Lewis Tyler C, Hotchkis Perry, Wong Adrian, Lamaina Victoria, Fitzpatrick Emily, Stiefel Avital, Ohanian Juliana, Schnier Joseph R, Lesko Melissa, Rudym Darya, Natalini Jake G, Angel Luis F
Transplant Institute, NYU Langone Health, New York, New York, USA.
Department of Pharmacy, NYU Langone Health, New York, New York, USA.
Clin Transplant. 2025 May;39(5):e70159. doi: 10.1111/ctr.70159.
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. Trial Registration: ClinicalTrials.gov identifier: NCT04420195.
他克莫司在预防肺移植术后同种异体移植物排斥反应和延长生存期方面非常有效。然而，不稳定的药代动力学可能会限制其疗效，并更容易导致更大的不良反应。我们对肺移植受者进行了一项前瞻性、开放标签试验，这些受者在早期（30天内）转换为长效他克莫司（LCP他克莫司，LCPT，n = 40），并将第一年的结果与继续使用速释他克莫司（IRT，n = 24）的历史对照组进行比较。受试者从IRT以1:1的比例转换为LCPT。LCPT的第一剂与IRT的最后一剂早晨剂量重叠。转换为LCPT的中位时间为17.5 [四分位间距12 - 25]天。14天时的转换剂量比为1.0毫克:毫克 [四分位间距0.75 - 1.50]。在1年时，LCPT组和IRT组在经活检证实的（12.5%对25.0%，p = 0.30）或临床治疗的（20.0%对25.0%，p = 0.64）急性细胞排斥反应发生率方面没有差异。然而，IRT队列中任何经活检证实的排斥反应的严重程度显著更高（27.5%对54.2%，p = 0.03）。虽然未达到统计学显著性，但新发供体特异性抗体在LCPT组中更常见（20.0%对4.2%，p = 0.14）。尽管如此，抗体介导的排斥反应发生率（7.5%对0.0%，p = 0.29）和早期慢性肺同种异体移植物功能障碍发生率（7.5%对9.1%，p = 1.00）相似。1年时4期或更严重的慢性肾病发生率相似（7.5%对12.5%，p = 0.66）。总之，在一组肺移植受者中，早期转换为LCPT是可行的，并且与IRT同样有效。试验注册：ClinicalTrials.gov标识符：NCT04420195。
