Impact of everolimus-based immunosuppression on transplant rejection or death in lung transplant recipients using the United States Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: The off-label use of everolimus in lung transplant recipients (LTRs) has increased; however, its safety profile across different immunosuppressive regimens remains insufficiently characterized. This study explored potential safety signals associated with the addition of everolimus to established immunosuppressive regimens using real-world data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: A retrospective observational analysis of FAERS data was conducted. To reduce potential confounding from drug-drug interactions, paired comparisons were restricted to regimen pairs that differed only by the presence or absence of everolimus. Reporting odds ratios (RORs) and adjusted RORs (aRORs) were calculated for each regimen, using the corresponding non-everolimus regimen as the reference. Associations were examined for the composite outcome of transplant rejection or death.

RESULTS: The everolimus plus tacrolimus regimen showed lower reporting of the composite outcome compared with the tacrolimus regimen (ROR: 0.238 [95% confidence interval (CI): 0.073-0.782], p = 0.018; aROR: 0.258 [95% CI: 0.078-0.860], p = 0.027). For other regimens, including tacrolimus plus prednisone, cyclosporine, and cyclosporine plus prednisone plus mycophenolate mofetil, the addition of everolimus showed a consistent but non-significant trend toward lower reporting (all RORs <1 and aRORs <1).

CONCLUSIONS: Analysis of FAERS data identified a potential signal of lower reporting of transplant rejection or death associated with the addition of everolimus to certain immunosuppressive regimens in LTRs. These findings warrant cautious interpretation because of the inherent limitations of FAERS and require validation in prospective studies.