背景:感染相关性溶血性尿毒综合征(IA-HUS),最常见的原因是感染了产志贺毒素的细菌,主要影响幼儿。它可能会严重危及生命,以及导致长期的肾脏和神经系统疾病。缺乏经证实疗效的特定治疗。由于补体旁路途径的激活发生在HUS中,单克隆C5抗体eculizumab经常在一次并发症的标签外使用,例如,癫痫发作,发生。Eculizumab非常昂贵并且具有感染风险。尚未系统地研究其在IA-HUS中的用途。这篇系统的综述旨在介绍,总结,并评估有关依库珠单抗给药对中长期结果的影响的所有现有数据(即,急性期后的结果,具有永久性字符)在IA-HUS中。
方法:PubMed,Embase,本研究系统搜索了WebofScience中报告依库珠单抗对IA-HUS中长期结局影响的研究.最后一次搜索发生在2022年3月2日。研究提供有关至少5名IA-HUS患者的中长期结果的原始数据,在急性疾病期间至少用一剂依库珠单抗治疗,包括在内。没有对患者群体施加其他限制。如果数据与其他研究有实质性重叠,则排除研究。或者未单独报告IA-HUS患者的结局.在非随机干预研究中,使用ROBINS-I工具评估研究质量的偏倚风险。数据进行描述性分析。
结果:共确定了2944项研究。其中,14项研究包括386例接受依库珠单抗治疗的患者符合纳入标准。所有研究都是观察性的。产生志贺毒素的大肠杆菌(STEC)在386例患者中的381例(98.7%)被确定为感染原,有效地限制了对STEC-HUS患者的数据解释。不可能在研究中汇集数据。没有研究报告依库珠单抗对任何中长期结果具有统计学意义的积极作用。大多数研究是,然而,由于混淆而存在严重的偏见风险,更严重的患者接受了依库珠单抗治疗.三项研究试图通过患者匹配来控制混杂因素,尽管由于匹配限制,残余偏倚仍然存在.
结论:目前的观察证据不允许任何关于依库珠单抗在IA-HUS中的影响的结论,考虑到严重的偏倚风险。随机临床试验的结果备受期待,因为迫切需要新的治疗策略来预防这些重症患者的长期发病。
■OSF注册管理机构,MSZY4,注册DOIhttps://doi.org/10.17605/OSF。IO/MSZY4。
BACKGROUND: Infection-associated hemolytic uremic syndrome (IA-HUS), most often due to infection with Shiga toxin-producing bacteria, mainly affects young children. It can be acutely life-threatening, as well as cause long-term kidney and neurological morbidity. Specific treatment with proven efficacy is lacking. Since activation of the alternative complement pathway occurs in HUS, the monoclonal C5 antibody eculizumab is often used off-label once complications, e.g., seizures, occur. Eculizumab is prohibitively expensive and carries risk of infection. Its utility in IA-HUS has not been systematically studied. This systematic
review aims to present, summarize, and evaluate all currently available data regarding the effect of eculizumab administration on medium- to long-term outcomes (i.e., outcomes after the acute phase, with a permanent character) in IA-HUS.
METHODS: PubMed, Embase, and Web of Science were systematically searched for studies reporting the impact of eculizumab on medium- to long-term outcomes in IA-HUS. The final search occurred on March 2, 2022. Studies providing original data regarding medium- to long-term outcomes in at least 5 patients with IA-HUS, treated with at least one dose of eculizumab during the acute illness, were included. No other restrictions were imposed regarding patient population. Studies were excluded if data overlapped substantially with other studies, or if outcomes of IA-HUS patients were not reported separately. Study quality was assessed using the ROBINS-I tool for risk of bias in non-randomized studies of interventions. Data were analyzed descriptively.
RESULTS: A total of 2944 studies were identified. Of these, 14 studies including 386 eculizumab-treated patients met inclusion criteria. All studies were observational. Shiga toxin-producing E. coli (STEC) was identified as the infectious agent in 381 of 386 patients (98.7%), effectively limiting the interpretation of the data to STEC-HUS patients. Pooling of data across studies was not possible. No study reported a statistically significant positive effect of eculizumab on any medium- to long-term outcome. Most studies were, however, subject to critical risk of bias due to confounding, as more severely ill patients received eculizumab. Three studies attempted to control for confounding through patient matching, although residual bias persisted due to matching limitations.
CONCLUSIONS: Current observational evidence does not permit any conclusion regarding the impact of eculizumab in IA-HUS given critical risk of bias. Results of randomized clinical trials are eagerly awaited, as new therapeutic strategies are urgently needed to prevent long-term morbidity in these severely ill patients.
UNASSIGNED: OSF Registries, MSZY4, Registration DOI https://doi.org/10.17605/OSF.IO/MSZY4 .