最新动态
A systematic review of eculizumab for atypical haemolytic uraemic syndrome (aHUS)
发布于：2013年11月11日 文字：【大】【中】【小】
A systematic review of eculizumab for atypical haemolytic uraemic syndrome (aHUS)
BMJ Open. 2013 Nov 4
OBJECTIVE: To determine the efficacy and safety of eculizumab for patients with atypical haemolytic uraemic syndrome (aHUS), compared with current treatment options.
DESIGN: A systematic review was performed according to the general principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. All study designs were included, except case histories.
PARTICIPANTS:All patients diagnosed with aHUS were included; no age restrictions were used.
INTERVENTIONS: Eculizumab compared with current treatment options.
IDENTIFICATION OF STUDIES: 12 databases were searched. Additional searches were performed through the Food and Drug Administration (FDA) and the Electronic Medicines Compendium websites, Google internet searches and contacting clinical experts. Reference lists of relevant articles were checked for additional studies.
RESULTS: 2 small, uncontrolled prospective multinational, multicentre studies and one small uncontrolled multinational, multicentre retrospective study were included. No meta-analyses were performed. Compared with baseline measures, thrombotic microangiopathy event-free status was achieved in 84% of patients in the prospective studies. Adverse events, as documented by enrolling investigators were frequent, with upper-respiratory tract infection affecting a third of patients. No deaths or episodes of meningitis or meningococcal septicaemia occurred in the prospective studies. Results of the study extension phases up to 114 weeks indicate that the benefits of the treatment are sustained.
CONCLUSIONS: Eculizumab is clinically effective for the treatment of aHUS. Further research is needed to evaluate eculizumab, ideally using patient-related clinical outcomes. If randomised studies are not feasible, study investigators should ensure that the threat of bias is minimised in future studies of eculizumab with respect to the reporting of patient recruitment and selection.
aHUS发病与补体旁路调节缺陷相关，包括H因子、I因子、MCP、THBD及C3、B因子基因突变，或抗H因子自身抗体。aHUS既往治疗以血浆置换/血浆输注为主，约60% aHUS血浆置换有效；然而，特别是H因子抗体阳性者，停止血浆置换后很容易复发，加用免疫抑制剂复发率会明显减少，但免疫抑制剂也未统一，霉酚酸酯、环磷酰胺、CD20单抗均有报道；血浆置换也存在其相关并发症，特别是儿童操作更困难。aHUS发展至ESRD后肾移植复发率也很高。最新的研究表明，Eculizumab对于aHUS有显著疗效，但目前无RCT；本文总结了至目前为止关于eculizumab的临床研究（个例报道除外），其包括3个前瞻性、非对照、多中心研究（因aHUS为罕见病，病例数少，做RCT困难；而且aHUS死亡率和ESRD发生率高，eculizumab在aHUS中已经发现有明显疗效，再做RCT伦理难通过），与用eculizumab前的基线资料相比，用eculizumab后随访至26周，80-88%患者无TMA相关事件，eGFR平均改善5-20ml/min/1.73m2，生活质量也明显改善，而且随访至114周时仍维持明显效果，无新发需要透析患者，无死亡或脑膜炎等严重并发症报道；而既往单用血浆置换治疗时，随访1年，0.8%死亡，46%发展至ESRD；提示eculizumab效果明显优于血浆置换；但目前eculizumab在aHUS无对照研究，所以对于像MCP基因突变可能出现自发缓解者其作用不清，而且明显受到报道、发表偏移误差的影响，