title: Safety and efficacy of rituximab in patients with rheumatoid arthritis refractory to disease modifying antirheumatic drugs and anti-tumor necrosis factor-alpha treatment.
abstract: OBJECTIVE
  To determine the safety and efficacy of rituximab treatment in patients with active seropositive rheumatoid arthritis (RA) who had experienced an inadequate response to treatment with anti-tumor necrosis factor-alpha agents and/or traditional disease modifying antirheumatic drugs.
  
  
  METHODS
  Rituximab was administered to 17 patients as weekly infusions for 4 consecutive weeks. Patients continued their baseline therapy and were followed for 28 weeks.
  
  
  RESULTS
  All patients were evaluable for safety, and 13 for efficacy. Profound B cell depletion occurred by 12 weeks and was sustained at 24 weeks, whereas T cell, complement, and immunoglobulin levels remained within normal ranges. Rituximab was well tolerated, with no infusion related reactions and only mild/moderate adverse events. American College of Rheumatology 20% response (ACR20) was achieved in 55% of patients by Week 5, 75% by Week 8, 50% at Week 16, and 67% at Week 28. Corresponding ACR50 and ACR70 responses were achieved in 36% and 18%, 25% and 17%, 42% and 25%, and 33% and 17% of patients at Weeks 5, 8, 16, and 28, respectively. There were significant improvements over baseline in tender and swollen joint counts (p < 0.0001), physician's global assessment of disease activity (p = 0.0001), and patient assessed pain (p = 0.0005) and disability (p = 0.0386). Erythrocyte sedimentation rate (p = 0.0361) and rheumatoid factor titers (p < 0.0001) also decreased significantly.
  
  
  CONCLUSIONS
  These results support the hypothesis that B cells play an important role in RA pathophysiology, and suggest that rituximab is effective and well tolerated, with a rapid onset of clinical benefit, in patients with refractory, seropositive active RA.
authors.affiliation: Section of Rheumatology, Veterans Affairs, Northern California Health Care System, Sacramento, California, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Higashida
authors.forename: Ted
authors.initials: T
authors.lastname: Wun
authors.forename: Sara
authors.initials: S
authors.lastname: Schmidt
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Naguwa
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Tuscano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab