Purpose: To determine the impact of initiating enzyme replacement therapy (ERT) with agalsidase alfa early in the course of Fabry disease, we evaluated renal and cardiac outcomes for ≤ 10 years after ERT initiation in males from the Fabry Outcome Survey (FOS).
Patients and Methods: Male patients from FOS were stratified into three cohorts by age at ERT initiation: ≤ 18 years (cohort 1), > 18 and ≤ 30 years (cohort 2), and > 30 years (cohort 3). Analysis included age at symptom onset, diagnosis, and ERT initiation; ERT duration; FOS-Mainz Severity Score Index (FOS-MSSI); estimated glomerular filtration rate (eGFR); proteinuria level; and left ventricular mass indexed to height (LVMI). Mixed-effect models estimated renal and cardiac outcomes during follow-up between and within cohorts.
Findings: The analysis included 560 male patients: 151 (27.0%) in cohort 1, 155 (27.7%) in cohort 2, and 254 (45.4%) in cohort 3. Mean±SD duration of ERT for cohorts 1, 2, and 3 was 6.3± 4.3, 8.6± 4.9, and 7.9± 4.9 years, respectively. Mean±SD baseline FOS-MSSI scores increased with age from 9.8± 7.2 in cohort 1 to 24.7± 11.4 in cohort 3. Cohort 3 showed the lowest baseline mean±SD value for eGFR (87.1± 29.0 mL/min/1.73m²) and highest baseline mean±SD values for proteinuria (801.9± 952.6 mg/day) and LVMI (56.7± 16.0 g/m^2.7) among the three cohorts. Evaluation of mean annual rates of change in eGFR, proteinuria, and LVMI revealed no significant differences in any parameter for cohort 1. For cohort 2, proteinuria and LVMI remained stable, whereas eGFR significantly deteriorated annually (– 1.12 mL/min/1.73m²; P< 0.001). Cohort 3 demonstrated significant annual deteriorations in eGFR (– 2.60 mL/min/1.73m²; P< 0.001), proteinuria (+34.10 mg/day; P< 0.001), and LVMI (+0.59 g/m^2.7; P=0.001).
Implications: Renal and/or cardiac disease progression appears attenuated in patients starting ERT in childhood or early adulthood versus patients starting ERT in later adulthood. These findings support early ERT initiation in Fabry disease. ClinicalTrials.gov identifier: NCT03289065.

Keywords: agalsidase alfa, Fabry disease, enzyme replacement therapy, Fabry Outcome Survey, estimated glomerular filtration rate, left ventricular hypertrophy


中文翻译：

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法布里结果调查中男性参与者在 18 岁前后开始阿加糖酶阿尔法酶替代治疗的肾脏和心脏结果分析。


目的：为了确定在法布里病病程早期开始使用阿加糖酶α进行酶替代疗法 (ERT) 的影响，我们根据法布里结果调查 (FOS) 评估了男性开始 ERT 后 ≤ 10 年内的肾脏和心脏结局。

患者和方法： FOS 的男性患者按开始 ERT 时的年龄分为三个队列：≤ 18 岁（队列 1）、> 18 岁且≤ 30 岁（队列 2）和 > 30 岁（队列 3）。分析包括症状出现时的年龄、诊断和开始 ERT； ERT 持续时间； FOS-美因茨严重程度评分指数 (FOS-MSSI)；估计肾小球滤过率（eGFR）；蛋白尿水平；和与身高指数相关的左心室质量 (LVMI)。混合效应模型评估了队列间和队列内随访期间的肾脏和心脏结果。

结果：分析包括 560 名男性患者：队列 1 中有 151 名 (27.0%)，队列 2 中有 155 名 (27.7%)，队列 3 中有 254 名 (45.4%)。队列 1、2 和 2 的 ERT 持续时间的平均值±SD 3 分别为 6.3±4.3、8.6±4.9 和 7.9±4.9 年。平均值±SD 基线 FOS-MSSI 评分随着年龄的增长从队列 1 中的 9.8± 7.2 增加到队列 3 中的 24.7± 11.4。队列 3 显示 eGFR 的最低基线平均值±SD 值 (87.1± 29.0 mL/min/1.73m ² )三个队列中蛋白尿的最高基线平均值±SD 值（801.9±952.6 mg/天）和LVMI（56.7±16.0 g/m ^2.7 ）。对 eGFR、蛋白尿和 LVMI 的平均年变化率的评估显示，队列 1 的任何参数均无显着差异。对于队列 2，蛋白尿和 LVMI 保持稳定，而 eGFR 每年显着恶化 (– 1.12 mL/min/1.73m ² ; P <0.001）。第 3 组的 eGFR（– 2.60 mL/min/1.73m ² ； P < 0.001）、蛋白尿（+34.10 mg/天； P < 0.001）和 LVMI（+0.59 g/m ^2.7 ； P =0.001）每年显着恶化）。

意义：与成年后期开始 ERT 的患者相比，在儿童期或成年早期开始 ERT 的患者的肾脏和/或心脏病进展似乎有所减弱。这些发现支持法布里病的早期 ERT 启动。 ClinicalTrials.gov 标识符：NCT03289065。


关键词：阿加糖酶α、法布里病、酶替代疗法、法布里结果调查、估计肾小球滤过率、左心室肥厚