BACKGROUND The ScanCLAD study reported a lower incidence of chronic lung allograft dysfunction (CLAD) with the use of once-daily tacrolimus vs twice-daily cyclosporine. Using the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant (TTX) Registry data, we evaluated the hypothesis that tacrolimus is superior to cyclosporine in real-world clinical practice. METHODS This study is a retrospective cohort study of adult lung transplant recipients in the ISHLT registry from January 1, 2000, to June 30, 2018, with known CLAD status. The primary exposure variable was patients' maintenance calcineurin inhibitor (CNI) regimen captured at posttransplant discharge. The primary outcome variables were time to CLAD development (with death/retransplantation analyzed as a competing risk) and allograft survival (i.e., time to death/retransplant). RESULTS Of the 57,403 adult lung transplant recipients in the registry, 22,222 had both CNI and CLAD data available. Of these, 19,698 (88.6%) received tacrolimus immediate release (IR), 2,477 (11.2%) received cyclosporine, and 47 (0.2%) received tacrolimus extended release (XR) for maintenance CNI. Receiving cyclosporine for maintenance immunosuppression (vs tacrolimus IR) was associated with an increased risk of developing CLAD (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.08-1.23, p < 0.001) and with an increased overall risk for death/retransplant (HR 1.16, 95% CI 1.09-1.23, p < 0.001). Receiving tacrolimus XR vs tacrolimus IR was not associated with differences in long-term posttransplant outcomes, although these analyses were limited by a small sample size. CONCLUSIONS Patients receiving cyclosporine vs tacrolimus IR for maintenance calcineurin inhibition had an increased risk of CLAD and decreased overall allograft survival in the ISHLT TTX registry.

中文翻译：

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他克莫司与环孢菌素对国际心肺移植学会登记处慢性肺同种异体移植物功能障碍发生率和同种异体移植物存活率的影响。


背景 ScanCLAD 研究报告称，与每日两次环孢菌素相比，使用每日一次他克莫司的慢性肺同种异体移植物功能障碍 （CLAD） 的发生率较低。使用国际心肺移植学会 （ISHLT） 胸腔器官移植 （TTX） 登记数据，我们评估了他克莫司在实际临床实践中优于环孢菌素的假设。方法 本研究是一项回顾性队列研究，对 2000 年 1 月 1 日至 2018 年 6 月 30 日期间 ISHLT 登记处中具有已知 CLAD 状态的成年肺移植受者进行研究。主要暴露变量是移植后出院时捕获的患者维持钙调磷酸酶抑制剂 （CNI） 方案。主要结局变量是 CLAD 发展的时间 （死亡/再移植作为竞争风险分析） 和同种异体移植物存活率 （即死亡/再移植的时间）。结果 在登记的 57,403 名成年肺移植受者中，有 22,222 名同时有 CNI 和 CLAD 数据。其中，19,698 例 （88.6%） 接受他克莫司速释剂 （IR），2,477 例 （11.2%） 接受环孢菌素，47 例 （0.2%） 接受他克莫司缓释剂 （XR） 维持 CNI。接受环孢素维持免疫抑制 （与他克莫司 IR 相比） 与发生 CLAD 的风险增加相关 （风险比 [HR] 1.16,95% 置信区间 [CI] 1.08-1.23，p < 0.001）和死亡/再移植的总体风险增加 （HR 1.16,95% CI 1.09-1.23，p < 0.001）。接受他克莫司 XR 与他克莫司 IR 与移植后长期结局的差异无关，尽管这些分析受到样本量小的限制。 结论 在 ISHLT TTX 登记处，接受环孢素与他克莫司 IR 维持钙调磷酸酶抑制的患者发生 CLAD 的风险增加，同种异体移植物总存活率降低。