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Discontinuation of Eculizumab Maintenance Treatment for Atypical Hemolytic Uremic Syndrome: A Report of 10 Cases
发布于：2014年3月31日 文字：【大】【中】【小】
Am J Kidney Dis. 2014 Mar 19
Discontinuation of Eculizumab Maintenance Treatment for Atypical Hemolytic Uremic Syndrome: A Report of 10 Cases
Ardissino G, Testa S, Possenti I, Tel F, Paglialonga F, Salardi S, Tedeschi S, Belingheri M, Cugno M.
Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy, and as many as 70% of patients with aHUS have mutations in the genes encoding complement regulatory proteins. Eculizumab, a humanized recombinant monoclonal antibody targeting C5, has been used successfully in patients with aHUS since 2009. The standard maintenance treatment requires life-long eculizumab therapy, but the possibility of discontinuation has not yet been tested systematically. We report the safety of discontinuing eculizumab treatment in 10 patients who stopped treatment with the aim of minimizing the risk of adverse reactions, reducing the risk of meningitis, and improving quality of life while also reducing the considerable treatment costs. Disease activity was monitored closely at home by means of urine dipstick testing for hemoglobin. During the cumulative observation period of 95 months, 3 of the 10 patients experienced relapse within 6 weeks of discontinuation, but then immediately resumed treatment and completely recovered. Our experience supports the possibility of discontinuing eculizumab therapy with strict home monitoring for early signs of relapse in patients with aHUS who achieve stable remission.
Eculizumab成功用于治疗非典型溶血尿毒综合征（aHUS），但其停药后容易复发，目前在预后差者（如H因子基因突变）或移植后复发者是初步建议终身用药，但其费用极其昂贵。为了减少费用、减少感染（特别是脑膜炎球菌）、提高生活质量、减少免疫介导的药物反应（如产生抗eculizumab的自身抗体，从而使其疗效下降），希望是尽量能停药。
本文报道了10例aHUS在达到临床缓解（血小板、LDH和结合珠蛋白正常，无裂体细胞，肾功能正常或稳定）后、并充分告知其风险后、患者或家属选择停用eculizumab，停药前已平均使用eculizumab 5.6个月（0.4-14.2月）。此10例患者：1例H因子基因突变、1例H因子+I因子+THBD基因突变、3例I因子基因突变、1例MCP基因突变、1例CFHR3/R1缺失、1例H因子抗体阳性、1例H因子抗体阳性+CFRH3/R1缺失、1例H因子基因突变+CFRH3/R1缺失+H因子抗体阳性。嘱患者在家使用试纸密切监测尿中是否出现潜血，如潜血阳性，则及时就诊评估是否aHUS复发。中位停药时间9.3个月（0.9~22.7个月），3/10在停药6周内复发（复发的3例均为H因子基因突变或合并H因子基因突变），很快恢复使用eculizumab，血液系统和肾脏获得完全缓解。因此，本文提示在稳定缓解的aHUS患者、在密切监测有无复发迹象的情况下，同时考虑即使停用eculizumab后aHUS复发、再恢复使用eculizumab的效果也可以很好，可以考虑停用eculizumab。
http://www.ncbi.nlm.nih.gov/pubmed/24656451