Venous Thromboembolism in Patients Treated with Everolimus: Insightsfrom a Case Series and the French Pharmacovigilance Database

Introduction/Objective: Kidney transplantation is a vital therapeutic option for individuals with end-stage renal disease. Among the various immunosuppressive agents available, everolimus, a selective inhibitor of the mammalian target of rapamycin, is widely used. While previous studies have reported an increased risk of venous thromboembolism (VTE) in heart and lung transplant recipients treated with everolimus, its impact in kidney transplant patients remains less explored. This study aimed to investigate the association between everolimus and VTE in renal transplant recipients. Methods: This study is a retrospective observational analysis combining a single-center case series of kidney transplant recipients and a review of cases retrieved from the French National Pharmacovigilance Database. Results: From February 2017 to February 2022, in our center, 5 VTE occurred in five kidney transplant patients treated with everolimus. Among them, 3 patients had recurrent VTE. The median time between everolimus initiation and VTE onset was 11 months IQR 3.8-15.0. Everolimus was discontinued in one patient (20.0%) following the VTE event. From the French pharmacovigilance database, 16 additional cases of VTE associated with everolimus in the context of organ transplantation were identified. Among these, 12 (75.0%) patients were male, with a median age of 63 years IQR 56.5-69.0. Transplanted organs included heart (43.8%), lung (18.8%), and kidney (18.8%). Pulmonary embolism was the most common presentation, occurring in 11 (68.8%) patients, while 2 (12.5%) patients had isolated lower-limb DVT. Thrombosis at unusual sites was reported in three cases: one upper-limb DVT, one jugular vein thrombosis, and one right ventricular intracardiac thrombus. The median time to VTE onset after everolimus initiation was 24 months IQR 7.5-42.0. Everolimus therapy was continued in 13 (81.2%) patients, with dose reduction in 2 (12.5%) and discontinuation in 3 (18.9%). Discussion: Everolimus may increase the risk of VTE in kidney transplant recipients. This risk appears to be higher in patients with a prior history of VTE before transplantation and during the first year following everolimus initiation. Conclusion: Our findings suggest that everolimus may increase the risk of VTE in kidney transplant recipients. Further studies are needed to confirm this association and to evaluate the benefit-risk profile of everolimus compared with other immunosuppressive therapies in renal transplant patients.