Su Victoria Ch, Greanya Erica D, Ensom Mary H H
Victoria CH Su BSc (Pharm) ACPR, PharmD student, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Erica D Greanya BSc (Pharm) ACPR PharmD, Pharmacy Specialist-Solid Organ Transplantation, Vancouver General Hospital, Vancouver; Clinical Assistant Professor, Faculty of Pharmaceutical Sciences, The University of British Columbia.
Ann Pharmacother. 2011 Feb;45(2):248-57. doi: 10.1345/aph.1P456.
To systematically evaluate the clinical consequences of mycophenolate dose reduction in renal transplant recipients on tacrolimus-based regimens.
PubMed (1949-July 2010), EMBASE (1980-July 2010), Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Web of Science were searched using the terms mycophenolate mofetil, tacrolimus, dose reduction, and kidney and/or renal transplant. References from publications identified were reviewed.
Studies reporting on rejection rate, allograft survival, or renal function were included and ranked according to the US Preventive Services Task Force classification; excluded were studies that were dose-finding or used cyclosporine only, involved patients on enteric-coated mycophenolate sodium or those with multiorgan transplant, or provided no information on concomitant immunosuppressants. Data extracted were study design, sample size, immunosuppression regimen, type of transplant, and allograft outcomes.
Of 13 studies included, 1 was level I evidence, 3 were level II-2, 6 were level II-3, and 3 were level III evidence. Three focused on tacrolimus-based regimens, whereas 7 included either cyclosporine or tacrolimus. The only prospective, randomized, multicenter trial demonstrated that early taper of mycophenolate dosage to 1 g/day can be utilized without increased risk of rejection, compared with late tapering, but the rejection rate was high (30-40%). Overall, we found conflicting evidence regarding the impact of mycophenolate dose reduction on rejection rate and allograft loss and that discontinuing mycophenolate led to an increased risk of graft loss as high as 8 fold. Allograft survival was lowest in patients with gastrointestinal complications and those in whom mycophenolate was discontinued, compared with patients with neither gastrointestinal complications nor mycophenolate discontinuation.
Weak evidence suggests that mycophenolate dose modifications, either reduction or discontinuation, may increase rejection rate and graft loss; however, this is more apparent in cyclosporine-based regimens. Prospective, well-designed trials are necessary to definitively determine the impact of dose reduction in renal transplant recipients on tacrolimus-based regimens.
系统评估在接受基于他克莫司方案治疗的肾移植受者中减少霉酚酸酯剂量的临床后果。
使用“霉酚酸酯”“他克莫司”“剂量减少”以及“肾脏和/或肾移植”等检索词，对PubMed（1949年 - 2010年7月）、EMBASE（1980年 - 2010年7月）、Cochrane系统评价数据库、国际药学文摘和科学引文索引进行检索。对已发表文献的参考文献进行了审查。
纳入报告排斥反应率、移植肾存活或肾功能的研究，并根据美国预防服务工作组分类进行排名；排除剂量探索性研究、仅使用环孢素的研究、涉及接受肠溶型霉酚酸钠治疗的患者或多器官移植患者的研究，以及未提供联合免疫抑制剂信息的研究。提取的数据包括研究设计、样本量、免疫抑制方案、移植类型和移植肾结局。
纳入的13项研究中，1项为I级证据，3项为II - 2级，6项为II - 3级，3项为III级证据。3项研究聚焦于基于他克莫司的方案，而7项研究包括环孢素或他克莫司。唯一一项前瞻性、随机、多中心试验表明，与延迟减量相比，霉酚酸酯剂量早期减至1克/天可在不增加排斥反应风险的情况下使用，但排斥反应率较高（30% - 40%）。总体而言，我们发现关于霉酚酸酯剂量减少对排斥反应率和移植肾丢失影响的证据相互矛盾，且停用霉酚酸酯会使移植肾丢失风险增加高达8倍。与既无胃肠道并发症又未停用霉酚酸酯的患者相比，有胃肠道并发症的患者和停用霉酚酸酯的患者移植肾存活率最低。
证据不足表明，霉酚酸酯剂量的调整，无论是减少还是停用，都可能增加排斥反应率和移植肾丢失；然而，在基于环孢素的方案中这种情况更为明显。需要进行前瞻性、设计良好的试验来明确确定肾移植受者中减少剂量对基于他克莫司方案的影响。
