Tyler C. Lewis, Perry Hotchkis, Adrian Wong, Victoria Lamaina, Emily Fitzpatrick, Avital Stiefel, Juliana Ohanian, Joseph R. Schnier, Melissa Lesko, Darya Rudym, Jake G. Natalini, Luis F. Angel
{"title":"肺移植受者早期改用lcp -他克莫司（ENVARSUS XR）与速释他克莫司的比较","authors":"Tyler C. Lewis, Perry Hotchkis, Adrian Wong, Victoria Lamaina, Emily Fitzpatrick, Avital Stiefel, Juliana Ohanian, Joseph R. Schnier, Melissa Lesko, Darya Rudym, Jake G. Natalini, Luis F. Angel","doi":"10.1111/ctr.70159","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Tacrolimus is highly effective at preventing allograft rejection and prolonging survival after lung transplantation. However, erratic pharmacokinetics may limit efficacy and predispose to greater adverse effects. We conducted a prospective, open-label trial of lung transplant recipients who underwent early conversion (within 30 days) to LCP tacrolimus (LCPT, <i>n</i> = 40) and compared first-year outcomes to an historical control of patients who remained on immediate-release tacrolimus (IRT, <i>n</i> = 24). Subjects were converted 1:1 from IRT to LCPT. The first dose of LCPT overlapped with the last morning dose of IRT. Conversion to LCPT occurred at a median of 17.5 [IQR 12–25] days. The conversion dose ratio was 1.0 mg:mg [IQR 0.75–1.50] at 14 days. At 1 year, there were no differences between LCPT and IRT in the incidence of biopsy-proven (12.5% vs. 25.0%, <i>p</i> = 0.30) or clinically treated (20.0% vs. 25.0%, <i>p</i> = 0.64) acute cellular rejection. However, the severity of any biopsy-proven rejection was significantly higher in the IRT cohort (27.5% vs. 54.2%, <i>p</i> = 0.03). Although not achieving statistical significance, de novo donor-specific antibodies were more commonly observed in the LCPT group (20.0% vs. 4.2%, <i>p</i> = 0.14). Despite this, the incidence of antibody-mediated rejection (7.5% vs. 0.0%, <i>p</i> = 0.29) and early-onset chronic lung allograft dysfunction (7.5% vs. 9.1%, <i>p</i> = 1.00) were similar. The incidence of chronic kidney disease stage 4 or greater at 1-year was similar (7.5% vs. 12.5%, <i>p</i> = 0.66). In conclusion, early conversion to LCPT was feasible and similarly efficacious to IRT in a cohort of lung transplant recipients.</p>\n <p><b>Trial Registration</b>: ClinicalTrials.gov identifier: NCT04420195</p>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 5","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Comparison of Early Conversion to LCP-Tacrolimus (ENVARSUS XR) to Immediate-Release Tacrolimus in Lung Transplant Recipients\",\"authors\":\"Tyler C. Lewis, Perry Hotchkis, Adrian Wong, Victoria Lamaina, Emily Fitzpatrick, Avital Stiefel, Juliana Ohanian, Joseph R. Schnier, Melissa Lesko, Darya Rudym, Jake G. Natalini, Luis F. Angel\",\"doi\":\"10.1111/ctr.70159\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Tacrolimus is highly effective at preventing allograft rejection and prolonging survival after lung transplantation. However, erratic pharmacokinetics may limit efficacy and predispose to greater adverse effects. We conducted a prospective, open-label trial of lung transplant recipients who underwent early conversion (within 30 days) to LCP tacrolimus (LCPT, <i>n</i> = 40) and compared first-year outcomes to an historical control of patients who remained on immediate-release tacrolimus (IRT, <i>n</i> = 24). Subjects were converted 1:1 from IRT to LCPT. The first dose of LCPT overlapped with the last morning dose of IRT. Conversion to LCPT occurred at a median of 17.5 [IQR 12–25] days. The conversion dose ratio was 1.0 mg:mg [IQR 0.75–1.50] at 14 days. At 1 year, there were no differences between LCPT and IRT in the incidence of biopsy-proven (12.5% vs. 25.0%, <i>p</i> = 0.30) or clinically treated (20.0% vs. 25.0%, <i>p</i> = 0.64) acute cellular rejection. However, the severity of any biopsy-proven rejection was significantly higher in the IRT cohort (27.5% vs. 54.2%, <i>p</i> = 0.03). Although not achieving statistical significance, de novo donor-specific antibodies were more commonly observed in the LCPT group (20.0% vs. 4.2%, <i>p</i> = 0.14). Despite this, the incidence of antibody-mediated rejection (7.5% vs. 0.0%, <i>p</i> = 0.29) and early-onset chronic lung allograft dysfunction (7.5% vs. 9.1%, <i>p</i> = 1.00) were similar. The incidence of chronic kidney disease stage 4 or greater at 1-year was similar (7.5% vs. 12.5%, <i>p</i> = 0.66). In conclusion, early conversion to LCPT was feasible and similarly efficacious to IRT in a cohort of lung transplant recipients.