Maruyama Shoichi, Ikeda Yoichiro, Kaname Shinya, Kato Noritoshi, Matsumoto Masanori, Ishikawa Yumiko, Shimono Akihiko, Miyakawa Yoshitaka, Nangaku Masaomi, Shibagaki Yugo, Okada Hirokazu
Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Division of Nephrology and Endocrinology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
J Nephrol. 2024 Nov;37(8):2181-2190. doi: 10.1007/s40620-024-01921-y. Epub 2024 May 29.
Eculizumab has been approved for atypical haemolytic-uraemic syndrome (aHUS) in Japan since 2013. Post-marketing surveillance enrolled patients with aHUS who received ≥ 1 dose of eculizumab to assess eculizumab safety and effectiveness.
We evaluated serious adverse events and effectiveness endpoints, i.e., haematologic normalization, a decrease of ≥ 25% in serum creatinine (sCr) levels, and complete thrombotic microangiopathy (TMA) response in adult patients with aHUS without other underlying diseases. In addition, the difference of baseline characteristics between patients who did and did not meet effectiveness endpoints was examined.
In this safety and effectiveness analysis, 79 adult patients were included; median age was 54.0 years, median treatment duration was 30 weeks. Total exposure time of eculizumab was 75.51 patient-years, and 94 serious adverse events were reported in 39 patients. No unexpected safety signals were identified in this population. Mean platelet count, lactate dehydrogenase and estimated glomerular filtration rate significantly improved after 7 days of treatment. Complete TMA response, haematologic normalization and the improvement of sCr levels were met by 35.3%, 40.4% and 51.3% of patients, respectively. Median treatment duration was shorter in patients who did not achieve complete TMA response (6 weeks) than in patients who did (114 weeks). Multivariate analysis suggested that the time from the most recent TMA episode to start of eculizumab treatment was negatively associated with kidney function improvement.
No unexpected safety signals of eculizumab were identified in Japanese patients with aHUS in a real-world setting. Renal outcomes were negatively associated with the time from the most recent TMA episode to the initiation of eculizumab treatment.
自2013年起，依库珠单抗在日本被批准用于治疗非典型溶血性尿毒症综合征（aHUS）。上市后监测纳入了接受≥1剂依库珠单抗治疗的aHUS患者，以评估依库珠单抗的安全性和有效性。
我们评估了严重不良事件和有效性终点，即血液学指标恢复正常、血清肌酐（sCr）水平降低≥25%，以及无其他基础疾病的成年aHUS患者完全缓解血栓性微血管病（TMA）。此外，还检查了达到和未达到有效性终点的患者基线特征差异。
在这项安全性和有效性分析中，纳入了79例成年患者；中位年龄为54.0岁，中位治疗持续时间为30周。依库珠单抗的总暴露时间为75.51患者年，39例患者报告了94起严重不良事件。在该人群中未发现意外的安全信号。治疗7天后，平均血小板计数、乳酸脱氢酶和估计肾小球滤过率显著改善。分别有35.3%、40.4%和51.3%的患者达到完全TMA缓解、血液学指标恢复正常和sCr水平改善。未达到完全TMA缓解的患者中位治疗持续时间（6周）短于达到完全缓解的患者（114周）。多因素分析表明，从最近一次TMA发作到开始依库珠单抗治疗的时间与肾功能改善呈负相关。
在真实世界环境中，日本aHUS患者未发现依库珠单抗意外的安全信号。肾脏结局与从最近一次TMA发作到开始依库珠单抗治疗的时间呈负相关。
