Efficacy and safety of everolimus with reduced tacrolimus versus standard tacrolimus in liver transplant recipients: A systematic review and meta-analysis of randomized controlled trials

IF 1.6 4区医学 Q4 IMMUNOLOGY

Transplant immunology Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI:10.1016/j.trim.2025.102317

Akash Kumar , Mateen Ahmad , Amna Hussain , Khadija Mohib , Muhammad Asjad Saleem , Muhammad Saad , Muhammad Ansab , Ram , Pinkey Kumari , Nisha Kumari

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引用次数: 0

Abstract

Background

Liver transplantation (LT) requires immunosuppression to prevent rejection while minimizing adverse effects. Tacrolimus (TAC) is standard but linked to nephrotoxicity and leukopenia. Everolimus (EVR) with reduced-dose TAC (rTAC) offers a potential alternative, potentially improving safety while preserving efficacy.

Objectives

To compare everolimus with reduced-dose tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) in liver transplant recipients, assessing composite efficacy as the primary outcome, with graft loss, peripheral edema, mortality and evaluating safety via incidence of adverse events.

Methods

PubMed, Cochrane Library, and ClinicalTrials.gov were systematically searched from inception until 1st March 2025. Randomized controlled trials (RCTs) comparing everolimus with reduced-dose tacrolimus (EVR + rTAC) versus standard tacrolimus (TAC) in liver transplant (LT) recipients were included. A random-effects model was used for meta-analysis to calculate pooled risk ratios with 95 % confidence intervals (CI).

Results

A total of seven studies encompassing 1853 liver transplant recipients (EVR + rTAC: 1167; sTAC: 1174) were included. EVR + rTAC significantly reduced the risk of treated biopsy-proven acute rejection (tBPAR) compared to sTAC (RR: 0.67; 95 % CI: 0.47–0.94; p = 0.02; I² = 1 %). Renal function, assessed by estimated glomerular filtration rate (eGFR), was significantly better in the EVR + rTAC group (MD: 8.41; 95 % CI: 2.37–14.44; p = 0.006; I² = 86 %). Additionally, EVR + rTAC was associated with a significantly higher risk of peripheral edema (RR: 1.56; 95 % CI: 1.25–1.95; p < 0.0001; I² = 0 %) and leukopenia (RR: 2.87; 95 % CI: 1.99–4.13; p < 0.00001; I² = 0 %).

No significant differences were observed between the EVR + rTAC and sTAC groups regarding the composite efficacy outcome (RR: 0.79; 95 % CI: 0.62–1.00; p = 0.05; I² = 0 %), graft loss (RR: 1.25; 95 % CI: 0.73–2.14; p = 0.41; I² = 0 %), mortality (RR: 1.30; 95 % CI: 0.87–1.96; p = 0.20; I² = 0 %), or the incidence of serious adverse events (RR: 1.03; 95 % CI: 0.94–1.12; p = 0.52; I² = 79 %). Furthermore, no significant differences were noted regarding diarrhea, abdominal pain, headache, or hypertension.

Conclusion

Everolimus with reduced-dose tacrolimus (EVR + rTAC) showed comparable efficacy to standard tacrolimus, with no significant differences in graft loss or mortality. It significantly reduced the risk of acute rejection and improved renal function (higher eGFR) but increased the risk of leukopenia and peripheral edema. Further studies are needed to optimize this renal-sparing regimen.

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依维莫司与减量他克莫司对比标准他克莫司在肝移植受者中的疗效和安全性：随机对照试验的系统评价和荟萃分析。

背景：肝移植（LT）需要免疫抑制来防止排斥反应，同时尽量减少不良反应。他克莫司（TAC）是标准的，但与肾毒性和白细胞减少有关。依维莫司（EVR）与减少剂量的TAC （rTAC）提供了一种潜在的替代方案，可能在保持疗效的同时提高安全性。目的：比较依维莫司与减少剂量他克莫司（EVR + rTAC）与标准他克莫司（sTAC）在肝移植受者中的疗效，评估综合疗效作为主要结局，包括移植物损失、外周水肿、死亡率，并通过不良事件发生率评估安全性。方法：系统检索PubMed、Cochrane Library和ClinicalTrials.gov，检索时间从建站到2025年3月1日。随机对照试验（rct）比较依维莫司与减少剂量他克莫司（EVR + rTAC）与标准他克莫司（TAC）在肝移植（LT）受者中的作用。采用随机效应模型进行meta分析，计算合并风险比，置信区间（CI）为95% %。结果：共纳入7项研究，包括1853名肝移植受者（EVR + rTAC: 1167; sTAC: 1174）。与sTAC相比，EVR + rTAC显著降低了经活检证实的急性排斥反应（tBPAR）的风险（RR: 0.67; 95 % CI: 0.47-0.94; p = 0.02;I2 = 1 %）。通过估算肾小球滤过率（eGFR）评估的肾功能，EVR + rTAC组明显更好（MD: 8.41; 95 % CI: 2.37-14.44; p = 0.006;I2 = 86 %）。此外,将 + rTAC与周边水肿的风险更高(RR: 1.56; 95 % CI: 1.25 - -1.95; p 2 = 0 %)和白血球减少症(RR: 2.87; 95 % CI: 1.99 - -4.13; p 2 = 0 %)。没有观察到显著差异之间的应答 + rTAC和sTAC组织关于复合功效的结果(RR: 0.79; 95 % CI: 0.62 - -1.00; p = 0.05;I2 = 0 %),贪污损失(RR: 1.25; 95 % CI: 0.73 - -2.14; p = 0.41;I2 = 0 %),死亡率(RR: 1.30; 95 % CI: 0.87 - -1.96; p = 0.20;I2 = 0 %),或严重不良事件的发生率(RR: 1.03; 95 % CI: 0.94 - -1.12; p = 0.52;I2 = 79 %)。此外，在腹泻、腹痛、头痛或高血压方面没有显著差异。结论：依维莫司联合减剂量他克莫司（EVR + rTAC）的疗效与标准他克莫司相当，移植物损失和死亡率无显著差异。它显著降低了急性排斥反应的风险，改善了肾功能（eGFR升高），但增加了白细胞减少和外周水肿的风险。需要进一步的研究来优化这种肾保护方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplant immunology 医学-免疫学

CiteScore

2.10

自引率

13.30%

发文量

198

审稿时长

48 days

期刊介绍： Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.