Ogura Toru, Shiraishi Chihiro
Clinical Research Support Center, Mie University Hospital, Tsu, JPN.
Department of Pharmacy, Mie University Hospital, Tsu, JPN.
Cureus. 2024 May 13;16(5):e60193. doi: 10.7759/cureus.60193. eCollection 2024 May.
Background Immunosuppressants are administered in various combinations to prevent immune-induced transplant rejection in patients with liver transplant, as each immunosuppressant acts on different cellular sites. However, the use of multiple immunosuppressants also increases the risk for adverse events. Therefore, it is desirable to reduce the types of immunosuppressants administered without increasing the incidence of transplant rejection. The effectiveness of prednisone avoidance has been suggested, although this was not based on statistical significance in many instances. To definitively establish the effectiveness of prednisone avoidance, a statistically significant difference from a prednisone-use group should be demonstrated. Additionally, the effectiveness of prednisone avoidance might vary depending on the combination of other immunosuppressants administered. It has therefore been considered necessary to investigate, for various immunosuppressant combinations, the administration patterns in which prednisone avoidance is effective. Objectives This study aimed to investigate the effectiveness of prednisone avoidance in patients with liver transplant and discuss the results based on statistically significant differences. Methods Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) were obtained. In studying immunosuppressant combinations, it was essential to control for confounding. Thus, the immunosuppressant combinations, excluding prednisone, were kept the same in the two groups being compared (prednisone-use and prednisone-avoidance groups). The large sample from FAERS allowed for those various immunosuppressant combinations to be compared. Comparisons of transplant rejection in the prednisone-use and prednisone-avoidance groups used the reporting odds ratio (ROR) and the adjusted ROR (aROR), which controlled for differences in patient background. Results With the prednisone-use groups being set as the reference, ROR and aROR were calculated for the prednisone-avoidance groups. Various immunosuppressant combinations were evaluated, and in four patterns - (1) the combination of prednisone and tacrolimus, (2) the combination of prednisone, cyclosporine, and tacrolimus, (3) the combination of prednisone, tacrolimus, and basiliximab, and (4) the combination of prednisone and everolimus) - both the ROR and the aROR for transplant rejection in the prednisone-avoidance group were significantly <1.000. Conclusions This study identified effective immunosuppressant combinations for prednisone avoidance that were not associated with increased transplant rejection. The evidence supporting the effectiveness of prednisone avoidance is strengthened when combined with results from previous studies.
免疫抑制剂通常以多种组合方式给药，以预防肝移植患者发生免疫诱导的移植排斥反应，因为每种免疫抑制剂作用于不同的细胞位点。然而，使用多种免疫抑制剂也会增加不良事件的风险。因此，希望在不增加移植排斥发生率的情况下减少免疫抑制剂的使用种类。尽管在许多情况下这并非基于统计学显著性，但已有人提出避免使用泼尼松的有效性。为了明确确定避免使用泼尼松的有效性，应证明与使用泼尼松的组存在统计学显著差异。此外，避免使用泼尼松的有效性可能因所使用的其他免疫抑制剂组合而异。因此，人们认为有必要针对各种免疫抑制剂组合，研究避免使用泼尼松有效的给药模式。
本研究旨在调查肝移植患者避免使用泼尼松的有效性，并基于统计学显著差异讨论结果。
获取了美国食品药品监督管理局不良事件报告系统（FAERS）的数据。在研究免疫抑制剂组合时，控制混杂因素至关重要。因此，在进行比较的两组（使用泼尼松组和避免使用泼尼松组）中，除泼尼松外的免疫抑制剂组合保持相同。FAERS的大样本使得可以对各种免疫抑制剂组合进行比较。使用报告比值比（ROR）和调整后的ROR（aROR）对使用泼尼松组和避免使用泼尼松组的移植排斥情况进行比较，后者控制了患者背景差异。
以使用泼尼松组作为参考，计算避免使用泼尼松组的ROR和aROR。对各种免疫抑制剂组合进行了评估，在四种模式下 - （1）泼尼松与他克莫司的组合，（2）泼尼松、环孢素和他克莫司的组合，（3）泼尼松、他克莫司和巴利昔单抗的组合，以及（4）泼尼松与依维莫司的组合 - 避免使用泼尼松组移植排斥的ROR和aROR均显著<1.000。
本研究确定了可有效避免使用泼尼松且不增加移植排斥风险的免疫抑制剂组合。将本研究结果与先前研究结果相结合，支持避免使用泼尼松有效性的证据得到了加强。
