Abstract

Background

Fabry disease is a rare, X-linked genetic disorder that, if untreated in patients with the Classic phenotype, often progresses to end-stage kidney disease. This meta-analysis determined the effect of agalsidase beta on loss of estimated glomerular filtration rate (eGFR) in the Classic phenotype using an expansive evidence base of individual patient-level data.

Methods

The evidence base included four Sanofi-Genzyme studies and six studies from a systematic literature review. These were restricted to Classic Fabry patients meeting the eligibility criteria from Phases III and IV agalsidase beta trials, including 315 patients (161 treated). Linear regression was first used to model annual change in eGFR for each patient and the resulting annualized eGFR slopes were modelled with treatment and covariates using quantile regression. These results were then used to estimate median annualized eGFR change in agalsidase beta treated versus untreated groups.

Results

Imbalances across treatment groups were found in baseline age, sex and proteinuria, but not in the use of renin–angiotensin system blockers. The adjusted model suggests that treated (agalsidase beta) patients experienced a slower median eGFR decrease [2.46 mL/min/1.73 m²/year slower; 95% confidence interval (CI) 0.63–4.29; P = 0.0087] than comparable untreated patients. The median eGFR decrease was 2.64 mL/min/1.73 m²/year slower (95% CI 0.53–4.78; P = 0.0141) in treated Classic males.

Conclusions

Using an expansive evidence base and robust modelling approach, these data indicate that agalsidase beta-treated patients with the Classic phenotype conserve their renal function better than untreated patients.

中文翻译：

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阿加糖酶β治疗减缓了经典法布里病患者估计的肾小球滤过率损失：来自个体患者数据荟萃分析的结果

摘要

背景

法布里病是一种罕见的 X 连锁遗传疾病，如果在具有经典表型的患者中未经治疗，通常会发展为终末期肾病。该荟萃分析使用个体患者水平数据的广泛证据基础确定了经典表型中阿加糖酶β对估计肾小球滤过率 (eGFR) 损失的影响。

方法

证据基础包括四项赛诺菲健赞研究和来自系统文献综述的六项研究。这些仅限于符合 III 期和 IV 期阿加糖酶β试验资格标准的 Classic Fabry 患者，包括 315 名患者（161 名接受治疗）。首先使用线性回归对每位患者的 eGFR 年度变化进行建模，并使用分位数回归对治疗和协变量对所得的年度化 eGFR 斜率进行建模。然后将这些结果用于估计阿加糖酶 β 治疗组与未治疗组的中位年化 eGFR 变化。

结果

在基线年龄、性别和蛋白尿方面发现了治疗组之间的不平衡，但在肾素-血管紧张素系统阻滞剂的使用方面没有发现。调整后的模型表明，接受治疗的（阿加糖酶β）患者中位 eGFR 下降较慢 [2.46 mL/min/1.73 m ² /year 减慢；95% 置信区间 (CI) 0.63–4.29；P = 0.0087] 与可比较的未治疗患者相比。在接受治疗的经典男性中，eGFR 下降的中位数为 2.64 mL/min/1.73 m ² /年（95% CI 0.53–4.78；P = 0.0141）。

结论

使用广泛的证据基础和稳健的建模方法，这些数据表明具有经典表型的阿加糖酶 β 治疗的患者比未治疗的患者更好地保护其肾功能。