Analysis of Spontaneous Postmarket Case Reports Submitted to the FDA Regarding Thromboembolic Adverse Events and JAK Inhibitors
Thromboembolic-related adverse events (AEs) were, in general, not considered a class-wide safety concern after analysis of tofacitinib (TOF) and ruxolitinib (RUX) clinical data, though pulmonary thrombosis is considered a potential class-wide safety issue and portal vein thrombosis was considered a potential safety issue for RUX.
During analysis of baricitinib (BARI) clinical trial data, the FDA expressed concerns regarding thromboembolic events. Following this, the CHMP have recently added a precaution to the BARI label, for patients with a high risk of deep vein thrombosis (DVT) and pulmonary embolisms (PE). This safety review analysed the thromboembolic-related AEs to determine whether similar safety concerns should be associated with the FDA-approved drugs, TOF
FAERS, the FDA’s adverse event reporting system, was used to obtain safety data for TOF, TOF extended release (XR) and RUX. Cases reported in FAERS were included in analysis if the drug was listed as the primary suspect causing the AE. Analysis involved calculating reporting odds ratios, to note trends and significant differences.
Pulmonary thrombosis (PT), PE, DVT and thrombosis events were reported for all drugs; with PT identified as a potential safety risk for both TOF and RUX since 2016. Portal vein thrombosis (PVT) events were only reported for patients given RUX and in 2015, PVT was identified as a potential safety risk for patients given RUX.
With current data, thromboembolic-related AEs are not considered a class-wide safety issue, however, PT is considered a potential class-wide safety issue and PVT was considered a potential safety issue for RUX. To date, no event has been added to the FDA-approved label for any compounds within the class.