title: Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.
abstract: BACKGROUND
  An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations, we conducted a randomized, double-blind, controlled study.
  
  
  METHODS
  We randomly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments: oral methotrexate (> or =10 mg per week) (control); rituximab (1000 mg on days 1 and 15); rituximab plus cyclophosphamide (750 mg on days 3 and 17); or rituximab plus methotrexate. Responses defined according to the criteria of the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) were assessed at week 24 (primary analyses) and week 48 (exploratory analyses).
  
  
  RESULTS
  At week 24, the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria, the primary end point, was significantly greater with the rituximab-methotrexate combination (43 percent, P=0.005) and the rituximab-cyclophosphamide combination (41 percent, P=0.005) than with methotrexate alone (13 percent). In all groups treated with rituximab, a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria (65 to 76 percent vs. 38 percent, P< or =0.025) or had EULAR responses (83 to 85 percent vs. 50 percent, P< or =0.004). All ACR responses were maintained at week 48 in the rituximab-methotrexate group. The majority of adverse events occurred with the first rituximab infusion: at 24 weeks, serious infections occurred in one patient (2.5 percent) in the control group and in four patients (3.3 percent) in the rituximab groups. Peripheral-blood immunoglobulin concentrations remained within normal ranges.
  
  
  CONCLUSIONS
  In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48.
authors.affiliation: University College London, London, United Kingdom. jo.edwards@ucl.ac.uk
authors.forename: Jonathan C W
authors.initials: JC
authors.lastname: Edwards
authors.forename: Leszek
authors.initials: L
authors.lastname: Szczepanski
authors.forename: Jacek
authors.initials: J
authors.lastname: Szechinski
authors.forename: Anna
authors.initials: A
authors.lastname: Filipowicz-Sosnowska
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: David R
authors.initials: DR
authors.lastname: Close
authors.forename: Randall M
authors.initials: RM
authors.lastname: Stevens
authors.forename: Tim
authors.initials: T
authors.lastname: Shaw
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects*; D001424:Bacterial Infections / Q000209:etiology; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D008727:Methotrexate