DAILY-LUMA队列中卢马西拉两年使用的真实世界数据。
Real-Life Data of 2-Year Lumasiran Use in the DAILY-LUMA Cohort.
作者信息
Sellier-Leclerc Anne-Laure, Cloarec Melissa, Knebelmann Bertrand, Allard Lise, Boyer Olivia, Cloarec Sylvie, Dossier Claire, Le Quintrec Moglie, Nobili François, Stehlé Thomas, Vrillon Isabelle, Burtey Stéphane, Cornec-Le Gall Emilie, Courbebaisse Marie, Frouget Thierry, Garnier Arnaud, Krummel Thierry, Lemoine Sandrine, Monet-Didailler Catherine, Rousset-Rouvière Caroline, Ryckewaert Amélie, Schendel Adeline, Flammier Sacha, Acquaviva-Bourdain Cécile, Bacchetta Justine
机构信息
Reference Center for Rare Renal Diseases, ORKID and ERK-Net networks, Lyon University Hospital, Lyon, France.
Nephrology and Transplantation Department, Centre de référence MAladies Rénales Héréditaires de l'Enfant et de l'Adulte, Hôpital Necker-Enfants malades, AP-HP, Université de Paris, Paris, France.
出版信息
Kidney Int Rep. 2024 Dec 30;10(4):1020-1036. doi: 10.1016/j.ekir.2024.12.033. eCollection 2025 Apr.
INTRODUCTION
Lumasiran is a drug used in RNA-interference (RNAi) therapy for primary hyperoxaluria type 1 (PH1). Data on its efficacy and safety mainly come from industry-sponsored trials.
METHODS
For postmarketing follow-up, French authorities requested a quasi-exhaustive retrospective and prospective study over 5 years for patients receiving lumasiran, requiring the inclusion of at least 90% of patients, named as the DAILY-LUMA cohort (NCT06225882). Here, we analyzed data from all patients who were not previously included in the industry-sponsored trials and had received lumasiran for at least 2 years.
RESULTS
We included 38 patients, 22 from DAILY-A (i.e., estimated glomerular filtration rate (eGFR) > 45 ml/min per 1.73 m, age ≥ 6 years), 6 from DAILY-B (i.e., eGFR > 45 ml/min per 1.73 m, age < 6 years), and 10 from DAILY-C (i.e., all ages, eGFR < 45 ml/min per 1.73 m, 6 on dialysis). In DAILY-A and DAILY-B, decreased urinary oxalate-to-creatinine (UOx/creat) ratio, stable eGFR, and decrease in both nephrocalcinosis severity and stone numbers were observed, with a progressive tapering of conservative therapies. The decreased proportion of patients with nocturnal hydration and G-tubes overtime likely reflects improved quality of life. With a low number of patients - 2 patients on peritoneal dialysis and 3 patients with infantile oxalosis - the results are less conclusive for DAILY-C; however, in older patients, change in plasma oxalate (POx) levels is similar to previously published data. Tolerance was good with no severe side effects; injection site reactions, abdominal pain, and headaches were the main adverse events.
CONCLUSION
DAILY-LUMA is the largest cohort of patients receiving lumasiran in real life, confirming its safety and efficacy at 2 years.
引言
鲁马西拉是一种用于1型原发性高草酸尿症（PH1）的RNA干扰（RNAi）疗法药物。其疗效和安全性数据主要来自行业赞助的试验。
方法
为进行上市后随访，法国当局要求对接受鲁马西拉治疗的患者进行一项为期5年的近乎详尽的回顾性和前瞻性研究，要求纳入至少90%的患者，命名为DAILY-LUMA队列（NCT06225882）。在此，我们分析了所有未纳入行业赞助试验且接受鲁马西拉治疗至少2年的患者的数据。
结果
我们纳入了38例患者，其中22例来自DAILY-A（即估计肾小球滤过率（eGFR）>45 ml/min/1.73 m²，年龄≥6岁），6例来自DAILY-B（即eGFR>45 ml/min/1.73 m²，年龄<6岁），10例来自DAILY-C（即所有年龄段，eGFR<45 ml/min/1.73 m²，6例接受透析）。在DAILY-A和DAILY-B中，观察到尿草酸与肌酐（UOx/creat）比值降低、eGFR稳定、肾钙质沉着症严重程度和结石数量减少，同时保守治疗逐渐减少。夜间补液和胃造瘘管使用患者比例随时间下降可能反映了生活质量的改善。由于患者数量较少——2例接受腹膜透析，3例患有婴儿型草酸中毒——DAILY-C的结果不太具有决定性；然而，在老年患者中，血浆草酸（POx）水平的变化与先前发表的数据相似。耐受性良好，无严重副作用；注射部位反应、腹痛和头痛是主要不良事件。
结论
DAILY-LUMA是现实生活中接受鲁马西拉治疗的最大患者队列，证实了其在2年时的安全性和有效性。
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