Treatment of Myeloproliferative Neoplasms With Janus Kinase Inhibitors: A Meta-Analysis of Cardiovascular Safety

Abstract

Background

Janus kinase inhibitors (JAKis) are an integral aspect of the management of myeloproliferative neoplasms (MPNs). Part of the clinical benefit derived from JAKis may be due to reductions in thrombosis, a potentially life-threatening complication of MPNs. However, evidence has emerged of adverse cardiovascular effects secondary to JAKis. We conducted a first-of-a-kind meta-analysis of the cardiovascular safety of JAKis in the treatment of MPNs.

Methods

This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Systematic searches for studies comparing JAKi treatment to a control group were conducted. Studies reporting hypertension, major adverse cardiovascular events (MACE) and thromboembolic events were included in a meta-analysis using a random-effects model for the primary analysis, and fixed-effects model for any subgroup analyses performed.

Results

A total of 23 publications, consisting of nine clinical trials and one retrospective analysis, met the inclusion criteria. This resulted in a pooled population of 2198 patients (JAKi n = 1145, Control n = 1053). In studies reporting thromboembolic events (n = 9), pooled analysis revealed a significantly lower rate of thromboembolic events in the JAKi group (incidence rate ratio (IRR): 0.52, 95% CI: 0.28–0.98, p = 0.04). This was primarily driven by ruxolitinib studies in myelofibrosis (MF) and polycythemia vera (PV) as when a subgroup analysis of these trials was performed (n = 7), an even more significant reduction in thromboembolic events with JAKi treatment was found (IRR: 0.41, 95%CI: 0.26–0.64, p < 0.001). There was no significant difference in MACE or hypertension between JAKi and control groups.

Conclusion

This meta-analysis suggests that JAKi treatment of MPN was associated with a reduced risk of thromboembolic events; primarily driven by studies of ruxolitinib in PV and MF. Further prospective clinical trials are warranted to confirm these findings and characterise the cardiovascular profile of other JAKis and other types of MPNs.