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JAK inhibitor treatment is associated with a reduction in risk of thromboembolic events for patients with myeloproliferative neoplasms.
Treatment with Janus kinase inhibitors (JAKis) has been found to be associated with a reduction in risk of thromboembolic events among patients with myeloproliferative neoplasms (MPNs), according to research findings.
These findings were published in eJHaem, and are driven by observations of treatment with Jakafi (ruxolitinib) for patients with polycythemia vera and myelofibrosis, researchers noted.
“In this meta-analysis, JAKi [used for] MPN [treatment] was associated with a reduced risk of thromboembolic events compared [with] control, primarily driven by studies of [Jakafi] in polycythemia vera and myelofibrosis,” first study author Roberta Dunn and colleagues wrote in the study. “JAKi treatment was not associated with an increased risk of [major adverse cardiovascular events] or hypertension, adding to the existing body of evidence demonstrating the safety of JAKi in the treatment of MPNs. Further prospective clinical trials are warranted to confirm these findings and characterize the cardiovascular profile of other JAKis in all types of MPNs.”
Thromboembolic events: A thromboembolism, according to the Cleveland Clinic, is a circulating blood clot that gets stuck and causes an obstruction.
Major adverse cardiovascular events: A composite measure of cardiovascular adverse events frequently used in
clinical trials, according to Dunn and her co-authors.
Hypertension: High blood pressure.
Dunn is a medical student at the School of Medical Education, King’s College London, as well as a student researcher at Guy's and St Thomas' NHS Foundation Trust, in the United Kingdom.
MPNs, according to the Cleveland Clinic, are rare blood cancers that involve the patient’s body making too many red blood cells, white blood cells or platelets. JAKis, as explained by the National Cancer Institute, block the actions of enzymes which control cell signaling and growth, the number of blood cells and platelets made in the bone marrow, inflammation, and immune cell activity. Blocking these enzymes may help prevent abnormal blood cells or cancer cells from growing.
While JAKis were first approved by the Food and Drug Administration in 2011 for the treatment of adults with myelofibrosis, researchers noted that increases have been observed in body weight and cholesterol levels secondary to treatment with JAKis, both of which are risk factors for cardiovascular disease. Notably, one clinical trial, PERIST-2, was prematurely terminated due to bleeding and cardiovascular events in the JAKi arm.
In this meta-analysis, Dunn and colleagues reviewed data from 23 publications consisting of nine clinical trials and one retrospective analysis, resulting in a pooled population of 2,198 patients. In total, 1,145 were treated with JAKis and 1,053 in the control group.
Researchers shared that that in the nine studies reporting thromboembolic events, a pooled analysis revealed a significantly lower rate of thromboembolic events in the JAKi group, with a 48% reduction in such events. Under a subgroup analysis of the use of Jakafi for the treatment of myelofibrosis and polycythemia vera, the difference was even more pronounced with a 59% reduction in the risk of thromboembolic events.
The nine studies in the thrombosis analysis included 1,872 patients, 950 of whom received JAKis and 922 of whom were in the control group. Studies that were included featured treatment with Jakafi and Ojjaara (momelotinib) among patients with polycythemia vera, myelofibrosis and essential thrombocythemia. The average follow-up time was 3.08 years in the JAKi group and 1.74 years in the control group.
However, there was no significant difference in rates of major adverse cardiovascular events or hypertension between the JAKi and control groups in the study.
“Our key findings are threefold: (1) JAKi treatment is associated with a significant reduction in thromboembolic event risk, primarily driven by studies of [Jakafi] in myelofibrosis and polycythemia vera,” Dunn and colleagues wrote. “(2) JAKi treatment is not associated with an increase in major adverse cardiovascular events in patients with MPNs. (3) The risk of hypertension is not significantly increased by JAKi treatment in patients with MPNs.”
“Treatment of Myeloproliferative Neoplasms With Janus Kinase Inhibitors: A Meta-Analysis of Cardiovascular Safety” by Roberta Dunn et al., eJHaem.
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