Department of Pharmacy, University of California San Diego, La Jolla, CA, USA.
Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, CA, USA.
Clin Transplant. 2021 Apr;35(4):e14228. doi: 10.1111/ctr.14228. Epub 2021 Feb 2.
There are limited real-world data available regarding adverse events (AEs) of immunosuppressants. We utilized the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2018 to perform a retrospective database analysis. We analyzed AE reports due to the individual agents tacrolimus, sirolimus, or everolimus and compared reporting odds ratios of the mTOR inhibitors to tacrolimus. The mTOR inhibitors arm had 1282 reports with 4176 AEs, while the tacrolimus arm had a total of 7587 reports with 20 940 individual AEs. mTOR inhibitors had significantly higher incidences of cardiovascular (ROR 1.95, 95% CI 1.70, 2.23), dermatologic (ROR 1.34, 95% CI 1.04, 1.73), endocrine (ROR 1.52, 95% CI 1.26, 1.82), gastrointestinal (ROR 1.15, 95% CI 1.01, 1.30), infectious disease (ROR 1.35, 95% 1.20, 1.52), musculoskeletal (ROR 1.39, 95% CI 1.13, 1.70), pulmonary (ROR 3.46, 95% 2.97, 4.03), renal (ROR 1.27, 95% CI 1.10, 1.46), and vascular AEs (ROR 3.10, 95% CI 2.14, 4.49). Across every organ type, mTOR inhibitors had greater cardiovascular AEs compared to tacrolimus, specifically in arteriosclerosis, heart failure, hypotension, tachycardia, chest pain, edema, and pericardial disorders. mTOR inhibitors may be associated with higher cardiovascular AEs. Further investigation is required to determine the potential mechanism of this effect.
关于免疫抑制剂的不良事件（AE），目前可用的真实世界数据有限。我们利用 2004 年至 2018 年的 FDA 不良事件报告系统（FAERS）数据库进行了回顾性数据库分析。我们分析了由于个体药物他克莫司、西罗莫司或依维莫司引起的 AE 报告，并比较了 mTOR 抑制剂与他克莫司的报告比值比（ROR）。mTOR 抑制剂组有 1282 例报告和 4176 例 AE，而他克莫司组共有 7587 例报告和 20940 例 AE。mTOR 抑制剂的心血管（ROR 1.95，95%CI 1.70，2.23）、皮肤（ROR 1.34，95%CI 1.04，1.73）、内分泌（ROR 1.52，95%CI 1.26，1.82）、胃肠道（ROR 1.15，95%CI 1.01，1.30）、传染病（ROR 1.35，95%CI 1.20，1.52）、肌肉骨骼（ROR 1.39，95%CI 1.13，1.70）、肺部（ROR 3.46，95%CI 2.97，4.03）、肾脏（ROR 1.27，95%CI 1.10，1.46）和血管 AE（ROR 3.10，95%CI 2.14，4.49）的发生率显著更高。在每一种器官类型中，mTOR 抑制剂的心血管 AE 发生率都高于他克莫司，特别是在动脉硬化、心力衰竭、低血压、心动过速、胸痛、水肿和心包疾病方面。mTOR 抑制剂可能与更高的心血管 AE 相关。需要进一步研究以确定这种效应的潜在机制。
