0284: Compared Mortality and Cardiovascular Safety of JAK Inhibitors and Tocilizumab in Patients with RA : A Systematic Review and Network Meta-analysis
Background/Purpose: The ORAL-Surveillance trial showed important data on the comparative safety between Tofacitinib and TNF inhibitors (TNFi) in the treatment of RA, leading to safety concerns about JAK inhibitors. Little is known, however, about comparative safety data between other bDMARD non-TNFi or even JAKi other than Tofacitinib. Our aim was to compare the risk of all-cause death (ACD) and major adverse cardiovascular events (MACE) in individuals with RA treated with tocilizumab (TCZ) or JAK inhibitors (JAKi).
Methods: Methods: We performed a systematic review within 6 medical databases until 1st June 2022 for phase 2-4 RCTs evaluating patients with RA treated with JAKi (Tofacitinib, Baricitinib or Upadacitinibe) or TCZ (intervention arm) compared to controls (TNFi or placebo). Study data were independently assessed by 3 investigators. We performed a network meta-analysis with additive and random effecs to evaluate the risk of MACE (primary outcome) and ACD (secondary outcome) compared to TNFi. We calculated posterior probability of increasing the primary and secondary outcomes following Bayes' Theorem.
Results: The meta-analysis included 19 RCTs, with 19,074 patients and 54,713 patients-years. TCZ and JAKi were linked to non statistically significant increase in the risk of MACE as compared to TNFi (ORs of 1.0669 [95%CI 0.7896; 1.4414; p=0.673] and 1.2712 [0.8970; 1.8014]; p=0.177], respectively [I2 = 0%]), whereas the posterior probabilities of increasing MACE by 15% or more were 21% and 83%. TCZ and JAKi were also linked to non statistically significant increase in the risk of ACD as compared to TNFi (ORs of 1.3526 [0.6283; 2.9117; p=0.44] and 1.2044 [0.5611; 2.5852; p=0.633], respectively [I2 = 9%]), with posterior probabilities of increasing ACD by 15% or more were 81% and 61%.
Conclusion: Conclusion: This meta-analysis found a substatial probability ( >60%) that JAKi increase the risk of MACE and ACD, and that TCZ increase risk of ACD compared to TNFi. Our results reinforce the need for new clinical trials of comparative safety between IJAK, TNFi and non-TNF bDMARD.