</p>\\n <p><b>Trial Registration</b>: ClinicalTrials.gov identifier: NCT04420195</p>\\n </div>\",\"PeriodicalId\":10467,\"journal\":{\"name\":\"Clinical Transplantation\",\"volume\":\"39 5\",\"pages\":\"\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-04-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Transplantation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/ctr.70159\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"SURGERY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Transplantation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/ctr.70159","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}
引用次数: 0
摘要
他克莫司在预防同种异体移植排斥反应和延长肺移植术后存活方面具有很高的疗效。然而，不稳定的药代动力学可能会限制疗效，并容易产生更大的副作用。我们对早期（30天内）改用LCP他克莫司（LCPT, n = 40）的肺移植受体进行了一项前瞻性、开放标签试验，并将第一年的结果与继续使用速释他克莫司（IRT, n = 24）的历史对照组进行了比较。受试者以1:1的比例从IRT转为LCPT。第一次LCPT剂量与最后一次IRT剂量重叠。转为LCPT的中位时间为17.5 [IQR 12-25]天。第14天转换剂量比为1.0 mg:mg [IQR 0.75-1.50]。1年后，LCPT和IRT在活检证实的急性细胞排斥发生率（12.5% vs. 25.0%, p = 0.30）或临床治疗的急性细胞排斥发生率（20.0% vs. 25.0%, p = 0.64）方面没有差异。然而，任何活检证实的排斥反应的严重程度在IRT队列中明显更高（27.5%比54.2%,p = 0.03）。虽然没有统计学意义，但在LCPT组中，新生供体特异性抗体更常见（20.0% vs. 4.2%, p = 0.14）。尽管如此，抗体介导的排斥反应（7.5% vs. 0.0%, p = 0.29）和早发性慢性同种异体肺移植功能障碍（7.5% vs. 9.1%, p = 1.00）的发生率相似。1年慢性肾脏疾病4期或以上的发病率相似（7.5% vs. 12.5%, p = 0.66）。总之，在肺移植受者队列中，早期转化为LCPT是可行的，并且与IRT相似有效。试验注册：ClinicalTrials.gov标识符：NCT04420195
Comparison of Early Conversion to LCP-Tacrolimus (ENVARSUS XR) to Immediate-Release Tacrolimus in Lung Transplant Recipients
Tacrolimus is highly effective at preventing allograft rejection and prolonging survival after lung transplantation. However, erratic pharmacokinetics may limit efficacy and predispose to greater adverse effects. We conducted a prospective, open-label trial of lung transplant recipients who underwent early conversion (within 30 days) to LCP tacrolimus (LCPT, n = 40) and compared first-year outcomes to an historical control of patients who remained on immediate-release tacrolimus (IRT, n = 24). Subjects were converted 1:1 from IRT to LCPT. The first dose of LCPT overlapped with the last morning dose of IRT. Conversion to LCPT occurred at a median of 17.5 [IQR 12–25] days. The conversion dose ratio was 1.0 mg:mg [IQR 0.75–1.50] at 14 days. At 1 year, there were no differences between LCPT and IRT in the incidence of biopsy-proven (12.5% vs. 25.0%, p = 0.30) or clinically treated (20.0% vs. 25.0%, p = 0.64) acute cellular rejection. However, the severity of any biopsy-proven rejection was significantly higher in the IRT cohort (27.5% vs. 54.2%, p = 0.03). Although not achieving statistical significance, de novo donor-specific antibodies were more commonly observed in the LCPT group (20.0% vs. 4.2%, p = 0.14). Despite this, the incidence of antibody-mediated rejection (7.5% vs. 0.0%, p = 0.29) and early-onset chronic lung allograft dysfunction (7.5% vs. 9.1%, p = 1.00) were similar. The incidence of chronic kidney disease stage 4 or greater at 1-year was similar (7.5% vs. 12.5%, p = 0.66). In conclusion, early conversion to LCPT was feasible and similarly efficacious to IRT in a cohort of lung transplant recipients.
期刊介绍：
Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored.
Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include:
Immunology and immunosuppression;
Patient preparation;
Social, ethical, and psychological issues;
Complications, short- and long-term results;
Artificial organs;
Donation and preservation of organ and tissue;
Translational studies;
Advances in tissue typing;
Updates on transplant pathology;.
Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries.
Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
