Contributions
Abstract: EP1613
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Serum Neurofilament light chain (sNfL) is a promising biomarker of neuro-axonal injury. Recent studies have shown associations with clinical and MRI disease activity and significant predictive value for relapses and worsening of disability. Follow up from patients with clinically isolated syndrome (CIS) who were enrolled in BENEFIT and had comprehensive assessments after 2, 5 and 11 years provides an opportunity to study the short- and long-term predictive value of sNfL.
Objective: To analyse the predictive capacity of baseline and year 1 sNfL measurements for outcomes at 2, 5 and 11 years. Further, to investigate associations between clinical and imaging variables and sNfL levels measured at baseline, 1 and 11 years.
Methods: Patients with CIS within 60 days were randomized to initial treatment with interferon beta-1b or placebo for 2 years or until diagnosis of clinically definite MS (CDMS). After conversion to CDMS or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Prospective follow up rater-blinded to initial randomization continued to year 5. Eleven years after randomization, patients were asked to participate in a comprehensive re-evaluation including clinical, imaging and blood laboratory tests. sNfL was measured by Single Molecule Array (Simoa) assay. The relation of sNfL to relapse-, disability- and MRI related endpoints at Years 2, 5 and 11 is investigated by uni- and multivariate regression analyses. Baseline covariates include sex; age; lowest EDSS up to Month 6 visit; mono/multifocal onset; presence of optic nerve, brainstem, or spinal cord lesions; PASAT3; Timed 25-Foot Walk and 9-Hole Peg test scores; number and volume of hypointense T1, gadolinium-enhancing T1, and T2 lesions; cerebral volume; and initial treatment assignment.
Results: sNfL was measured in 1018 samples (BL n=463; year 1, n=330, and year 11, n=225). Results of uni- and multivariate analyses will be presented.
Conclusions: Using the Simoa technology that allows highly sensitive and robust quantitation of sNfL levels our study will provide insights into the predictive value of sNfL for mid and long-term outcomes in patients with a first clinical inflammatory demyelinating event.
Disclosure:
- Study supported by Swiss National Research foundation and Bayer
- J 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.
- C Barro has received travel support from Teva and Novartis.
- G Edan has received honoraria for lectures or consulting from Biogen Idec, Merck Serono, and Sanofi-Aventis, and received personal compensation for serving on the BENEFIT scientific advisory board and for speaking from Bayer AG. He has also received research support from Serono, (a grant to University Hospital to support a research program on MRI in MS) and from Teva (a grant to support a research program on anti-IBF neutralizing antibodies).
- MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.
- H-P Hartung has received honoraria for consulting and speaking at symposia from Bayer AG, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and Sanofi-Aventis, with approval by the rector of Heinrich-Heine University.
- X Montalbán has received speaking honoraria and travel expenses for scientific meetings and has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
- F Barkhof has received compensation for consultancy from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Teva, and has received research support from the Dutch Foundation for MS research (an NGO).
- EJ Fox has received consulting fees, honoraria, travel, or research support from Acorda, Bayer, Biogen Idec, Eli Lilly, EMD Serono, Genzyme, GlaxoSmithKline, Novartis, Ono, Opexa Therapeutics, Pfizer, Roche, Sanofi, and Teva.
- B Hemmer has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of patients with MS and genetic determinants of neutralizing antibodies to interferon-beta.
- S Schippling has received research grants from Biogen, Bayer Healthcare, Novartis and Sanofi Genzyme, and consulting/speaker fees as well as travel support from Bayer Healthcare, Biogen, Merck Serono, Novartis, Teva, and Sanofi-Genzyme.
- R Koelbach is a salaried employee of PAREXEL International.
- EM Wicklein is a salaried employee of Bayer AG.
- L Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.
Abstract: EP1613
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Background: Serum Neurofilament light chain (sNfL) is a promising biomarker of neuro-axonal injury. Recent studies have shown associations with clinical and MRI disease activity and significant predictive value for relapses and worsening of disability. Follow up from patients with clinically isolated syndrome (CIS) who were enrolled in BENEFIT and had comprehensive assessments after 2, 5 and 11 years provides an opportunity to study the short- and long-term predictive value of sNfL.
