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Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).
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.
Arthritis Res Ther. 2015 Dec 15;17:362
Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials
Vibeke Strand et al.
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