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

Int J Rheum Dis. 2016 Nov;19(11):1103-1111. doi: 10.1111/1756-185X.12822. Epub 2015 Dec 22.

Abstract

Aims: 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.

Keywords: biologics; network meta-analysis; rheumatoid arthritis.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Abatacept / adverse effects
  • Abatacept / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Bayes Theorem
  • Biological Products / adverse effects
  • Biological Products / therapeutic use*
  • Drug Substitution
  • Humans
  • Network Meta-Analysis
  • Odds Ratio
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Rituximab / adverse effects
  • Rituximab / therapeutic use*
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Biological Products
  • Piperidines
  • Pyrimidines
  • Pyrroles
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Abatacept
  • tofacitinib
  • tocilizumab