Neurofilament light levels in the blood of patients with secondary progressive MS are higher than in primary progressive MS and may predict brain atrophy in both MS subtypes
ECTRIMS Online Library. Kappos L. Oct 12, 2018; 232039; 286
Prof. Dr. Ludwig Kappos
Prof. Dr. Ludwig Kappos
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Abstract: 286

Type: Scientific Session

Abstract Category: Clinical aspects of MS - Clinical assessment tools

Background: Neurofilament light chain (NfL) is considered a blood biomarker for monitoring neuronal damage, disease activity and treatment response in multiple sclerosis (MS). While the vast majority of studies on blood NfL concentrated on patients with relapsing-remitting MS (RRMS), little is known about blood NfL levels in patients with progressive MS.
Objective: To compare blood NfL baseline levels and to assess the prognostic potential of NfL for brain atrophy in patients with primary progressive MS (PPMS) and secondary progressive MS (SPMS) in placebo-controlled Phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND), respectively.
Method: Blood NfL levels in patients with SPMS (n=1452; mean age: 48.2 years; EDSS: 5.4) and patients with PPMS (n=378; mean age: 48.7 years; EDSS: 4.6) were retrospectively analysed. The NfL levels at baseline were quantified using Single Molecule Array technology and grouped into 3 categories (low: < 30, medium 30-60, high: > 60). High and low baseline NfL categories were compared using Chi-square and Wilcoxon rank sum tests. The association of baseline NfL levels with MRI parameters was done by Spearman rank correlation (Gd+ lesion count, T2 lesion volume) and the Jonckheere Terpstra test (brain volume change).
Results: NfL levels (Geometric mean, pg/mL) at baseline were higher in SPMS patients than in PPMS patients (32.1 vs 22.0, p< 0.001). A similar trend was observed when patients of the same age were compared: SPMS patients had higher NfL levels than those with PPMS. Similarly, patients with no Gd+ lesions at baseline had NfL levels of 29.2 and 21.0 in SPMS and PPMS, respectively, while patients with Gd+ lesions had NfL levels of 45.0 in SPMS and 34.0 in PPMS. The Gd+ lesion count (SPMS: r=0.33; PPMS: r=0.26) and T2 lesion volume (SPMS: r= 0.29; PPMS: r=0.32) at baseline correlated best with baseline NfL (p< 0.0001, all). In both SPMS and PPMS patients, high NfL at baseline was associated with higher percentage of brain volume loss at Month 12 (high NfL vs low NfL: −0.8% vs −0.2% in SPMS, p< 0.0001 and −0.8% vs −0.4% in PPMS, p=0.0044) and at Month 24 (−1.5% vs −0.5% in SPMS and −1.9% vs −0.8% in PPMS; both p< 0.0001).
Conclusion: Patients with SPMS showed evidence for more ongoing neuronal loss than PPMS patients of comparable age, both in the presence and in absence of Gd+ lesions. In both SPMS and PPMS patients, NfL may serve as a prognostic marker of brain atrophy.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
Jens Kuhle and Harald Kropshofer contributed equally.
Jens Kuhle's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, and Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, and Genzyme; travel expenses from Merck Serono, Novartis, and Roche; grants from the ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, and Roche.
Harald Kropshofer, Dieter A. Häring, Frank Dahlke, David Leppert, and Davorka Tomic are employees of Novartis Pharma AG.
Christian Barro has received travel support from Teva and Novartis.
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, Vianex and royalties for Neurostatus-UHB products. The Research of the MS Centre 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.

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