Objective: To analyse the predictive capacity of baseline and year 1 sNfL measurements for outcomes at 2, 5 and 11 years. Further, to investigate associations between clinical and imaging variables and sNfL levels measured at baseline, 1 and 11 years.
Methods: Patients with CIS within 60 days were randomized to initial treatment with interferon beta-1b or placebo for 2 years or until diagnosis of clinically definite MS (CDMS). After conversion to CDMS or 2 years, patients on placebo could switch to interferon beta-1b or another treatment. Prospective follow up rater-blinded to initial randomization continued to year 5. Eleven years after randomization, patients were asked to participate in a comprehensive re-evaluation including clinical, imaging and blood laboratory tests. sNfL was measured by Single Molecule Array (Simoa) assay. The relation of sNfL to relapse-, disability- and MRI related endpoints at Years 2, 5 and 11 is investigated by uni- and multivariate regression analyses. Baseline covariates include sex; age; lowest EDSS up to Month 6 visit; mono/multifocal onset; presence of optic nerve, brainstem, or spinal cord lesions; PASAT3; Timed 25-Foot Walk and 9-Hole Peg test scores; number and volume of hypointense T1, gadolinium-enhancing T1, and T2 lesions; cerebral volume; and initial treatment assignment.
Results: sNfL was measured in 1018 samples (BL n=463; year 1, n=330, and year 11, n=225). Results of uni- and multivariate analyses will be presented.
Conclusions: Using the Simoa technology that allows highly sensitive and robust quantitation of sNfL levels our study will provide insights into the predictive value of sNfL for mid and long-term outcomes in patients with a first clinical inflammatory demyelinating event.
Disclosure:
- Study supported by Swiss National Research foundation and Bayer
- J 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.
- C Barro has received travel support from Teva and Novartis.
- G Edan has received honoraria for lectures or consulting from Biogen Idec, Merck Serono, and Sanofi-Aventis, and received personal compensation for serving on the BENEFIT scientific advisory board and for speaking from Bayer AG. He has also received research support from Serono, (a grant to University Hospital to support a research program on MRI in MS) and from Teva (a grant to support a research program on anti-IBF neutralizing antibodies).
- MS Freedman has received compensation from Bayer HealthCare, Biogen Idec, EMD Canada, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva Canada Innovation for consulting services. He also participates in a Genzyme-sponsored speakers bureau.
- H-P Hartung has received honoraria for consulting and speaking at symposia from Bayer AG, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and Sanofi-Aventis, with approval by the rector of Heinrich-Heine University.
- X Montalbán has received speaking honoraria and travel expenses for scientific meetings and has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Bayer, Biogen Idec, EMD, Genentech, Genzyme, Merck Serono, Neurotec, Novartis, Sanofi-Aventis, Teva Pharmaceuticals, and Almirall.
- F Barkhof has received compensation for consultancy from Bayer Schering Pharma, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis, Genzyme, Roche, and Teva, and has received research support from the Dutch Foundation for MS research (an NGO).
- EJ Fox has received consulting fees, honoraria, travel, or research support from Acorda, Bayer, Biogen Idec, Eli Lilly, EMD Serono, Genzyme, GlaxoSmithKline, Novartis, Ono, Opexa Therapeutics, Pfizer, Roche, Sanofi, and Teva.
- B Hemmer has served on scientific advisory boards for Roche, Novartis, Bayer Schering, and Genentech; has received speaker honoraria from Biogen Idec and Roche; and has received research support from Chugai Pharmaceuticals. He holds part of a patent for the detection of antibodies and T cells against KIR4.1 in a subpopulation of patients with MS and genetic determinants of neutralizing antibodies to interferon-beta.
- S Schippling has received research grants from Biogen, Bayer Healthcare, Novartis and Sanofi Genzyme, and consulting/speaker fees as well as travel support from Bayer Healthcare, Biogen, Merck Serono, Novartis, Teva, and Sanofi-Genzyme.
- R Koelbach is a salaried employee of PAREXEL International.
- EM Wicklein is a salaried employee of Bayer AG.
- L Kappos' institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: steering committee/consulting fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, and Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi-Aventis, and Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi-Aventis, and Teva; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen, the European Union, Merck, Novartis, Roche, Roche Research Foundations, the Swiss Multiple Sclerosis Society, and the Swiss National Research Foundation.