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Abstract：
UNASSIGNED: Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalizable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD.
UNASSIGNED: Agalsidase beta-treated adult patients (aged ≥16 years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5 years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+ years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalization in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16 years.
UNASSIGNED: Overall, eGFR slopes for 1:1-matched untreated and treated adult patients [122 pairs (72.1% male)] were -3.19 and -1.47 mL/min/1.73 m2/year, respectively (reduction in rate of decline = 53.9%, P = .007), and for X:X-matched [122 untreated/950 treated (59.4% male)] were -3.29 and -1.56 mL/min/1.73 m2/year, respectively (reduction in rate of decline = 52.6%, P < .001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 (P = .003) and 0.67 (P = .008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalized in most within 6 months of treatment initiation.
UNASSIGNED: Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalization of elevated pre-treatment levels in most patients.
UNASSIGNED: Agalsidase beta-treated adult patients (aged ≥16 years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5 years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+ years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalization in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16 years.
UNASSIGNED: Overall, eGFR slopes for 1:1-matched untreated and treated adult patients [122 pairs (72.1% male)] were -3.19 and -1.47 mL/min/1.73 m2/year, respectively (reduction in rate of decline = 53.9%, P = .007), and for X:X-matched [122 untreated/950 treated (59.4% male)] were -3.29 and -1.56 mL/min/1.73 m2/year, respectively (reduction in rate of decline = 52.6%, P < .001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 (P = .003) and 0.67 (P = .008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalized in most within 6 months of treatment initiation.
UNASSIGNED: Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalization of elevated pre-treatment levels in most patients.
摘要：
■法布里病患者（FD，α-半乳糖苷酶A缺乏或缺乏)积累鞘糖脂，导致肾脏进行性功能障碍，心脏和神经系统。在外部试验开始后，可推广的真实世界结果是有限的。我们在一项对治疗和未治疗的FD患者的匹配分析中，研究了长期的半乳糖苷酶β治疗与估计的肾小球滤过率（eGFR）随时间变化的相关性以及发生复合临床事件的风险。
■法布里登记处的阿胶糖苷酶β治疗的成年患者（年龄≥16岁）和自然史队列中未经治疗的成年患者进行1：1和X：X匹配（每位未经治疗的患者发生一次和多次发生，分别)按性别，表型,年龄和(用于eGFR斜率分析)基线eGFR。结果包括5年eGFR斜率和复合临床事件风险(心血管，脑血管或肾脏事件，或死亡)超过10年。作为儿科患者治疗反应的替代指标，在2岁至<16岁的患者中,评估了从治疗开始开始时血浆中的globotriaosceramide(GL-3)经历正常化的百分比.
■总的来说，1：1匹配的未经治疗和治疗的成年患者的eGFR斜率[122对（72.1％男性）]为-3.19和-1.47mL/min/1.73m2/年，分别(下降率=53.9%，P=.007)，对于X：X匹配[122未处理/950处理（59.4％男性）]为-3.29和-1.56mL/min/1.73m2/年，(降幅分别为52.6%，P<.001)。半乳糖苷酶β治疗与较低的临床事件风险相关，1：1匹配和X：X匹配分析的风险比为0.41（P=0.003）和0.67（P=0.008），分别。儿科患者的血浆GL-3显着下降，大多数在治疗开始后6个月内恢复正常。
■阿胶糖苷酶β治疗可保护成年FD患者的肾功能并延迟严重临床事件的进展。在儿科患者中分析的血浆GL-3水平显示大多数患者中升高的治疗前水平正常化。
■法布里登记处的阿胶糖苷酶β治疗的成年患者（年龄≥16岁）和自然史队列中未经治疗的成年患者进行1：1和X：X匹配（每位未经治疗的患者发生一次和多次发生，分别)按性别，表型,年龄和(用于eGFR斜率分析)基线eGFR。结果包括5年eGFR斜率和复合临床事件风险(心血管，脑血管或肾脏事件，或死亡)超过10年。作为儿科患者治疗反应的替代指标，在2岁至<16岁的患者中,评估了从治疗开始开始时血浆中的globotriaosceramide(GL-3)经历正常化的百分比.
■总的来说，1：1匹配的未经治疗和治疗的成年患者的eGFR斜率[122对（72.1％男性）]为-3.19和-1.47mL/min/1.73m2/年，分别(下降率=53.9%，P=.007)，对于X：X匹配[122未处理/950处理（59.4％男性）]为-3.29和-1.56mL/min/1.73m2/年，(降幅分别为52.6%，P<.001)。半乳糖苷酶β治疗与较低的临床事件风险相关，1：1匹配和X：X匹配分析的风险比为0.41（P=0.003）和0.67（P=0.008），分别。儿科患者的血浆GL-3显着下降，大多数在治疗开始后6个月内恢复正常。
■阿胶糖苷酶β治疗可保护成年FD患者的肾功能并延迟严重临床事件的进展。在儿科患者中分析的血浆GL-3水平显示大多数患者中升高的治疗前水平正常化。
