Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data.
Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data.
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DOI：
10.1136/bmj.g6679
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发表时间：
2014-11-24
期刊：
影响因子：
--
通讯作者：
Fergusson DA
中科院分区：
文献类型：
--
作者：
Knoll GA;Kokolo MB;Mallick R;Beck A;Buenaventura CD;Ducharme R;Barsoum R;Bernasconi C;Blydt-Hansen TD;Ekberg H;Felipe CR;Firth J;Gallon L;Gelens M;Glotz D;Gossmann J;Guba M;Morsy AA;Salgo R;Scheuermann EH;Tedesco-Silva H;Vitko S;Watson C;Fergusson DA
目的探讨肾移植患者接受免疫抑制药物西罗莫司治疗后发生恶性肿瘤和死亡的风险。设计对个别患者数据进行系统回顾和荟萃分析。数据来源Medline、Embase和Cochrane中央对照试验登记从最初到2013年3月。合格的随机对照试验，比较肾移植或胰肾联合移植受者使用西罗莫司和不使用西罗莫司的免疫抑制方案，作者愿意提供患者个体水平的数据。两名审查员独立筛选可能符合条件的试验的标题/摘要和全文报告，以确定纳入的研究。所有符合条件的试验都报告了关于恶性肿瘤或生存的数据。结果检索出2365条独特引文。患者水平的数据来自21个随机试验的5876名患者。与对照组相比，西罗莫司与恶性肿瘤风险降低40%(调整后的风险比0.60，95%可信区间0.39至0.93)和非黑色素瘤皮肤癌风险降低56%(0.44，0.30至0.63)相关。最显著的效果出现在从已有的免疫抑制方案转为西罗莫斯的患者身上，结果是恶性肿瘤(0.34，0.28至0.41)、非黑色素瘤皮肤癌(0.32，0.24至0.42)和其他癌症(0.52，0.38至0.69)的风险降低。与对照组相比，西罗莫司与死亡风险增加相关(1.43，1.21至1.71)。结论西罗莫司与移植受者恶性肿瘤和非黑色素瘤皮肤癌的风险降低有关。这种益处在从已有的免疫抑制方案转换为西罗莫司的患者中最为明显。然而，考虑到死亡的风险，对于大多数肾移植患者来说，似乎不应该使用这种药物。需要进一步的研究来确定不同的人群，如癌症高危人群，是否可能受益于西罗莫司。
Objective To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus. Design Systematic review and meta-analysis of individual patient data. Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013. Eligibility Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival. Results The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. The most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls. Conclusions Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.
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