Dr. Østergaard has received consulting fees, speaking fees, and/or honoraria from Genmab (less than $10,000).
Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: Results of a randomized, double-blind, placebo-controlled, phase I/II study†
Article first published online: 19 APR 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 8, pages 2227–2238, August 2010
How to Cite
Østergaard, M., Baslund, B., Rigby, W., Rojkovich, B., Jorgensen, C., Dawes, P. T., Wiell, C., Wallace, D. J., Tamer, S. C., Kastberg, H., Petersen, J. and Sierakowski, S. (2010), Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: Results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis & Rheumatism, 62: 2227–2238. doi: 10.1002/art.27524
ClinicalTrials.gov identifier: NCT00291928.
- Issue published online: 3 AUG 2010
- Article first published online: 19 APR 2010
- Manuscript Accepted: 13 APR 2010
- Manuscript Received: 16 MAR 2009
- Genmab, Copenhagen, Denmark
To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to ≥1 disease-modifying antirheumatic drug.
This combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated.
AEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24.
Our findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.