title: Clinical outcome in 22 patients with rheumatoid arthritis treated with B lymphocyte depletion.
abstract: OBJECTIVE
  To obtain evidence for dose response and to extend evidence of safety and efficacy for B lymphocyte depletion in rheumatoid arthritis.
  
  
  METHODS
  Twenty two patients with rheumatoid arthritis received a total of 29 treatments with five different combinations of rituximab (RTX), cyclophosphamide (CP), and/or high dose prednisolone (PR) on an open basis as follows; cohort I: RTX 1400 mg/m(2), CP 750x2+PR; cohort II: RTX 300-700 mg/m(2), -CP+/-PR); cohort III: RTX 600-700 mg/m(2), CP 750x2+PR; cohort IV: RTX 1200 mg/m(2), CP 750x2-PR; cohort V: RTX 500 mg/m(2), CP 750x2+PR. American College of Rheumatology (ACR) criteria of improvement at six months were chosen as the primary outcome measure. Disease activity scores and total duration of improvement and of B cytopenia were also recorded.
  
  
  RESULTS
  No major adverse events attributable to treatment were seen. ACR grades of improvement at six months were as follows: cohort I: ACR70x3, ACR50x2; cohort II: ACR20x1, ACR0x3; cohort III: ACR70x6, ACR50x2, ACR20x2; cohort IV: ACR70x2, ACR50x2, ACR20x1, ACR0x1; cohort V: ACR0x4.
  
  
  CONCLUSIONS
  B lymphocyte depletion in rheumatoid arthritis has so far proved to be safe and associated with major improvement with protocols including RTX 600 mg/m(2) or more and CP, but not with more limited protocols. These observations provide an initial basis for the design of formal trials of B cell depletion and other B cell directed treatments, including a phase II controlled trial now in progress.
authors.affiliation: Centre for Rheumatology, University College London, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Leandro
authors.forename: J C W
authors.initials: JC
authors.lastname: Edwards
authors.forename: G
authors.initials: G
authors.lastname: Cambridge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000628:therapy*; D001402:B-Lymphocytes / Q000187:drug effects*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D011239:Prednisolone