Table 3.
Systematic Reviews Assessing Venous Thromboembolism Risk in Patients Treated with Janus Kinase Inhibitors
| First Author | Year | Number of Studies | Inclusion Criteria | Main Outcomes |
|---|---|---|---|---|
| Alves et al79 | 2022 | 42 | RA RCTs of baricitinib, filgotinib, peficitinib, tofacitinib, and upadacitinib. | No differences were observed between different JAKis regarding the risk of VTE compared with placebo |
| Bilal et al80 | 2021 | 29 | RCTs of JAK inhibitors, regardless of clinical condition, that reported adverse event data for the treatment and control groups | No association between the use of JAK inhibitors and the risk of VTE (odds ratio, 0.91; 95% CI, 0.57 to 1.47), even when cancer studies were excluded and analysis was stratified according to underlying disease. |
| Giménez et al81 | 2020 | 59 | RCTs and non-RCTs and controlled cohort studies (prospective or retrospective) comparing oral baricitinib or tofacitinib at any dose with another active drug or placebo in which patients received at least one dose of oral baricitinib or tofacitinib for any indication. | Overall, an odds ratio (OR) for VTE events of 0.29 (95% CI 0.10–0.84) for tofacitinib. -The ORs for VTE events for baricitinib was 3.39 (95% CI 0.82–14.04) overall. -The indirect meta-analysis comparing tofacitinib with baricitinib showed an OR for VTE events of 0.086 (95% CI 0.02–0.51) for tofacitinib and a superior safety profile for VTE events. -In the meta-regression analysis, the effect was 0.02 (95% CI −0.04 to 0.08) for tofacitinib and 0.01 (95% CI −1.29 to 1.26 for baricitinib. -Plotting data for tofacitinib showed that VTE risk increased with high doses. -The effect, however, was less than 1 for the 10- and 20-mg doses, indicating a protective effect. This effect was not observed for baricitinib. |
| Yates et al82 | 2020 | 42 | RCTs of JAKi therapy with a placebo comparator arm | IRR of VTE, PE and DVT in patients receiving JAKi were 0.68 (95% CI 0.36 to 1.29), 0.44 (95% CI 0.28 to 0.70) and 0.59 (95% CI 0.31 to 1.15), respectively. |
| Wang et al83 | 2020 | 20 | RTCs of tofacitinib or baricitinib, or upadacitinib in RA patients | VTE data were unavailable for tofacitinib or baricitinib, but there was no increase in risk with upadacitinib (15 mg daily: RR, 2.34; 95% CI, 0.34 to 15.92). |
| Xie et al84 | 2019 | 29 | RCTs in adult patients with immune-mediated inflammatory disorders using tofacitinib | There was a decreased rate of VTEs (OR 0.03, 95% CI 0.00–0.21) in patients initiating tofacitinib. Tofacitinib 10 twice daily was associated with an increase in VTEs risk (OR = 1.47, 95% CI 0.25–8.50) compared with the 5 mg regimen. |
| Xie et al | 2019 | 25 for placebo comparison 18 for dose dependence |
RTCs of tofacitinib or baricitinib, or upadacitinib in RA patients | There was no increased risk of VTEs in users of the 3 JAKi (OR 1.16 (0.48 to 2.81), p = 0.74). There was no dose dependent increase of VTE in any JAKi |
Abbreviations: RCT, randomized controlled trial; RA, rheumatoid arthritis; JAKi, Janus kinase inhibitor; VTE, venous thromboembolism; DVT, deep venous thrombosis; PE, pulmonary embolism; CI, confidence interval; OR, odds ratio; RR, relative risk; HR, hazard ratio; IR, incident rate.