Prognostic Value of On-treatment Serum Neurofilament Light Chain for New or Enlarging T2 Lesions in People with Relapsing Multiple Sclerosis: Pooled Analysis of the ASCLEPIOS I/II Trials
Thomas Leist1, Stephen Hauser2, Tobias Derfuss3, Heinz Wiendl4, Douglas Arnold5, Xavier Montalban6, Alit Bhatt7, Wenjia Wei8, Ibolya Boer8, Enrique Alvarez9, Tjalf Ziemssen10
1Thomas Jefferson University, Philadelphia, PA, USA, 2UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA, 3Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland, 4Institute of Translational Neurology, University of Münster, Münster, Germany, 5Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada, 6Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Vall d’Hebron University Hospital, Barcelona, Spain, 7Novartis Healthcare Pvt. Ltd., Hyderabad, India, 8Novartis Pharma AG, Basel, Switzerland, 9Rocky Mountain MS Center, University of Colorado School of Medicine, Aurora, CO, USA, 10Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
Objective:
To evaluate the prognostic value of 3- and 12-month on-treatment serum neurofilament light chain (sNfL) levels for future disease activity in people with relapsing multiple sclerosis (pwRMS).
Background:
In the Phase 3 ASCLEPIOS I/II trials (ofatumumab versus teriflunomide in pwRMS), baseline sNfL levels were prognostic for on-study lesion formation and brain volume loss in the overall population and in recently diagnosed treatment-naive participants. Here, we assess the prognostic value of on-treatment sNfL levels for future disease activity.
Design/Methods:
A baseline sNfL cut-off was predefined by the median sNfL value across the ASCLEPIOS I/II trials and participants were stratified into high (≥baseline median [≥9.3 pg/mL]) and low (<median) sNfL groups at Month (M) 3 and M12, irrespective of treatment received. The prognostic value of high versus low sNfL at M3 and M12 was analyzed for the annualized rate of new/enlarging T2 (neT2) lesions. The number of neT2 lesions on the last available scan relative to the M12 scan was analyzed in a negative binomial model with time (in years) between the two scans as offset, adjusting for sNfL category at the respective month.
Results:
Of the 1,882 participants randomized in ASCLEPIOS I/II, 1,393 and 1,384 participants had neT2 and sNfL data at M3 and M12, respectively. Participants with high versus low sNfL at M3 had a ~2.2-fold higher mean annualized rate of neT2 lesions (3.67 versus 1.69, rate ratio [RR]: 2.17; p<0.001). Similarly, participants with high versus low sNfL at M12 had a ~3.6-fold higher mean annualized rate of neT2 lesions (4.90 versus 1.37, RR: 3.57; p<0.001).
Conclusions:
On-treatment sNfL levels at 3 and 12 months continue to be prognostic for future lesion formation and support the use of sNfL as a prognostic biomarker for MS disease activity in pwRMS on disease-modifying therapy.