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An integral measure of serial neurofilament light chain assessments in blood is a predictor of long-term disability progression in relapsing-remitting multiple sclerosis
Author(s): ,
J. Kuhle
Affiliations:
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland
,
J. Cohen
Affiliations:
Neurological Institute, Cleveland Clinic, Cleveland, OH, United States
,
D.A. Häring
Affiliations:
Novartis Pharma AG, Basel, Switzerland
,
H. Kropshofer
Affiliations:
Novartis Pharma AG, Basel, Switzerland
,
D. Leppert
Affiliations:
Novartis Pharma AG, Basel, Switzerland
,
D. Tomic
Affiliations:
Novartis Pharma AG, Basel, Switzerland
L. Kappos
Affiliations:
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland
ECTRIMS Online Library. Kuhle J. Oct 12, 2018; 229067; P1227
Jens Kuhle
Jens Kuhle
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Abstract: P1227

Type: Poster Sessions

Abstract Category: Therapy - Long-term treatment monitoring

Background: Neurofilament light (NfL) chain is a cytoskeletal protein that is released into the cerebrospinal fluid and eventually in blood following neuroaxonal injury. In relapsing-remitting multiple sclerosis (RRMS), single measurements of elevated NfL concentrations (e.g. at baseline) are correlated with disease activity and are predictive of mid-term lesions and brain atrophy. We hypothesise that an integral measure of several NfL assessments over time may predict long-term disability outcomes in RRMS.
Objective: To assess the predictive value of serial NfL assessments collected over 1 or 2 years in reaching time to 6-month confirmed disability progression (6mCDP) and time to Expanded Disability Status Scale score of 4 or more (EDSS≥4).
Methods: This post hoc analysis included data from the Phase 3 FREEDOMS trial in patients with RRMS who were randomised to fingolimod 0.5 mg, and continued on the same dose when transitioned into the LONGTERMS extension. The NfL assessments were collected at baseline, and Months 6, 12, 18 and 24 in a subset of patients (N=146). The predictive value of NfL was analysed using a log-rank test and a Cox proportional hazards model with adjustments for sex, age, baseline EDSS, number of relapses in the 2 years prior to study, and quartiles of the geometric mean NfL over 1 or 2 years. The response variable was 6mCDP or time to EDSS≥4 starting after 1 or 2 years. Results are provided with a global log-rank test across all NfL categories, and with a hazard ratio (HR; 95% confidence interval) between the lowest and highest NfL category.
Results: Patients with the highest quartile of NfL were twice as likely to have a 6mCDP compared to the lowest quartile when using the geometric mean NfL over 1 year (log-rank test, p=0.0712; Cox: HR=2.0 [0.81; 5.00], p=0.133) and 2.3-times as likely when using the mean NfL over 2 years (p=0.0221; Cox: HR=2.3 [0.77; 6.81], p=0.137). Patients with the highest quartile of NfL were 3.69-times as likely to reach EDSS≥4 compared to the lowest quartile when using the mean NfL over 1 year (p=0.0034; Cox: HR=2.0 [1.31; 10.4], p=0.014) and 8.7-times as likely when using the mean NfL over 2 years (p=0.0007; Cox: HR=2.3 [2.31; 32.6], p=0.0014).
Conclusion: NfL in blood fulfils a critical requirement as a prognostic biomarker in MS. It predicts long-term physical disability progression in patients with RRMS when taking the mean of several NfL assessments within a period of at least 12 months.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Jens Kuhle´s institution (University Hospital Basel) received the following exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche and Teva; speaker fees from the Swiss MS Society, Biogen, Genzyme, Merck, Novartis and Roche; travel expenses from Merck, Novartis and Roche; and grants from the ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer, Biogen, Genzyme, Merck, Novartis and Roche.
Jeffrey A. Cohen received personal compensation for consulting for Adamas, Convelo, EMD Serono, Novartis and Pendopharm; speaking for Mylan and Synthon; and serving as a co-editor of Multiple Sclerosis Journal - Experimental, Translational and Clinical.
Ludwig Kappos´ institution (University Hospital Basel) received in the last 3 years and used exclusively for research support at the department: steering committee, advisory board and consultancy fees from Actelion, Alkermes, Almirall, Bayer, Biogen, Celgene/Receptos, df-mp, Excemed, GeNeuro SA, Genzyme, Japan Tobacco, Merck, Minoryx, Mitsubishi Pharma, Novartis, Roche, Sanofi-Aventis, Santhera, Teva and Vianex; and royalties for Neurostatus UHB products; the Research of the MS Center in Basel has been supported by grants from Bayer, Biogen, Novartis, the Swiss MS Society, the Swiss National Research Foundation, the European Union and Roche Research Foundations.
Dieter A. Häring, Harald Kropshofer, David Leppert and Davorka Tomic are employees of Novartis.

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