NfL as a Predictor of GdE Lesions in Patients With Relapsing Multiple Sclerosis Treated With Ozanimod in the Phase 2 RADIANCE Trial
Sarah Harris1, Patrick Vermersch2, Xavier Montalban3, Hans-Peter Hartung4, Ludwig Kappos5, Harry Southworth6, James K. Sheffield1, Diego Silva1, Jeffrey A. Cohen7
1Bristol Myers Squibb, Princeton, New Jersey, 2Univ. Lille, Inserm UMR U1172, CHU Lille, FHU Precise, Lille, France, 3Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain, 4Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Sydney, Australia; Department of Neurology, Medical University of Vienna, Vienna, Austria; and Palacký University Olomouc, Olomouc, Czech Republic, 5Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland, 6Data Clarity Consulting Ltd, Stockport, England, United Kingdom, 7Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, Ohio
Objective:
To evaluate relationships between plasma neurofilament light chain (pNfL) and gadolinium-enhancing (GdE) lesion count in patients with relapsing multiple sclerosis (RMS) receiving ozanimod 0.92 mg in the phase 2 RADIANCE trial (NCT01628393).
Background:
In multiple sclerosis (MS) patients, increased blood and cerebrospinal fluid neurofilament light chain concentration may be a biomarker for neurologic damage and disease activity.
Design/Methods:
pNfL was measured at baseline and weeks 4, 12, and 24 using Simoa Nf-light digital immunoassay. GdE lesion counts were assessed from available MRI scans at baseline and weeks 8, 12, 16, 20, and 24. Predictive modelling was performed using penalized logistic regression on 100 bootstrap samples.
Results:
A pNfL decrease was observed at week 4 (median [Q1, Q3] % change from baseline: −7.891 [−18.933, 14.486]), with further decreases through week 24 (−15.883 [−32.039, 1.759], P<0.0001). GdE lesion counts were lower in patients receiving ozanimod vs placebo at week 8 (mean [SD] 1.096 [2.346] vs 2.267 [5.660]) and at week 24 (0.193 [0.594] vs 3.153 [9.984]). Patients who relapsed had higher baseline pNfL and week 24 GdE lesion counts than nonrelapsers (median [Q1, Q3] pNfL pg/mL: 11.597 [8.107, 14.474] vs 10.939 [7.541, 15.123]; mean [SD] GdE lesion count: 0.333 [0.707] vs 0.176 [0.582]). pNfL decreased from baseline more at week 4 in patients without vs with on-study relapses (median [Q1, Q3] % change from baseline: -7.891 [-19.475, 12.030] vs 0.389 [-17.513, 31.415]). Week 12 and 24 pNfL were the best predictors of week 24 GdE lesion count. Week 12 GdE lesion count was the best predictor of week 24 pNfL.
Conclusions:
Ozanimod 0.92 mg reduced pNfL from baseline and was associated with fewer GdE lesions than placebo in patients with RMS. pNfL at week 12 and week 24 predicted GdE lesion count at week 24; GdE lesion count at week 12 predicted pNfL at week 24.