University College London, London, UK.
Lancet. 2009 Dec 12;374(9706):1986-96. doi: 10.1016/S0140-6736(09)61493-8.
We analysed 5-year treatment with agalsidase alfa enzyme replacement therapy in patients with Fabry's disease who were enrolled in the Fabry Outcome Survey observational database (FOS).
Baseline and 5-year data were available for up to 181 adults (126 men) in FOS. Serial data for cardiac mass and function, renal function, pain, and quality of life were assessed. Safety and sensitivity analyses were done in patients with baseline and at least one relevant follow-up measurement during the 5 years (n=555 and n=475, respectively).
In patients with baseline cardiac hypertrophy, treatment resulted in a sustained reduction in left ventricular mass (LVM) index after 5 years (from 71.4 [SD 22.5] g/m(2.7) to 64.1 [18.7] g/m(2.7), p=0.0111) and a significant increase in midwall fractional shortening (MFS) from 14.3% (2.3) to 16.0% (3.8) after 3 years (p=0.02). In patients without baseline hypertrophy, LVM index and MFS remained stable. Mean yearly fall in estimated glomerular filtration rate versus baseline after 5 years of enzyme replacement therapy was -3.17 mL/min per 1.73 m(2) for men and -0.89 mL/min per 1.73 m(2) for women. Average pain, measured by Brief Pain Inventory score, improved significantly, from 3.7 (2.3) at baseline to 2.5 (2.4) after 5 years (p=0.0023). Quality of life, measured by deviation scores from normal EuroQol values, improved significantly, from -0.24 (0.3) at baseline to -0.17 (0.3) after 5 years (p=0.0483). Findings were confirmed by sensitivity analysis. No unexpected safety concerns were identified.
By comparison with historical natural history data for patients with Fabry's disease who were not treated with enzyme replacement therapy, long-term treatment with agalsidase alfa leads to substantial and sustained clinical benefits.
Shire Human Genetic Therapies AB.
我们分析了参加 Fabry 结局调查观察性数据库（FOS）的法布雷病患者接受阿加糖酶α酶替代疗法 5 年的治疗情况。
FOS 中最多有 181 名成人（126 名男性）可提供基线和 5 年的数据。评估了心脏质量和功能、肾功能、疼痛和生活质量的连续数据。对基线时和 5 年内至少有一次相关随访测量的患者进行了安全性和敏感性分析（分别有 555 名和 475 名患者）。
在基线时存在心脏肥大的患者中，治疗 5 年后左心室质量指数持续下降（从 71.4[22.5]g/m2.7 降至 64.1[18.7]g/m2.7，p=0.0111），3 年后中层壁缩短分数（MFS）从 14.3%（2.3）显著增加至 16.0%（3.8）（p=0.02）。在基线时无肥大的患者中，LVM 指数和 MFS 保持稳定。5 年酶替代治疗后，男性估计肾小球滤过率每年相对于基线的下降值为-3.17mL/min/1.73m2，女性为-0.89mL/min/1.73m2。用Brief Pain Inventory 评分测量的平均疼痛显著改善，从基线时的 3.7（2.3）降至 5 年后的 2.5（2.4）（p=0.0023）。用偏离正常 EuroQol 值的偏差评分测量的生活质量显著改善，从基线时的-0.24（0.3）降至 5 年后的-0.17（0.3）（p=0.0483）。敏感性分析证实了这些发现。未发现新的安全性问题。
与未接受酶替代治疗的法布雷病患者的历史自然病程数据相比，阿加糖酶α的长期治疗可带来显著且持续的临床获益。
Shire Human Genetic Therapies AB。
