ECTRIMS eLearning

Abstract: 262

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - Biomarkers

Introduction: Serum neurofilament light chain levels (sNfL) reflect neuroaxonal damage and disease activity in MS and may qualify as a biomarker of suboptimal response to disease modifying therapies (DMT).
Objective: To investigate the predictive value of sNfL in relapsing remitting (RR)MS patients with established DMT on future MS disease activity in the Swiss MS Cohort Study.
Methods: All patients were on continuous DMT between 3-24 months prior to baseline (BL) serum sampling and the entire follow-up (median 2.0 [IQR 1.1;3.0] years). BL and yearly follow-up sNfL were measured by Single Molecule Array (Simoa) assay in 569, 79 and 88 serum samples from 182, 27 and 28 patients on fingolimod, natalizumab or interferon beta or glatiramer acetate (IFN/GLAT), respectively. We used generalized estimating equation models (without and with a [drug*treatment duration] interaction term) to investigate the associations between clinical and treatment parameters and log sNfL. BL sNfL was dichotomized according to age-corrected percentile categories derived from 254 healthy controls (Disanto et al., 2017). Negative binominal regression models were used to compare relapse rates in the following two years and calculate incidence rate ratios (IRR).
Results: sNfL independently increased with age (2.1%/year [95%CI:1.4;2.7], p< 0.001), EDSS (5.7%/step,[1.6;9.9], p=0.006) and recent (< 120 days) relapse (19.4% [0.1;42.5], p=0.05), whereas sNfL decreased with time on DMT (-3.2%/year [-0.9;-5.5],p=0.006). This decrease was -12.8% [-4.7;-20.3] steeper in patients on natalizumab (p=0.003) and -6.8% [-1.8;-11.7] steeper in fingolimod patients (p=0.009) compared with patients on IFN/GLAT. Patients on fingolimod with BL sNfL levels above vs below [n above/below] the respective percentiles had increasingly higher relapse rates within the following two years (80^th percentile [43/139], IRR: 2.3 [1.1;4.9],p=0.036; 90^th [28/154]: 3.1 [1.4; 6.9],p=0.005; 95^th [19/163]: 4.1 [1.8; 9.5], p=0.001; 97.5^th [14/168]: 5.9 [2.6; 13.2],p< 0.001; 99^th [10/172]: 8.5 [4.0;18.3],p< 0.001), whereas there was no difference in the relapse rate one year before treatment start over all percentile cut-offs. A 10 pg/ml higher BL sNfL level (corrected for age, EDSS, previous on-treatment relapses) was associated with a 29% increase in relapse rate in the following two years (IRR:1.29 [1.16;1.43], p< 0.001).
Conclusion: Our data support the value of sNfL levels for treatment monitoring in MS clinical practice.
Disclosure:

• ÖY's institution University Hospital Basel received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung University Hospital Basel, Free Academy Basel, Swiss Multiple Sclerosis Society and advisory board fees from Sanofi Genzyme and Novartis Poland exclusively used for support of research and educational activities.
• CB has nothing to disclose.
• ZM has nothing to disclose.
• JV received honoraria for travel, honoraria for lectures/consulting and/or grants for studies from Allmiral, Biogen, Novartis, Teva, Merck-Serono, Genzyme, Roche and Bayer Schweiz AG
  
• AML has nothing to disclose.
• GD has nothing to disclose.
• AS received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, none related to this work.
• TD received speaker fees, research support, travel support, and/or served on Advisory Boards or Steering Committees of Novartis Pharma, Merck, Biogen, Teva, Bayer-Schering, GeNeuro, Mitsubishi Pharma, MedDay, Roche, and Genzyme; he received research support from Biogen, Novartis, Swiss National Research Foundation, University of Basel, and Swiss MS Society.
• CG has nothing to disclose.
• LA has nothing to disclose.
• OF has nothing to disclose.
• KN has nothing to disclose.
• CPK has received honoraria for lectures as well as research support from Biogen, Novartis, Almirall, Bayer Schweiz AG, Teva, Merck, Sanofi Genzyme, Roche, Celgene and the Swiss MS Society.
• CP has nothing to disclose.
• MS has nothing to disclose.
• RDP has nothing to disclose.
• VvW has nothing to disclose.
• JW is CEO of the Medical Image Analysis Center Basel.
• VV has nothing to disclose.
• AC has nothing to disclose.
• CZ´s institution the Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland receives financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis.
• CG´s instutition the Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland received financial support from Teva, Merck Serono, Biogen, Genzyme, Roche, Celgene, Bayer and Novartis.
• PHL received honoraria for speaking from Biogen-Idec, CSL Bering, Merck Serono, Novartis, Sanofi-Aventis, Teva; consulting fees from Biogen-Idec, Geneuro, Genzyme, Merck Serono , Novartis, Sanofi-Aventis, Teva; research grants from Biogen-Idec, Merck Serono, Novartis.

• SM received honoraria for travel, honoraria for lectures/consulting and/or grants for studies from Allmiral, Biogen, Celgene, Novartis, Teva, Merck-Serono, Genzyme, Roche and Bayer Schweiz AG
  

• LK's institution (University Hospital Basel) received and used exclusively for research support: steering committee, advisory board, and consultancy fees from Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Celgene/Receptos, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees from Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva; support of educational activities from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; grants from Bayer HealthCare, Biogen, F. Hoffmann-La Roche Ltd, Merck, Novartis, the European Union, the Roche Research Foundations, the Swiss Multiple Sclerosis Society, the Swiss National Research Foundation.
• PB has nothing to disclose.
• JK received speaker fees, research support, travel support, and/or served on advisory boards by ECTRIMS, Swiss MS Society, Swiss National Research Foundation, (320030_160221), University of Basel, Bayer, Biogen, Genzyme, Merck, Novartis, Protagen AG, Roche, Teva.