title: Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  The efficacy and safety of subcutaneous tocilizumab (TCZ-SC) versus subcutaneous placebo (PBO-SC) was evaluated in patients with rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs in the BREVACTA study.
  
  
  METHODS
  Patients (n = 656) were randomized 2:1 to receive TCZ-SC 162 mg every other week or PBO-SC every other week for 24 weeks; 20% previously received anti-tumor necrosis factor treatment. Escape therapy with TCZ-SC 162 mg weekly was offered from week 12 for inadequate response. The primary end point was the American College of Rheumatology 20% improvement (ACR20) response at week 24. The key secondary outcomes were radiographic progression and safety.
  
  
  RESULTS
  TCZ-SC was superior to PBO-SC for ACR20 response at week 24 (60.9% versus 31.5%; P < 0.0001). All secondary end points showed TCZ-SC to be superior to PBO-SC, including ACR50 and ACR70 response (40% and 20% for TCZ-SC, respectively, and 12% and 5% for PBO-SC, respectively; P < 0.0001 for both) and Disease Activity Score in 28 joints (DAS28) remission (DAS28 <2.6; 32% versus 4% [P < 0.0001]). The mean change in modified Sharp/van der Heijde score was significantly lower in the TCZ-SC group than the PBO-SC group (0.62 versus 1.23; P = 0.0149). Adverse events (AEs) and serious AEs (SAEs) were comparable between the TCZ-SC and PBO-SC groups; 4.6% and 3.7% of patients had at least 1 SAE, respectively, and infection was the most common SAE in 2.1% and 1.8% of patients, respectively. More injection site reactions occurred with TCZ-SC than PBO-SC (7.1% versus 4.1%). No anaphylaxis or serious hypersensitivity reactions occurred. There were 3 deaths in the TCZ-SC group and 0 in the PBO-SC group.
  
  
  CONCLUSIONS
  TCZ-SC every other week had significantly greater efficacy, including ACR end points and inhibition of joint damage, compared with PBO-SC. TCZ-SC was well tolerated and its safety profile was comparable with that of previous intravenous TCZ studies.
authors.affiliation: Altoona Center for Clinical Research, Duncansville, Pennsylvania.
authors.forename: Alan
authors.initials: A
authors.lastname: Kivitz
authors.forename: Ewa
authors.initials: E
authors.lastname: Olech
authors.forename: Michael
authors.initials: M
authors.lastname: Borofsky
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Zazueta
authors.forename: Federico
authors.initials: F
authors.lastname: Navarro-Sarabia
authors.forename: Sebastião C
authors.initials: SC
authors.lastname: Radominski
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: Lucy
authors.initials: L
authors.lastname: Rowell
authors.forename: Clare
authors.initials: C
authors.lastname: Nasmyth-Miller
authors.forename: Min
authors.initials: M
authors.lastname: Bao
authors.forename: Stephen
authors.initials: S
authors.lastname: Wright
authors.forename: Janet E
authors.initials: JE
authors.lastname: Pope
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D019947:Receptors, Interleukin-6; C502936:tocilizumab