eprintid: 10135481 rev_number: 20 eprint_status: archive userid: 608 dir: disk0/10/13/54/81 datestamp: 2021-10-04 09:33:38 lastmod: 2022-09-23 09:52:05 status_changed: 2021-10-04 09:40:18 type: article metadata_visibility: show creators_name: Bridel, C creators_name: Leurs, CE creators_name: van Lierop, ZYGJ creators_name: van Kempen, ZLE creators_name: Dekker, I creators_name: Twaalfhoven, HAM creators_name: Moraal, B creators_name: Barkhof, F creators_name: Uitdehaag, BMJ creators_name: Killestein, J creators_name: Teunissen, CE title: Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F82 note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. abstract: OBJECTIVE: The objective of this study was 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 performedon 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 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 (IQR 4.3-6.7, range 3.0-11.0) after natalizumab initiation, mean age at time of natalizumab initiation was 36.9 (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 versus non-progressors. NfL levels at baseline and 1 year after natalizumab initiation did not predict progression at last follow-up. DISCUSSION: In our cohort of natalizumab-treated patients with RRMS, NfL fails to capture or predict progression that occurs largely independently of clinical or radiological 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. date: 2021-11-09 date_type: published publisher: Ovid Technologies (Wolters Kluwer Health) official_url: https://doi.org/10.1212/WNL.0000000000012752 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1887284 doi: 10.1212/wnl.0000000000012752 lyricists_name: Barkhof, Frederik lyricists_id: FBARK32 actors_name: Barkhof, Frederik actors_id: FBARK32 actors_role: owner full_text_status: public publication: Neurology volume: 97 number: 19 pagerange: e1898-e1905 citation: Bridel, C; Leurs, CE; van Lierop, ZYGJ; van Kempen, ZLE; Dekker, I; Twaalfhoven, HAM; Moraal, B; ... Teunissen, CE; + view all <#> Bridel, C; Leurs, CE; van Lierop, ZYGJ; van Kempen, ZLE; Dekker, I; Twaalfhoven, HAM; Moraal, B; Barkhof, F; Uitdehaag, BMJ; Killestein, J; Teunissen, CE; - view fewer <#> (2021) Serum Neurofilament Light Association With Progression in Natalizumab-Treated Patients With Relapsing-Remitting Multiple Sclerosis. Neurology , 97 (19) e1898-e1905. 10.1212/wnl.0000000000012752 <https://doi.org/10.1212/wnl.0000000000012752>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10135481/3/Barkhof_Neurofilament%20Light%20Association%20With%20Progression%20in%20Natalizumab-Treated%20Patients%20With%20Relapsing-Remitting%20Multiple%20Sclerosis_AAM.pdf