Thrombotic Microangiopathy Associated with Calcineurin Inhibitors: A Real-World Analysis of Postmarketing Surveillance Data.

Purpose: Calcineurin inhibitors (CNIs) are currently the first-line drugs for preventing and treating post-transplant rejection in organ transplant recipients. However, these drugs, especially tacrolimus, have the potential to induce thrombotic microangiopathy (TMA), a rare but potentially fatal complication that can develop following transplantation. This condition has garnered considerable attention within the medical community. Consequently, the study conducted an observational retrospective pharmacovigilance study to investigate the risk signal of thrombotic microangiopathy associated with CNIs.

Methods: A retrospective pharmacovigilance study was conducted to investigate the relationship between CNIs and TMA using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed to evaluate risk signals.

Findings: A total of 1019 cases of CNIs-associated TMA were identified, with 785 cases attributed to tacrolimus and 234 cases to cyclosporine A. Overall, the incidence of CNIs related TMA was higher compared to the entire database (ROR = 29.76 [27.84-31.82], IC = 4.64 [4.55-4.74]). A stronger signal was observed for tacrolimus-associated TMA compared to cyclosporine A (ROR = 3.72 [3.20-4.23], IC = 0.63 [0.50-0.77]). Additionally, residing in the Americas may be a protective factor against mortality in tacrolimus-related TMA, while for cyclosporine A-related TMA, patients from Asia and female patients have a significantly higher risk of death.

Implications: Clinician awareness of CNIs-associated TMA needs to be heightened, particularly with tacrolimus. Special attention should be given to patients' geographic regions and gender differences.