Reporting of Thromboembolic Events with JAK Inhibitors: Analysis of the FAERS Database 2010–2019 (Drug Safety)

Abstract Introduction A potentially elevated risk for pulmonary thrombosis with Janus kinase inhibitors (JAKinibs) was identified, as well as an increased risk for portal vein thrombosis, in ruxolitinib patients. Consequently, the objective of this investigation was to repeat a comprehensive analysis of the US FDA`s Adverse Event Reporting System (FAERS) database to assess postmarketing reporting rates of thromboembolic events (TEs) in patients treated with JAKinibs. Methods FAERS data (1 January 2010 to 30 September 2019) were searched for reports of all FDA-approved JAKinibs across all indications. For each drug–adverse drug reaction (ADR) pair, the reporting odds ratio (ROR) [two-sided 95% confidence interval (CI)] and empirical Bayesian geometric mean (EBGM) [one-sided 95% lower bound] were calculated to detect drug–ADR pairs with higher-than-expected reporting rates within the FAERS. Significance was declared when both lower 95% CI bounds were > 1. Results Significantly elevated reporting rates of pulmonary thrombosis were evident with tofacitinib (ROR 2.36 [1.69–3.31]; EBGM 2.01 [1.53]), as was pulmonary embolism with baricitinib (ROR 12.23 [8.35–17.89]; EBGM 7.72 [3.82]) and portal vein thrombosis with ruxolitinib (ROR 4.16 [2.70–6.40]; EBGM 4.52 [3.11]). Deep vein thrombosis reports were increased with baricitinib (ROR 14.84 [9.64–22.84]; EBGM 9.49 [5.91]), as was thrombosis with ruxolitinib (ROR 1.40 [1.20–1.63]; EBGM 1.72 [1.52]). The relationship between the time of treatment initiation and event occurrence indicated that time to events occurred randomly. Conclusions This study found significant reporting rates for TEs in patients treated with JAKinibs across brands and indications, providing additional evidence that JAKinibs may be contraindicated in patients at risk of TEs.