title: Efficacy and safety of belimumab in patients with rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled, dose-ranging Study.
abstract: OBJECTIVE
  To evaluate the efficacy/safety of belimumab in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Patients fulfilling American College of Rheumatology (ACR) criteria for RA for ≥ 1 year who had at least moderate disease activity while receiving stable disease-modifying antirheumatic drug (DMARD) therapy and failed ≥ 1 DMARD were randomly assigned to placebo or belimumab 1, 4, or 10 mg/kg, administered intravenously on Days 1, 14, and 28, and then every 4 weeks for 24 weeks (n = 283). This was followed by an optional 24-week extension (n = 237) in which all patients received belimumab. Primary efficacy endpoint was the Week 24 ACR20 response.
  
  
  RESULTS
  Week 24 ACR20 responses with placebo and belimumab 1, 4, and 10 mg/kg were 15.9%, 34.7% (p = 0.010), 25.4% (p = 0.168), and 28.2% (p = 0.080), respectively. Patients taking any belimumab dose who continued with belimumab in the open-label extension had an ACR20 response of 41% at 48 weeks. A similar ACR20 response (42%) at 48 weeks was seen in patients taking placebo who switched in the extension to belimumab 10 mg/kg. Greater response rates were observed in patients who at baseline were rheumatoid factor-positive, anticitrullinated protein antibody-positive, or tumor necrosis factor inhibitor-naive, or had elevated C-reactive protein levels, Disease Activity Score 28 > 5.1, or low B lymphocyte stimulator levels (< 0.858 ng/ml). Adverse event rates were similar across treatment groups.
  
  
  CONCLUSIONS
  In this phase II trial, belimumab demonstrated efficacy and was generally well tolerated in patients with RA who had failed previous therapies. [ClinicalTrials.gov identifier NCT00071812].
authors.affiliation: Division of Rheumatology, Los Angeles County + University of Southern California Medical Center and University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. stohl@usc.edu
authors.forename: William
authors.initials: W
authors.lastname: Stohl
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: James D
authors.initials: JD
authors.lastname: McKay
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Lisse
authors.forename: Z John
authors.initials: ZJ
authors.lastname: Zhong
authors.forename: William W
authors.initials: WW
authors.lastname: Freimuth
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D057915:Drug Substitution; D005260:Female; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D063189:Symptom Assessment / Q000379:methods; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C511911:belimumab
keywords: AUTOIMMUNE DISEASES; B LYMPHOCYTE STIMULATOR; BELIMUMAB; RHEUMATOID ARTHRITIS