This analysis depicts the difference in the incidence of infections between the different populations based on individual exposure information for tofacitinib. Also, concomitant corticosteroid intake results in increase in the risk of serious infections with the biologic disease-modifying antirheumatic drug (−inadequate responder (DMARDs).

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib modulates the signaling of cytokines that are integral to lymphocyte activation, proliferation, and function. Thus, tofacitinib therapy may result in suppression of multiple elements of the immune response. Serious infections have been reported in tofacitinib RA trials. However, limited head-to-head comparator data were available within the tofacitinib RA development program to directly compare rates of serious infections with tofacitinib relative to biologic agents, and specifically adalimumab (employed as an active control agent in two randomized controlled trials of tofacitinib).

The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95 % confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95 % CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95 % CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95 % CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38 % (−0.24 %, 0.99 %) and 0.40 % (−0.22 %, 1.02 %), respectively.

The search produced 657 hits. In total, 66 randomized controlled trials and 22 long-term extension studies met the selection criteria. Estimated incidence rates (95 % confidence intervals [CIs]) for abatacept, rituximab, tocilizumab, and tumor necrosis factor inhibitors were 3.04 (2.49, 3.72), 3.72 (2.99, 4.62), 5.45 (4.26, 6.96), and 4.90 (4.41, 5.44), respectively. Incidence rates (95 % CIs) for tofacitinib 5 and 10 mg twice daily (BID) in phase 3 trials were 3.02 (2.25, 4.05) and 3.00 (2.24, 4.02), respectively. Corresponding incidence rates in long-term extension studies were 2.50 (2.05, 3.04) and 3.19 (2.74, 3.72). The risk ratios (95 % CIs) versus placebo for tofacitinib 5 and 10 mg BID were 2.21 (0.60, 8.14) and 2.02 (0.56, 7.28), respectively. Risk differences (95 % CIs) versus placebo for tofacitinib 5 and 10 mg BID were 0.38 % (−0.24 %, 0.99 %) and 0.40 % (−0.22 %, 1.02 %), respectively.

In interventional studies, the risk of serious infections with tofacitinib is comparable to published rates for biologic disease-modifying antirheumatic drugs in patients with moderate to severely active RA.