Department of Paediatric Nephrology, Great Ormond Street Hospital, London, UK.
Division of Pediatric Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Pediatr Nephrol. 2023 Apr;38(4):1075-1086. doi: 10.1007/s00467-022-05684-1. Epub 2022 Aug 1.
Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018-004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here.
Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7-20.5) months).
Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)).
Lumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1. A higher resolution version of the Graphical abstract is available as Supplementary information.
原发性高草酸尿症 1 型（PH1）是一种罕见的遗传性疾病，由于肝脏草酸过度生成，导致进行性肾脏损伤和全身草酸盐病。在为期 6 个月的 3 期、多中心、开放标签、单臂 ILLUMINATE-B 研究的主要分析期内，lumasiran 已显示出疗效和安全性，该研究纳入了 < 6 岁的 PH1 婴儿和儿童（ClinicalTrials.gov：NCT03905694（4/1/2019）；EudraCT：2018-004,014-17（10/12/2018））。本文报道了完成研究 ≥ 12 个月的患者在 ILLUMINATE-B 扩展期（EP）的结局。
在 6 个月主要分析期纳入的 18 例患者中，所有患者均进入 EP 并完成了 ≥ 6 个月的 lumasiran 治疗（总暴露中位数（范围）持续时间为 17.8（12.7-20.5）个月）。
先前报道，lumasiran 治疗可使第 6 个月时的尿草酸盐：肌酐比值降低 72%，第 12 个月时维持在 72%；在预先指定的体重亚组中，第 12 个月时的平均降幅分别为体重 < 10 kg、10 至 < 20 kg 和 ≥ 20 kg 的患者的 89%、68%和 71%。报道称，第 6 个月时血浆草酸盐水平从基线的平均降幅为 32%，第 12 个月时改善至 47%。还观察到肾钙沉着症分级的进一步改善，肾结石发生率仍较低。最常见的与 lumasiran 相关的不良事件为轻度、短暂的注射部位反应（3 例（17%））。
在 PH1 的婴儿和幼儿中，lumasiran 治疗在所有体重亚组中均可在第 12 个月时持续降低尿和血浆草酸盐，安全性可接受。可提供高分辨率版本的图表摘要作为补充信息。
