Janus Kinase Inhibitors and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis

Objective: To assess the risk of venous thromboembolism (VTE) in patients treated with Janus kinase (JAK) inhibitors in clinical trials. Patients and Methods: We performed a literature search of Ovid MEDLINE and ePub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily; Ovid EMBASE; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus, from inception to December 4, 2019, for randomized, placebo-controlled trials with JAK inhibitors as an intervention and reported adverse events. Odds ratio with 95% CI was calculated to estimate the VTE risk using a random effects model. Two independent reviewers screened and extracted data. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess certainty in estimated VTE risk. Results: We included 29 trials (13,910 patients). No statistically significant association was found between use of JAK inhibitors and risk of VTE (odds ratio, 0.91; 95% CI, 0.57 to 1.47; P=.70; I²=0; low certainty because of serious imprecision). Results using Bayesian analysis were consistent with those of the primary analysis. Results of stratified and meta-regression analyses suggested no interaction by dose of drug, indication for treatment, or length of follow-up. Conclusion: We found insufficient evidence to support an increased risk of JAK inhibitor–associated VTE based on currently available data.