| アブストラクト | 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: The cumulative number of new lesions was reduced by 65% for all ofatumumab dose groups vs placebo (p < 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 cells. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with RMS, ofatumumab decreases the number of new MRI gadolinium-enhancing lesions 12 weeks after treatment initiation. |
|---|
| 投稿者 | Bar-Or, Amit; Grove, Richard A; Austin, Daren J; Tolson, Jerry M; VanMeter, Susan A; Lewis, Eric W; Derosier, Frederick J; Lopez, Monica C; Kavanagh, Sarah T; Miller, Aaron E; Sorensen, Per S |
|---|
| 組織名 | From the Department of Neurology (A.B.-O.), Perelman School of Medicine,;University of Pennsylvania, Philadelphia; Neuroimmunology Unit (A.B.-O.),;Montreal Neurological Institute and Hospital, McGill University and McGill;University Health Center, Quebec, Canada; Neurosciences Clinical Statistics;(R.A.G.), Clinical Pharmacology (R.A.G., D.J.A.), and Modeling and Simulation;(D.J.A.), GlaxoSmithKline, Uxbridge, Middlesex, UK; Neurosciences Therapy Area;Unit (J.M.T., S.A.V., E.W.L., F.J.D., M.C.L., S.T.K.), SAVM (F.J.D., M.C.L.),;Global Clinical Safety and Pharmacovigilance (E.W.L.), and Neurosciences Clinical;Statistics (SecTK), GlaxoSmithKline, Research Triangle Park, NC; Department of;Neurology (A.E.M.), Corinne Goldsmith Dickinson Center for Multiple Sclerosis,;Icahn School of Medicine at Mount Sinai, New York, NY; and Danish Multiple;Sclerosis Center (P.S.S.), Department of Neurology, University of Copenhagen,;Rigshospitalet, Copenhagen, Denmark. Dr. Derosier is now at Clinical Development,;Isis Pharmaceutical, Carlsbad, CA. amitbar@upenn.edu.;Isis Pharmaceutical, Carlsbad, CA. |
|---|
