title: Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  This study aimed to assess the relative efficacy and safety of biologics and tofacitinib in patients with rheumatoid arthritis (RA) showing an inadequate response to tumor necrosis factor (TNF) inhibitors.
  
  
  METHODS
  We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with RA that inadequately responds to TNF inhibitors.
  
  
  RESULTS
  Four RCTs including 1796 patients met the inclusion criteria. The tocilizumab 8 mg group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the abatacept and tofacitinib groups. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab 8 mg had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9863), followed by rituximab (SUCRA = 0.6623), abatacept (SUCRA = 0.5428), tocilizumab 4 mg (SUCRA = 0.4956), tofacitinib 10 mg (SUCRA = 0.4715), tofacitinib 5 mg (SUCRA = 0.3415) and placebo (SUCRA = 0). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the treatment options.
  
  
  CONCLUSIONS
  Tocilizumab 8 mg was the second-line non-TNF biologic with the highest performance regarding an early good response based on ACR20 response rate and acceptable safety profile, followed by rituximab, abatacept and tofacitinib in patients with RA and an inadequate response to anti-TNF therapy, and none of these treatments were associated with a significant risk of withdrawal due to adverse events.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
mesh_terms: D000069594:Abatacept / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001499:Bayes Theorem; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D057915:Drug Substitution; D006801:Humans; D016017:Odds Ratio; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; D000069594:Abatacept; C479163:tofacitinib; C502936:tocilizumab
keywords: biologics; network meta-analysis; rheumatoid arthritis