title: Rituximab inhibits structural joint damage in patients with rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitor therapies.
abstract: OBJECTIVE
  To determine if treatment with a B cell-targeted therapy can inhibit the progression of structural joint damage in patients with rheumatoid arthritis (RA), exhibiting an inadequate response to tumour necrosis factor (TNF) inhibitors.
  
  
  METHODS
  In this phase III study, patients with an inadequate response to a TNF inhibitor and receiving methotrexate were randomised to rituximab or placebo. Radiographs were obtained at baseline, week 24 and week 56 after randomisation. Patients with an inadequate response to their randomised therapy could receive rescue medication from week 16. From week 24, eligible patients from both treatment arms could receive open-label rituximab. Patients were analysed according to their original treatment group. Radiographs were scored using the Genant-modified Sharp method. The primary radiographic endpoint was change in total Genant-modified Sharp score at week 56.
  
  
  RESULTS
  Rituximab treatment caused significant reduction in joint damage progression compared with placebo. The mean change from baseline in the total Genant-modified Sharp score at week 56 was significantly lower for patients treated with rituximab than for patients treated with placebo (1.00 vs 2.31; p = 0.005), and was supported by changes in erosion score (0.59 and 1.32 for rituximab plus methotrexate vs placebo plus methotrexate, respectively; p = 0.011) and joint space narrowing score (0.41 and 0.99, respectively; p<0.001).
  
  
  CONCLUSIONS
  This study provides the first evidence that a B cell-targeted therapy-rituximab-can significantly inhibit the progression of structural joint damage in patients with RA with long-standing, active and treatment-resistant disease.
authors.affiliation: Division of Rheumatology, University of Toronto, Toronto, Canada. edkeystone@mtsinai.on.ca
authors.forename: E
authors.initials: E
authors.lastname: Keystone
authors.forename: P
authors.initials: P
authors.lastname: Emery
authors.forename: C G
authors.initials: CG
authors.lastname: Peterfy
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
authors.forename: S
authors.initials: S
authors.lastname: Cohen
authors.forename: M C
authors.initials: MC
authors.lastname: Genovese
authors.forename: M
authors.initials: M
authors.lastname: Dougados
authors.forename: G R
authors.initials: GR
authors.lastname: Burmester
authors.forename: M
authors.initials: M
authors.lastname: Greenwald
authors.forename: T K
authors.initials: TK
authors.lastname: Kvien
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: D
authors.initials: D
authors.lastname: Hagerty
authors.forename: M W
authors.initials: MW
authors.lastname: Cravets
authors.forename: T
authors.initials: T
authors.lastname: Shaw
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011859:Radiography; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D008727:Methotrexate