| アブストラクト | Background Simultaneous pancreas-kidney (SPK) transplantation is a key treatment option for patients with diabetes and end-stage renal disease, but intensive multidrug immunosuppression increases the risk of adverse events (AEs). Evidence guiding stepwise de-escalation of immunosuppressive regimens in this setting remains limited, as prospective studies are difficult to conduct due to the rarity and complexity of the procedure. Large postmarketing pharmacovigilance databases such as the United States Food and Drug Administration Adverse Event Reporting System (FAERS) provide an opportunity to evaluate the safety of immunosuppressive strategies in real‑world practice. Objectives To characterize exploratory AE reporting patterns across four post-transplant immunosuppressive regimens after SPK transplantation. Methods AE reports for SPK transplant recipients were retrieved from the FAERS database (2004Q1-2025Q2). Immunosuppressive exposure was classified into four regimen groups: tacrolimus, mycophenolate mofetil, prednisone, and basiliximab (TMPB); tacrolimus, mycophenolate mofetil, and prednisone (TMP); tacrolimus and mycophenolate mofetil (TM); and tacrolimus monotherapy (T). Reports involving additional immunosuppressive agents were excluded. Transplant rejection, infections, and other clinically relevant AEs were grouped into predefined categories, and serious AEs (SAEs) were identified according to regulatory criteria. Reporting proportions were calculated for each AE category, and reporting odds ratios (RORs) and adjusted RORs (aRORs) were estimated using the TMPB group as the reference, with adjustment for sex, age, and continent. A Bonferroni‑adjusted two‑sided significance level of 0.017 was applied to account for three primary between‑regimen comparisons. Results A total of 569 SPK recipients met the inclusion criteria (TMPB group, N = 59; TMP group, N = 231; TM group, N = 95; T group, N = 184). Reporting of transplant rejection was highest in the TMPB group and lower in the TMP, TM, and T groups; all three regimens had lower RORs and aRORs for rejection than TMPB. Infections were reported more frequently in the TMPB and TMP groups and less frequently in the TM and T groups, with lower adjusted odds in the TM and T groups versus TMPB. Reporting proportions for renal, pancreatic, gastrointestinal, hematologic disorders, and drug toxicity were broadly similar across regimens. SAEs were numerically more frequent in the T group than in the other regimens, but this difference did not meet the prespecified significance threshold. Analyses in kidney‑only transplant recipients yielded qualitatively similar trends. Conclusions Across four post-transplant immunosuppressive regimens, lower reporting of transplant rejection and infections was observed in the TM group; however, because regimen assignment likely reflects post-transplant phase and clinical stability, these patterns should be interpreted as exploratory reporting differences rather than comparative safety effects. Because spontaneous reporting data cannot adequately adjust for time-related confounding, these hypothesis-generating findings warrant prospective validation. |
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| 組織名 | Clinical Research Support Center, Mie University Hospital, Tsu, JPN.;Department of Pharmaceutical Sciences for Health Crisis Management, Faculty of;Pharmaceutical Sciences, Fukuoka University, Fukuoka, JPN.;Organ Transplantation Center, Mie University Hospital, Tsu, JPN. |
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