Long-term Effect of Ofatumumab Treatment on Serum Neurofilament Light Chain Levels and NEDA-3 Status in Patients With RMS: Results From ASCLEPIOS I/II and ALITHIOS
Enrique Alvarez1, Jens Kuhle2, Ludwig Kappos3, Tjalf Ziemssen4, Douglas Arnold5, Anne Cross6, Ibolya Boer7, Ayan Das Gupta8, Xixi Hu9, Petra Kukkaro7, Bernd Kieseier7, Ronald Zielman10, Stephen Hauser11
1Department of Neurology, Rocky Mountain MS Center at the University of Colorado, 2Neurology, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, 3Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) and MS Center, Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, 4Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl Gustav Carus, 5McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University and NeuroRx Research, 6Washington University School of Medicine, 7Novartis Pharma AG, 8Novartis Healthcare, 9Novartis Pharmaceuticals Corporation, 10Novartis Pharma B.V., 11UCSF Weill Institute for Neurosciences, University of California, San Francisco
Objective:
To assess the long-term effect of ofatumumab (OMB; anti-CD20 monoclonal antibody) on serum neurofilament light chain (sNfL) levels and 3-parameter no evidence of disease activity (NEDA-3) in patients with relapsing multiple sclerosis receiving continuous OMB and those converted from teriflunomide (TER) in ASCLEPIOS I/II (core; NCT02792218/NCT02792231) and ALITHIOS (open-label extension; NCT03650114).
Background:
In ASCLEPIOS I/II, OMB lowered sNfL levels vs TER over 96 weeks and increased the likelihood of achieving NEDA-3 in Years 1 and 2 (Y1/Y2).
Design/Methods:
We analyzed cumulative data from patients randomized to OMB/TER (946/936) in ASCLEPIOS I/II (pooled) who continued OMB (OMB-OMB; 690) or converted from TER to OMB (TER-OMB; 677) in ALITHIOS. Between-group comparisons of geometric mean sNfL levels over time and proportion of patients achieving NEDA-3 were evaluated.
Results:
In ASCLEPIOS I/II, sNfL levels (pg/mL) were reduced with OMB vs TER (month [M] 12, 8.03 vs 10.25; M24, 7.96 vs 9.97; both p<0.001). Continuous OMB treatment maintained low sNfL levels in ALITHIOS (M24, 8.50). Converting from TER to OMB significantly reduced sNfL levels vs OMB-OMB up to M6 after switch (9.07 vs 8.31; p<0.001). Low sNfL levels were observed in both groups from M12 onward (M24, 8.23 vs 8.50). In ASCLEPIOS I/II, OMB treatment resulted in an ~3-fold higher likelihood of achieving NEDA-3 vs TER during Y1 (48% vs 25.2%; OR [95% CI], 3.39 [2.71-4.25]; p<0.001) and 10-fold higher likelihood during Y2 (85% vs 38.4%; 10.09 [7.82-13.02]; p<0.001). In ALITHIOS, ~8/10 patients in OMB-OMB and 6/10 patients in TER-OMB achieved NEDA-3 in Y1 (85.8% vs 59.5%; 4.50 [3.40-5.94]; p<0.001). NEDA-3 achievement during Y2 was similar in OMB-OMB and TER-OMB (86.4% vs 90.4%; 1.55 [1.07-2.22]; p=0.019).
Conclusions:
A near complete and sustained suppression of disease activity was achieved with early and continuous use of OMB, and a rapid reduction in disease activity followed conversion from TER to OMB.