PMID- 20506254 OWN - NLM STAT- MEDLINE DCOM- 20100903 LR - 20191210 IS - 1529-0131 (Electronic) IS - 0004-3591 (Linking) VI - 62 IP - 8 DP - 2010 Aug TI - 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. PG - 2227-38 LID - 10.1002/art.27524 [doi] AB - OBJECTIVE: 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 > or = 1 disease-modifying antirheumatic drug. METHODS: 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 (i.v.) 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. RESULTS: 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. CONCLUSION: Our findings indicate that ofatumumab, administered as 2 i.v. infusions of doses up to 1,000 mg, is clinically effective in patients with active RA. FAU - Ostergaard, Mikkel AU - Ostergaard M AD - Department of Rheumatology, Copenhagen University Hospitals at Hvidovre and Glostrup, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. mo@dadlnet.dk FAU - Baslund, Bo AU - Baslund B FAU - Rigby, William AU - Rigby W FAU - Rojkovich, Bernadette AU - Rojkovich B FAU - Jorgensen, Christian AU - Jorgensen C FAU - Dawes, Peter T AU - Dawes PT FAU - Wiell, Charlotte AU - Wiell C FAU - Wallace, Daniel J AU - Wallace DJ FAU - Tamer, Soren C AU - Tamer SC FAU - Kastberg, Helle AU - Kastberg H FAU - Petersen, Jorgen AU - Petersen J FAU - Sierakowski, Stanislaw AU - Sierakowski S LA - eng SI - ClinicalTrials.gov/NCT00291928 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - M95KG522R0 (ofatumumab) SB - IM CIN - Arthritis Rheum. 2011 Jan;63(1):305; author reply 305. PMID: 20967857 MH - Antibodies, Monoclonal/administration & dosage/adverse effects/*therapeutic use MH - Antibodies, Monoclonal, Humanized MH - Antirheumatic Agents/administration & dosage/adverse effects/therapeutic use MH - Arthritis, Rheumatoid/*therapy MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Humans MH - Male MH - Middle Aged MH - Patient Selection MH - Severity of Illness Index MH - Treatment Outcome EDAT- 2010/05/28 06:00 MHDA- 2010/09/04 06:00 CRDT- 2010/05/28 06:00 PHST- 2010/05/28 06:00 [entrez] PHST- 2010/05/28 06:00 [pubmed] PHST- 2010/09/04 06:00 [medline] AID - 10.1002/art.27524 [doi] PST - ppublish SO - Arthritis Rheum. 2010 Aug;62(8):2227-38. doi: 10.1002/art.27524.