背景:补体介导的血栓性微血管病(CM-TMA),也称为非典型溶血性尿毒综合征(aHUS),是一种难以诊断的罕见疾病,具有严重的发病率和死亡率。抗C5单克隆抗体(aC5-mab)是标准治疗方法,但是大型研究和长期数据很少。这里,我们报告了我们单一机构的经验,以增加使用aC5-mab治疗的CM-TMA的知识。
方法:我们旨在评估aC5-mab在一项临床试验之外治疗的CM-TMA患者中的短期和长期效应。这是一项回顾性研究。我们纳入了所有诊断为CM-TMA并在我们机构接受aC5-mab治疗的患者。没有排除标准。终点包括完全TMA反应(CR),定义为肾病患者血液学参数正常化和血清肌酐(Cr)相对于基线改善≥25%。复发定义为失去先前达到的CR,发病率,不良事件,和生存。
结果:我们发现28例CM-TMA患者接受aC5-mab治疗。中位年龄为50岁。基线实验室:血小板计数93×109/L,血红蛋白8.6g/dL,乳酸脱氢酶1326U/L,血清Cr4.7mg/dL,和估计肾小球滤过率19毫升/分钟。1个个体接受肾脏替代疗法(RRT),10个个体在第一次给药aC5-mab的5天内开始RRT。与CM-TMA相关的遗传变异包括C3,CFB,CFH,CFHR1/3,CFI,和MCP。平均住院时间为24天。开始aC5-mab的中位时间为10天。16名受试者接受了RRT。出院时,27还活着14留在RRT上,4有CR。6个月时,23个病人还活着,18继续aC5-mab,8留在RRT上,9有CR。在过去6个月的最后一次随访中,20还活着,14继续aC5-mab,5留在RRT上,12有CR,1次失去随访。
结论:我们的研究提供了关于用aC5-mab治疗CM-TMA的长期结果的真实经验和见解。我们的研究结果证实,CM-TMA是一种侵袭性疾病,具有显著的发病率和死亡率,并证实aC5-mab是CM-TMA的相对有效疗法。我们的研究增加了实用性,对文学的真实体验,但未来的研究仍然势在必行。
BACKGROUND: Complement-mediated thrombotic microangiopathy (CM-TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult-to-diagnose rare disease that carries severe morbidity and mortality. Anti-C5 monoclonal antibodies (aC5-mab) are standard treatments, but large studies and long-term data are scarce. Here, we report our single institution experience to augment the knowledge of CM-TMA treated with aC5-mab therapy.
METHODS: We aimed to assess the short and long-term effects of aC5-mab in patients diagnosed with CM-TMA treated outside of a clinical
trial. This was a retrospective
study. We included all patients diagnosed with CM-TMA and treated with aC5-mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival.
RESULTS: We found 28 patients with CM-TMA treated with aC5-mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 109 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5-mab. Genetic variants associated with CM-TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5-mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5-mab, 8 remained on RRT, and 9 had a CR. At the last follow-up visit past 6 months, 20 were alive, 14 continued aC5-mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow-up.
CONCLUSIONS: Our
study provides real-world experience and insight into the long-term outcomes of CM-TMA treated with aC5-mab. Our findings validate that CM-TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5-mab is a relatively effective therapy for CM-TMA. Our
study adds practical, real-world experience to the literature, but future research remains imperative.