Long-term safety and efficacy of enzyme replacement therapy for Fabry disease
Long-term safety and efficacy of enzyme replacement therapy for Fabry disease
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DOI：
10.1086/422366
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发表时间：
2004-07-01
影响因子：
9.8
通讯作者：
Germain, DP
中科院分区：
文献类型：
--
作者：
Wilcox, WR;Banikazemi, M;Germain, DP
在其他地方，我们报告了重组人α-半乳糖苷酶A（rh-alphaGalA）替代治疗法布里病患者的多中心III期试验的安全性和有效性结果。所有58名入组20周III期双盲、随机化和安慰剂对照研究的患者随后在一项正在进行的开放标签扩展研究中每两周接受1 mg/kg rh-alphaGalA（半乳糖苷酶β，Fabrazyme，Genzyme Corporation）。长期疗效的证据，即使在产生抗rh-alphaGalA IgG抗体的患者中，包括扩展研究30个月期间持续正常的平均血浆神经酰胺（GL-3）水平和治疗30个月后接受皮肤活检的98%（39/40）患者的持续毛细血管内皮GL-3清除率（原始安慰剂组）或36个月（原始酶处理组）。治疗30-36个月后，平均血清肌酐水平和估计的肾小球滤过率也保持稳定。输注相关反应随着时间的推移而降低，抗rh-alphaGalA IgG抗体滴度也是如此。在血清转化的患者中，治疗30-36个月后，7名患者耐受（未检测到IgG抗体），59%的患者抗体滴度下降大于或等于4倍。在扩展试验开始30个月时，3例患者因血清IgE或皮肤试验阳性而退出研究;然而，在本报告时，所有患者均已成功再激发。因此，使用半乳糖苷酶β进行30-36个月的酶替代治疗导致血浆GL-3水平持续降低、内皮GL-3清除持续、肾功能稳定和有利的安全性特征。
Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha-galactosidase A (rh-alphaGalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alphaGalA ( agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh-alphaGalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh-alphaGalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had greater than or equal to4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile.