Cardiovascular-Related Mortality Risk in Primary Myelofibrosis in Pre-Ruxolitinib and Ruxolitinib Eras

Background Ruxolitinib, a Janus Kinase inhibitor, was approved in 2011 for the treatment of primary myelofibrosis (PMF) and has shown improved survival since its introduction. However, there are reports of possible cardiotoxicity linked to the medication. 1,2 Previous studies have shown that cardiovascular disease (CVD) was the third most common cause of death in PMF. 3 Given that patients with PMF may need therapy for several years, the cardiovascular safety profile of ruxolitinib has been the subject of increased scrutiny. Our goal was to compare the cardiovascular-related mortality (CVM) risk in patients with PMF in the pre-ruxolitinib (pre-Rux) and ruxolitinib (Rux) eras. Methods Using the Surveillance, Epidemiology, and End-result (SEER) Research Plus Data, 17 Registries and Multiple Primary Standardized Incidence Ratio (MP-SIR) registries (2000 - 2020), a retrospective study of patients diagnosed with PMF between 2003 and 2019 was conducted. This period was split into the pre-Rux (2003-2010) and post-approval Rux eras (2012-2019) and compared the standard mortality ratios (SMRs) of CVD in both periods. SMR was expressed as the ratio of cardiovascular deaths observed in PMF to those expected in the general population. Descriptive statistics (frequencies) were compared with Chi-square. The Kaplan-Meier method was used to estimate cumulative relative survival (CRS), and the sub-distribution hazard model for competing risk analysis was used to predict CVM; the significance test was set at