title: Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition.
abstract: BACKGROUND
  A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor alpha (TNF-alpha) inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti-TNF-alpha therapy.
  
  
  METHODS
  Patients with active rheumatoid arthritis and an inadequate response to anti-TNF-alpha therapy were randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one disease-modifying antirheumatic drug. Patients discontinued anti-TNF-alpha therapy before randomization. The rates of American College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of 20 percent or greater) and improvement in functional disability, as reflected by scores for the Health Assessment Questionnaire (HAQ) disability index, were assessed.
  
  
  RESULTS
  After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P<0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P<0.001; and 10.2 percent vs. 1.5 percent, P=0.003). At six months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3 percent, P<0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group.
  
  
  CONCLUSIONS
  Abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti-TNF-alpha therapy.
authors.affiliation: Stanford University Medical Center, Stanford, Calif, USA. genovese@stanford.edu
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Becker
authors.forename: Michael
authors.initials: M
authors.lastname: Schiff
authors.forename: Michael
authors.initials: M
authors.lastname: Luggen
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Sherrer
authors.forename: Joel
authors.initials: J
authors.lastname: Kremer
authors.forename: Charles
authors.initials: C
authors.lastname: Birbara
authors.forename: Jane
authors.initials: J
authors.lastname: Box
authors.forename: Kannan
authors.initials: K
authors.lastname: Natarajan
authors.forename: Isaac
authors.initials: I
authors.lastname: Nuamah
authors.forename: Tracy
authors.initials: T
authors.lastname: Li
authors.forename: Richard
authors.initials: R
authors.lastname: Aranda
authors.forename: David T
authors.initials: DT
authors.lastname: Hagerty
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
mesh_terms: D000069594:Abatacept; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007239:Infections / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept