Abstract
Objective: To evaluate serum neurofilament light (sNfL) as a prognostic and disease/treatment monitoring biomarker in multiple sclerosis (MS) patients utilizing a large well-characterized cohort of MS patients from Biogen Phase III clinical trials.
Background: sNfL is a promising biomarker of disease severity in MS. Evolution of sNfL into a clinical decision-making tool will require comprehensive data from larger well-characterized cohorts.
Design/Methods: sNfL levels were measured using a sensitive Single Molecule Array (SIMOA, Quanterix) assay in serial samples from >750 patients enrolled in three Phase III trials: CHAMPS (IFNβ1a in clinically isolated syndrome, CIS, n=319), ADVANCE (PEGylated-IFNβ1a in relapsing-remitting MS, RRMS, n=310), and SENTINEL (natalizumab in RRMS, n=122). Statistical analyses to evaluate associations between sNfL and key clinical and MRI parameters included Spearman correlation, ANOVA, chi-squared test, Kaplan-Meier analysis and multivariate logistic regression.
Results: sNfL levels were associated concurrently with number of enhancing lesions (p<0.00001) and T2 lesion volume (p<0.00001), as well as long-term with various clinical and paraclinical outcome measures, including EDSS progression (up to 5 years, p<0.05), T2 lesion volume and new T2 lesions (up to 10 years, p<0.00001), and brain atrophy (5 years p<0.00001). In patients with no evident disease activity, sNfL levels remained consistently low and stable (mean 8.4 pg/mL; mean within-patient coefficient of variation, CV=22%). In contrast, in patients with active disease, sNfL levels were elevated (mean 25 pg/mL) and more variable (CV=31%). Finally, sNfL levels were lowered in the experimental treatment arms, with the most pronounced effects observed for natalizumab. Detailed analyses describing effects of the treatments on sNfL will be presented.
Conclusions: These findings support the value of sNfL as a biomarker for disease severity and treatment monitoring in MS patients.
Study Supported by: This study was supported by Biogen (Cambridge, MA, USA).
Disclosure: Dr. Calabresi has nothing to disclose. Dr. Arnold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedDay, MedImmune, Mitsubishi, Novartis, Receptos/Celgene, Sanofi-Aventis. Dr. Arnold has received compensation for serving on the Board of Directors of NeuroRx Research. Dr. Kinkel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consulting, Scientific Advisory Board or speaking for Acorda, Biogen, Genzyme/Sanofi, Genentech, Novartis, Imstem, and CorTech. Dr. Singh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Singh holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Sangurdekar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Sangurdekar holds stock and/or stock options in Holds stock/stock options in Biogen. 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 Holds stock/stock options in Biogen. Dr. Engle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Engle holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Deykin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Deykin holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Fisher has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Fisher holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Sandrock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Sandrock holds stock and/or stock options in Holds stock/options in Biogen. Dr. Rudick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Rudick holds stock and/or stock options in Holds stock/stock options in Biogen. Dr. Kieseier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Kieseier holds stock and/or stock options in Holds stock/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. Dr. Plavina holds stock and/or stock options in Holds stock/stock options in Biogen.
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