Abstract: 158
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Serum neurofilament light chain (sNfL) is associated with disease activity, predicts long term clinical and imaging outcomes, and is reduced by disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (RRMS) patients. Integration of sNfL into clinical practice will require a standardized validated assay and defined clinically-meaningful cutpoints validated with real-world data.
Objectives: To define sNfL levels relevant to disease severity stratification and treatment monitoring in RRMS patients using samples and data from Biogen Phase III clinical studies.
Methods: sNfL was measured with a Single Molecule Array (SIMOA, Quanterix) Advantage kit or laboratory method in serial samples from >1000 patients enrolled in 4 studies. In ADVANCE [peginterferon beta-1a in RRMS, n=594], sNfL was measured at baseline (BL), every 3 months until year 2, then every 6 months until year 4; in CHAMPS [interferon beta 1a (IFNβ1a) in clinically isolated syndrome, n=319], at BL and week 48; in MSCRG (IFNβ1a in RRMS, n=164), at years 3 and 4; and in SENTINEL (natalizumab in RRMS, n=122), at BL and week 96. Statistical analyses included Spearman correlation, ANOVA, chi-squared test, Kaplan-Meier analysis, and multivariate logistic regression.
Results: BL sNfL levels were associated with number of enhancing lesions (p< 0.0001) and accumulation of new T2 lesions over time (p< 0.0001). Patients with no evident disease activity had consistently low sNfL levels, but those with active disease, especially with high brain atrophy rates, had elevated sNfL. sNfL>16 pg/mL indicated high probability of disease activity over the following year (PPV of 92% and 95% in test and verification cohorts, respectively); using the average of BL, months 3 and 6 sNfL further improved PPV. Similarly, sNfL>16 pg/mL was associated long-term with worse clinical and imaging outcomes: EDSS progression (12 years, p< 0.05), T2 lesion volume (10 years, p< 0.00001), and brain atrophy (5 years p< 0.00001). Finally, sNfL levels were lowered by DMTs; natalizumab reduced sNfL below 16 pg/mL in 96% of patients. The presentation will include discussion of assay characteristics to support clinical practice implementation.
Conclusions: These findings support the clinical relevance of sNfL levels and establish relevant cut-points for disease severity stratification and treatment monitoring in RRMS patients. Plans for introducing sNfL into clinical practice will be presented.
Disclosure: Study was sponsored by Biogen.
PAC reports consulting fees from Biogen, and grants from Biogen, MedImmune, Annexon, Teva, Genzyme, and Novartis.
JK Dr Kuhle's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche. DLA reports an equity interest in NeuroRx during the conduct of the study and consulting activities with Biogen, Celgene, Genentech, Genzyme, Hoffman-La Roche, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, as well as grants from Biogen and Novartis.
LK : Ludwig Kappos' institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; royalties from Neurostatus Systems GmbH and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
DS, CMS, CDM, BE, AD, EF, BCK, RAR and TP are employees of Biogen and hold stock/stock options in the company.
Abstract: 158
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Serum neurofilament light chain (sNfL) is associated with disease activity, predicts long term clinical and imaging outcomes, and is reduced by disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (RRMS) patients. Integration of sNfL into clinical practice will require a standardized validated assay and defined clinically-meaningful cutpoints validated with real-world data.
Objectives: To define sNfL levels relevant to disease severity stratification and treatment monitoring in RRMS patients using samples and data from Biogen Phase III clinical studies.
Methods: sNfL was measured with a Single Molecule Array (SIMOA, Quanterix) Advantage kit or laboratory method in serial samples from >1000 patients enrolled in 4 studies. In ADVANCE [peginterferon beta-1a in RRMS, n=594], sNfL was measured at baseline (BL), every 3 months until year 2, then every 6 months until year 4; in CHAMPS [interferon beta 1a (IFNβ1a) in clinically isolated syndrome, n=319], at BL and week 48; in MSCRG (IFNβ1a in RRMS, n=164), at years 3 and 4; and in SENTINEL (natalizumab in RRMS, n=122), at BL and week 96. Statistical analyses included Spearman correlation, ANOVA, chi-squared test, Kaplan-Meier analysis, and multivariate logistic regression.
Results: BL sNfL levels were associated with number of enhancing lesions (p< 0.0001) and accumulation of new T2 lesions over time (p< 0.0001). Patients with no evident disease activity had consistently low sNfL levels, but those with active disease, especially with high brain atrophy rates, had elevated sNfL. sNfL>16 pg/mL indicated high probability of disease activity over the following year (PPV of 92% and 95% in test and verification cohorts, respectively); using the average of BL, months 3 and 6 sNfL further improved PPV. Similarly, sNfL>16 pg/mL was associated long-term with worse clinical and imaging outcomes: EDSS progression (12 years, p< 0.05), T2 lesion volume (10 years, p< 0.00001), and brain atrophy (5 years p< 0.00001). Finally, sNfL levels were lowered by DMTs; natalizumab reduced sNfL below 16 pg/mL in 96% of patients. The presentation will include discussion of assay characteristics to support clinical practice implementation.
Conclusions: These findings support the clinical relevance of sNfL levels and establish relevant cut-points for disease severity stratification and treatment monitoring in RRMS patients. Plans for introducing sNfL into clinical practice will be presented.
Disclosure: Study was sponsored by Biogen.
PAC reports consulting fees from Biogen, and grants from Biogen, MedImmune, Annexon, Teva, Genzyme, and Novartis.
JK Dr Kuhle's institution (University Hospital Basel) received and used exclusively for research support: consulting fees from Biogen, Novartis, Protagen AG, Roche, Teva; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis, Roche; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer AG, Biogen, Genzyme, Merck, Novartis, Roche. DLA reports an equity interest in NeuroRx during the conduct of the study and consulting activities with Biogen, Celgene, Genentech, Genzyme, Hoffman-La Roche, MedImmune, Mitsubishi, Novartis, Receptos, Acorda, Sanofi-Aventis, as well as grants from Biogen and Novartis.
LK : Ludwig Kappos' institution (University Hospital Basel) has received in the last 3 years and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva; royalties from Neurostatus Systems GmbH and grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
DS, CMS, CDM, BE, AD, EF, BCK, RAR and TP are employees of Biogen and hold stock/stock options in the company.