title: Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis).
  
  
  METHODS
  Patients-categorised as TNFi-naive, TNFi-previous (washout) or TNFi-recent (no washout) -received open-label tocilizumab (8 mg/kg) every 4 weeks ± DMARDs for 24 weeks. Adverse events (AEs) and treatment discontinuations were monitored. Efficacy end points included American College of Rheumatology (ACR) responses, 28-joint disease activity score (DAS28) and European League Against Rheumatism responses.
  
  
  RESULTS
  Overall, 1681 (976 TNF-naive, 298 TNFi-previous and 407 TNFi-recent) patients were treated; 5.1% discontinued treatment because of AEs. The AE rate was numerically higher in TNFi-recent (652.6/100 patient-years (PY)) and TNFi-previous (653.6/100PY) than in TNFi-naive (551.1/100PY) patients. Serious AE rates were 18.0/100PY, 28.0/100PY and 18.6/100PY; serious infection rates were 6.0/100PY, 6.8/100PY and 4.2/100PY, respectively. At week 4, 36.5% of patients achieved ACR20 response and 14.9% DAS28 remission (<2.6); at week 24, 66.9%, 46.6%, 26.4% and 56.8% achieved ACR20/ACR50/ACR70 responses and DAS28 remission, respectively. Overall, 61.6% (TNFi-naive), 48.5% (TNFi-previous) and 50.4% (TNFi-recent) patients achieved DAS28 remission.
  
  
  CONCLUSIONS
  In patients with RA who were DMARD-IR/TNFi-IR, tocilizumab ± DMARDs provided rapid and sustained efficacy without unexpected safety concerns.
authors.affiliation: Inflammatory Arthritis Center, Hospital for Special Surgery, New York, NY 10021, USA. bykerkv@hss.edu
authors.forename: Vivian P
authors.initials: VP
authors.lastname: Bykerk
authors.forename: Andrew J K
authors.initials: AJ
authors.lastname: Ostör
authors.forename: José
authors.initials: J
authors.lastname: Alvaro-Gracia
authors.forename: Karel
authors.initials: K
authors.lastname: Pavelka
authors.forename: José Andrés Román
authors.initials: JA
authors.lastname: Ivorra
authors.forename: Winfried
authors.initials: W
authors.lastname: Graninger
authors.forename: William
authors.initials: W
authors.lastname: Bensen
authors.forename: Michael T
authors.initials: MT
authors.lastname: Nurmohamed
authors.forename: Andreas
authors.initials: A
authors.lastname: Krause
authors.forename: Corrado
authors.initials: C
authors.lastname: Bernasconi
authors.forename: Andrea
authors.initials: A
authors.lastname: Stancati
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; C502936:tocilizumab