Venous thromboembolism risk with JAK inhibitors: A Meta-analysis.

Yates, Mark; Mootoo, Amanda; Adas, Maryam; Bechman, Katie; Rampes, Sanketh; Patel, Vishit; Qureshi, Sumera; Cope, Andrew P; Norton, Sam; Galloway, James B

OBJECTIVES Janus Kinase inhibiting therapies (JAKi) are effective treatment options for immune mediated inflammatory diseases (IMIDs). Their use has been limited by venous thromboembolism (VTE) risk warnings from licensing authorities. The objective was to evaluate the VTE risk of JAKi in patients with IMIDs. METHODS Systematic searches of MEDLINE and EMBASE databases from inception to 30th September 2020 were conducted. Phase II and III double blinded randomized controlled trials (RCTs) of JAKi at licensed doses were included. RCTs with no placebo arm, Long term extension studies, post hoc, and pooled analyses were excluded. Three researchers independently extracted data on JAKi and placebo exposure and VTE (pulmonary emboli and deep vein thromboses) events and assessed study quality. RESULTS A total of 42 studies were included, from an initial search of 619. There were 6,542 JAKi patient exposure years (PEY), compared to 1,578 placebo PEY. There were 15 VTE events in the JAKi group and four in the placebo group. The pooled Incidence rate ratio (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. CONCLUSION This meta-analysis of RCT data defines the VTE risk with JAKi as a class in IMID patients. The pooled IRR do not support current warnings around VTE risk for JAKi. The findings will aid continued development of clinical guidelines for the use of JAKi in IMIDs.