title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, Copenhagen University Hospitals at Hvidovre and Glostrup, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. mo@dadlnet.dk
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.forename: Bo
authors.initials: B
authors.lastname: Baslund
authors.forename: William
authors.initials: W
authors.lastname: Rigby
authors.forename: Bernadette
authors.initials: B
authors.lastname: Rojkovich
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Peter T
authors.initials: PT
authors.lastname: Dawes
authors.forename: Charlotte
authors.initials: C
authors.lastname: Wiell
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: Søren C
authors.initials: SC
authors.lastname: Tamer
authors.forename: Helle
authors.initials: H
authors.lastname: Kastberg
authors.forename: Jørgen
authors.initials: J
authors.lastname: Petersen
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Sierakowski
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C527517:ofatumumab