Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study
Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study
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DOI：
10.1182/blood.2020009280
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发表时间：
2021-05-06
期刊：
影响因子：
20.3
通讯作者：
Fremeaux-Bacchi, Veronique
中科院分区：
文献类型：
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作者：
Fakhouri, Fadi;Fila, Marc;Fremeaux-Bacchi, Veronique
非典型溶血性尿毒症综合征(AHUS)患者接受eculizumab治疗的最佳时间仍不明确。我们进行了一项前瞻性的全国性多中心开放标签研究，以评估患有急性HUS的儿童和成人停止使用eculizumab。55名患者(包括19名儿童)停用eculizumab(平均疗程16.5个月)。28例患者(51%)存在罕见的补体基因变异，主要发生在MCP(n=12；22%)、CFH(n=6；11%)和CFI(n=6；10%)。在Eulizumab停药时，17例(30%)和4例(7%)患者分别为3期和4期慢性肾脏疾病。在随访期间，13名患者(23%；6名儿童和7名成人)经历了AHUS复发。在多变量分析中，女性和补体基因中罕见变异的存在与aHUS复发的风险增加有关，而在以前的急性aHUS发作期间是否需要透析则不相关。此外，通过对数等级检验和多变量分析，在所有患者和具有补体基因罕见变异的携带者亚组中，停用eculizumab时血浆sC5b-9水平的升高与aHUS复发的风险更高。在全部重新启动eculizumab的13名复发患者中，11名恢复了基线肾功能，2名先前存在的慢性肾脏疾病恶化，包括1名进展为终末期肾病的患者。在aHUS患者中基于补体遗传学的eculizumab停用策略是合理和安全的。它改善了相当大比例的aHUS患者的管理和生活质量，同时降低了治疗成本。
The optimal duration of eculizumab treatment in patients with atypical hemolytic uremic syndrome (aHUS) remains poorly defined. We conducted a prospective national multi-center open-label study to assess eculizumab discontinuation in children and adults with aHUS. Fifty-five patients (including 19 children) discontinued eculizumab (mean treatment duration, 16.5 months). Twenty-eight patients (51%) had rare variants in complement genes, mostly in MCP (n = 12; 22%), CFH (n = 6; 11%), and CFI (n = 6; 10%). At eculizumab discontinuation, 17 (30%) and 4 patients (7%) had stage 3 and 4 chronic kidney disease, respectively. During follow-up, 13 patients (23%; 6 children and 7 adults) experienced aHUS relapse. In multivariable analysis, female sex and presence of a rare variant in a complement gene were associated with an increased risk of aHUS relapse, whereas requirement for dialysis during a previous episode of acute aHUS was not. In addition, increased sC5b-9 plasma level at eculizumab discontinuation was associated with a higher risk of aHUS relapse in all patients and in the subset of carriers with a complement gene rare variant, both by log-rank test and in multivariable analysis. Of the 13 relapsing patients, all of whom restarted eculizumab, 11 regained their baseline renal function and 2 had a worsening of their preexisting chronic kidney disease, including 1 patient who progressed to end-stage renal disease. A strategy of eculizumab discontinuation in aHUS patients based on complement genetics is reasonable and safe. It improves the management and quality of life of a sizeable proportion of aHUS patients while reducing the cost of treatment.