Kwiatkowski Matthew, Welch Patrick, McComb Jennifer, Shepler Brian
Purdue University College of Pharmacy, West Lafayette, IN, USA.
Lutheran Hospital, Fort Wayne, IN, USA.
J Pharm Technol. 2014 Feb;30(1):31-38. doi: 10.1177/8755122513507430. Epub 2013 Nov 5.
: To systematically review the existing literature concerning the utilization of bortezomib and eculizumab to determine if there is enough evidence to warrant their routine use in desensitization protocols for high-risk transplant candidates. : PubMed, Google Scholar, and ClinicalTrials.gov were searched using the terms bortezomib, eculizumab, desensitization, transplant, highly-sensitized, pre-sensitized, and antibody-mediated rejection (AMR). The articles included were published between January 2009 and August 2012. : All English-language articles involving human subjects were assessed for inclusion. The search included articles evaluating the use of these agents in desensitization and the prevention of AMR, but excluded articles investigating these drugs in the treatment of established AMR. : Highly sensitized transplant candidates are at an increased risk of developing AMR after transplant; desensitization potentially reduces this risk. The addition of bortezomib and eculizumab to current desensitization protocols may enhance outcomes. The bortezomib search produced 3 efficacy trials, 1 safety trial, 2 in-progress trials, 14 patient cases from 8 published case reports, and 3 efficacy study abstracts. : Much of the available literature assessing the efficacy of bortezomib and eculizumab for use in desensitization exists as restricted clinical trials and incomplete case reports. Bortezomib and eculizumab appear to be potentially effective additions to current desensitization protocols. However, we are unable to determine at this time whether these agents improve the most clinically relevant outcome of successful transplantation. Further well-designed clinical trials are needed to determine their true clinical efficacy in highly sensitized transplant candidates.
系统回顾有关硼替佐米和依库珠单抗应用的现有文献,以确定是否有足够证据支持其在高风险移植受者脱敏方案中的常规使用。在PubMed、谷歌学术和ClinicalTrials.gov中检索,检索词为硼替佐米、依库珠单抗、脱敏、移植、高敏、预致敏和抗体介导的排斥反应(AMR)。纳入的文章发表于2009年1月至2012年8月之间。评估所有涉及人类受试者的英文文章是否纳入。检索包括评估这些药物在脱敏和预防AMR中的应用的文章,但排除了研究这些药物治疗已确诊AMR的文章。高敏移植受者移植后发生AMR的风险增加;脱敏可能降低这种风险。在当前脱敏方案中添加硼替佐米和依库珠单抗可能会改善结果。硼替佐米的检索产生了3项疗效试验、1项安全性试验、2项正在进行的试验、来自8篇已发表病例报告的14例患者病例以及3篇疗效研究摘要。评估硼替佐米和依库珠单抗在脱敏中应用疗效的现有文献大多为受限的临床试验和不完整的病例报告。硼替佐米和依库珠单抗似乎可能是当前脱敏方案中有效的添加药物。然而,我们目前无法确定这些药物是否能改善成功移植这一最具临床相关性的结果。需要进一步设计良好的临床试验来确定它们在高敏移植受者中的真正临床疗效。