We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
(DMT03) Efficacy and Safety of Ofatumumab Versus Teriflunomide in Patients with Relapsing Multiple Sclerosis: Phase 3 ASCLEPIOS I and II Trials.
- Authors
Cross, Anne H.; Kappos, Ludwig; Bar-Or, Amit; Cohen, Jeffrey A.; Comi, Giancarlo; Correale, Jorge; Coyle, Patricia K.; de Seze, Jerome; Leppert, David; Montalban, Xavier; Selmaj, Krzysztof W.; Wiendl, Heinz; Kerloeguen, Cecile; Willi, Roman; Bingbing Li; Kakarieka, Algirdas; Tomic, Davorka; Goodyear, Alexandra; Pingili, Ratnakar; Haering, Dieter A.
- Abstract
Background: Ofatumumab is the first fully human anti-CD20 monoclonal antibody, administered with a monthly 20 mg subcutaneous dosing regimen. Objectives: To investigate the efficacy and safety of ofatumumab vs teriflunomide in patients with relapsing multiple sclerosis (MS). Methods: ASCLEPIOS I and II were 2 identical phase 3, double-blind, double-dummy, active comparator-controlled, parallel-group, innovative, adaptive-design (with flexible duration), multicenter trials in patients aged 18-55 years with an Expanded Disability Status Scale score of 0-5.5 at screening. Patients were randomized (1:1) to receive subcutaneous ofatumumab 20 mg (loading dose: days 1, 7, and 14; maintenance dose: every 4 weeks from week 4) or oral teriflunomide 14 mg once daily, for up to 30 months. The primary end point was annualized relapse rate. Key secondary end points included 3- and 6-month confirmed disability worsening (3mCDW/6mCDW), 6-month confirmed disability improvement (6mCDI), magnetic resonance imaging--related outcomes, and serum neurofilament light chain (NfL) levels. Safety and tolerability were also assessed. Results: Of 1882 enrolled patients (ASCLEPIOS I/II: N = 927/955), 1578 completed the core study. Ofatumumab reduced annualized relapse rate (ASCLEPIOS I and II: 50.5% and 58.5%), gadolinium-enhancing T1 lesions (97.5% and 93.8%), and new/enlarging T2 lesions (82.0% and 84.5%) vs teriflunomide (all, P < .001). In the pre-specified ASCLEPIOS I/II pooled analysis, ofatumumab reduced the risk of 3mCDW by 34.4% (P = .002) and 6mCDW by 32.5% (P = .012), and numerically increased the probability to achieve 6mCDI by 35.2% (P = .094), vs teriflunomide. Ofatumumab reduced serum NfL levels vs teriflunomide in the first measurement at month 3 (ASCLEPIOS I, P = .011; ASCLEPIOS II, P < .001) and in all subsequent assessments (all, P < .001). No difference in the slope of brain volume change from baseline was observed between treatments (P = .116 [ASCLEPIOS I] and 0.129 [ASCLEPIOS II] vs teriflunomide). Adverse events occurred in 83.6% and 84.2% of patients receiving ofatumumab and teriflunomide, respectively. Systemic injection-related reactions occurred in 20.6% and 15.3% of ofatumumab and teriflunomide-treated patients, respectively. Rates of serious infections (ofatumumab, 2.5%; teriflunomide, 1.8%) and malignancies (0.5% and 0.3%, respectively) were low. Conclusions: Ofatumumab demonstrated superior efficacy vs teriflunomide, with an acceptable safety profile, in patients with relapsing MS.
- Subjects
BUTYRIC acid; CONFERENCES &; conventions; CROTON oil; MONOCLONAL antibodies; MULTIPLE sclerosis; PATIENT safety; DISEASE relapse; TREATMENT effectiveness
- Publication
International Journal of MS Care, 2020, Vol 22, Issue S2, p4
- ISSN
1537-2073
- Publication type
Article