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067 Neurofilament light chain concentration predicts risk of relapse in participants with relapsing multiple sclerosis in phase 3 ozanimod trials
  1. Sarah Harris1,
  2. Giancarlo Comi2,
  3. Bruce AC Cree3,
  4. Lawrence Steinman4,
  5. James K Sheffield1,
  6. Harry Southworth5,
  7. Ludwig Kappos6 and
  8. Jeffrey A Cohen7
  1. 1Bristol Myers Squibb, Princeton, New Jersey, USA
  2. 2Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
  3. 3Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA
  4. 4Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, California, USA
  5. 5Data Clarity Consulting Ltd, Stockport, UK
  6. 6Neurologic Clinic and Policlinic, University Hospital and University of Basel, Basel, Switzerland
  7. 7Department of Neurology, Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA


Objectives Plasma neurofilament light chain concentration (pNfL-c) is increased in patients with multiple sclerosis (MS) and may serve as a biomarker for neurologic damage and disease activity in relapsing MS. We analyzed changes in pNfL-c and on-treatment risk of relapse with ozanimod vs interferon β-1a (IFN).

Methods In this post hoc analysis of the phase 3 SUNBEAM (NCT02294058; ≥12 months) and RADIANCE (NCT02047734; 24 months) trials, pNfL-c was measured at baseline and after 12 and 24 months of treatment with oral ozanimod 0.46 or 0.92 mg/d or intramuscular IFN 30 µg/wk. Poisson generalized linear models were used to fit the number of relapses as a function of baseline pNfL-c and treatment group with an offset for duration. Predictive modeling of expected annualized relapse rate (ARR) was calculated using median percentage change in pNfL-c from baseline.

Results At end of treatment, median pNfL-c was reduced from baseline by 20%–23% (P<0.01) and 23%–27% (P≤0.0001) with ozanimod 0.46 and 0.92 mg, respectively, and by 13%–15% with IFN. Higher baseline pNfL-c was associated with more relapses (P<0.0001), and greater median reductions in pNfL-c from baseline were associated with lower ARR. Predictive modeling estimated that a 25% reduction in pNfL-c, similar to that observed with ozanimod 0.92 mg, predicts an ARR (standard error [SE]) of 0.18–0.23 (0.4), whereas a 13% reduction, similar to IFN, predicts an ARR (SE) of 0.29–0.37 (0.04).

Conclusion Our findings support pNfL-c as a biomarker for relapsing MS disease activity. Ozanimod caused greater dose-dependent reductions in pNfL-c and ARR than IFN.

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