Serum Neurofilament Light (sNfL) Levels in Patients with Relapsing-remitting Multiple Sclerosis (RRMS) Switching from Natalizumab Every-4-week (Q4W) Dosing to Extended Interval Dosing (EID) (2013)

Objective: Evaluate sNfL levels in RRMS patients who switched from natalizumab Q4W dosing to EID compared to those who remained on Q4W dosing in a real-world setting.

Background: Natalizumab EID is associated with a lower risk of progressive multifocal leukoencephalopathy compared to Q4W dosing in anti-JC virus (JCV) antibody positive patients. Previous studies indicate no increased clinical or radiological disease activity in patients receiving EID vs Q4W dosing. sNfL is a proposed biomarker of MS disease activity in patients with RRMS.

Design/Methods: RRMS patients stable on natalizumab Q4W dosing for 2.5 years were switched to EID (average dosing interval ≥35 days) or remained on Q4W dosing for ≥6 additional infusions. sNfL levels were measured in samples collected before switch and after reaching presumptive steady-state (≥6 months) post-switch to EID using the Simoa NF-light^® Advantage Kit. sNfL differences on Q4W vs EID were assessed after adjustment for baseline covariates (age, sex, height, weight, and anti–JCV antibody serostatus) using (1) parallel analyses in patients who stayed on Q4W dosing or switched to EID;(2) analyses pre- and post- switch from Q4W to EID, and (3) modeled robust linear regression analyses in patients with complete pre- and post-switch sNfL data additionally adjusted for Q4W sNfL levels.

Results: Sixty patients switched to EID and 79 remained on Q4W dosing. After covariate adjustment, sNfL levels were not significantly different in EID vs Q4W groups using parallel (P=0.60) and pre/post (P=0.10) analyses. Modeled robust regression analysis (complete data set n=99) did not show any statistically significant differences between Q4W and EID (P=0.80).

Conclusions: These results, while limited by small sample size and potential selection bias, indicate that patients in real-world clinical practice who switched from natalizumab Q4W to EID showed no increase in sNfL levels, supporting previous reports that EID is not associated with increased disease activity.

Disclosure: Dr. Foley has nothing to disclose. Dr. Xiong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen.Dr. Hoyt has nothing to disclose. Dr. Singh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of and hold stock and/or stock options in Biogen. Dr. Riddle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of and hold stock and/or stock options in Biogen. Dr. Riddle holds stock and/or stock options in Biogen which sponsored research in which Dr. Riddle was involved as an investigator. Dr. DeMoor has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. DeMoor holds stock and/or stock options in Hold stock/stock options in Biogen which sponsored research in which Dr. DeMoor was involved as an investigator. Dr. Campbell has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Campbell has received compensation for serving on the Board of Directors of Received stock as employee of Biogen. Dr. Campbell holds stock and/or stock options in Biogen. Dr. Plavina has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen at the time of this analysis. Dr. Plavina holds stock and/or stock options in Hold stock/stock options in Biogen which sponsored research in which Dr. Plavina was involved as an investigator.