Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis

作者：Amit Bar‐Or, Richard Grove, Daren Austin, Jerry M. Tolson, Susan VanMeter, Eric Lewis, Frederick J. Derosier, Monica C. Lopez, Sarah Kavanagh, Aaron Miller, Per Soelberg Sørensen · 发表于：Neurology · 年份：2018 · DOI：10.1212/wnl.0000000000005516 · 被引用次数：216 · 研究领域：Multiple Sclerosis Research Studies、Polyomavirus and related diseases、Viral Infections and Immunology Research

OBJECTIVE: To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS). METHODS: Patients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured. Safety monitoring continued weeks 24 to 48 with subsequent individualized follow-up evaluating B-cell repletion. RESULTS: < 0.001). Post hoc analysis (excluding weeks 1-4) estimated a ≥90% lesion reduction vs placebo (week 12) for all cumulative ofatumumab doses ≥30 mg/12 wk. Dose-dependent CD19 B-cell depletion was observed. Notably, complete depletion was not necessary for a robust treatment effect. The most common adverse event was injection-related reactions (52% ofatumumab, 15% placebo), mild to moderate severity in 97%, most commonly associated with the first dose and diminishing on subsequent dosing. CONCLUSION: Imaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data. This treatment effect also occurred with dosage regimens that only partially depleted circulating B cell...