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Class of Evidence: NPub.org/coe
CME Course: NPub.org/cmelist
Editorial, page 887
- Received December 16, 2020.
- Accepted in final form July 26, 2021.
- © 2021 American Academy of Neurology
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- Author Response: Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis
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