Departments of Human Genetics and Medicine (Hematology), University of Miami Miller School of Medicine, Miami, FL, USA.
Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo, Bandeirantes Av., 3900 - 5th floor - Off D506 - HC Criança, São Paulo, Brazil.
Mol Genet Metab. 2021 Feb;132(2):100-111. doi: 10.1016/j.ymgme.2020.12.295. Epub 2021 Jan 8.
Alglucerase enzyme replacement therapy was approved for Gaucher disease (GD) in the United States in 1991; imiglucerase in 1994. We report hematologic, visceral, bone pain, bone crisis, height, weight, and Body Mass Index (BMI) outcomes in patients treated for 20 (±3) years with subset analyses based on pre-treatment severity, genotype, and age at treatment initiation.
GD type 1 (GD1) patients in the ICGG Gaucher Registry with complete sets of baseline, 10-year, and 20-year data are included (N = 475). Ten-year and 20-year data are compared to pre-treatment baseline, stratified by splenectomy status.
Non-splenectomized patients: Improvements observed at 10 years were maintained at 20 years for most outcomes. Mean changes from baseline at 10 and 20 years, respectively, were: spleen volume: 18.2 multiples of normal (MN) to 5.1 MN and 4.2 MN; liver volume: 1.8 MN to 1.0 MN and 1.0 MN; hemoglobin: 11.4 g/dL to 13.7 g/dL and 13.8 g/dL; platelet count: 91.6 × 10/L to 168.0 × 10/L and 169.1 × 10/L; without bone crisis: 85.0% to 98.2% and 96.5%; without bone pain: 52.5% to 72.0% at 10 years, no significant change at 20 years (58.5%). Splenectomized patients: significant changes were observed in liver volume: 2.3 MN to 1.1 MN and 1.0 MN; hemoglobin: 11.7 g/dL to 13.3 g/dL and 13.4 g/dL; platelet count: 229.1 × 10/L to 288.1 × 10/L and 257.0 × 10/L; without bone crisis: 52.2% to 91.3% and 100%; without bone pain: 16.3% to 30.6% (not significant) and 46.9%. Similar results were found in each of the subset analyses. Patients who start treatment during childhood have normal weight and height in young adulthood. Many treated adult patients are overweight or obese; however, this is consistent with BMI trends observed in the general population. After 1-2 years, the average biweekly imiglucerase dose is ~40 units/kg body weight.
Imiglucerase is an effective, long-term treatment for GD1. In a long-term observational setting, improvements seen during early treatment years are sustained by continuing treatment for 20 years, except for bone pain in non-splenectomized patients. These results are consistent when analyzed by different patient subsets, including by disease severity.
阿糖苷酶替代疗法于 1991 年在美国获得 Gaucher 病（GD）的批准；伊米苷酶于 1994 年获得批准。我们报告了经过 20（±3）年治疗的患者的血液学、内脏、骨痛、骨危象、身高、体重和体重指数（BMI）结果，并根据治疗前的严重程度、基因型和起始治疗时的年龄进行了亚组分析。
ICGG Gaucher 登记处中具有完整基线、10 年和 20 年数据的 GD1 型（GD1）患者包括在内（N=475）。根据脾切除术的情况，将 10 年和 20 年的数据与基线进行比较。
未行脾切除术的患者：大多数结局在 10 年后观察到的改善在 20 年后仍保持不变。从基线到 10 年和 20 年的平均变化分别为：脾脏体积：18.2 个正常倍数（MN）至 5.1 MN 和 4.2 MN；肝脏体积：1.8 MN 至 1.0 MN 和 1.0 MN；血红蛋白：11.4 g/dL 至 13.7 g/dL 和 13.8 g/dL；血小板计数：91.6×10/L 至 168.0×10/L 和 169.1×10/L；无骨危象：85.0%至 98.2%和 96.5%；无骨痛：52.5%至 72.0%，10 年后无明显变化（58.5%）。行脾切除术的患者：肝脏体积有显著变化：2.3 MN 至 1.1 MN 和 1.0 MN；血红蛋白：11.7 g/dL 至 13.3 g/dL 和 13.4 g/dL；血小板计数：229.1×10/L 至 288.1×10/L 和 257.0×10/L；无骨危象：52.2%至 91.3%和 100%；无骨痛：16.3%至 30.6%（无显著性）和 46.9%。在每个亚组分析中都发现了类似的结果。在儿童期开始治疗的患者在成年早期体重和身高正常。许多接受治疗的成年患者超重或肥胖；然而，这与一般人群中观察到的 BMI 趋势一致。治疗 1-2 年后，伊米苷酶的平均两周剂量约为 40 单位/公斤体重。
伊米苷酶是一种有效的 GD1 长期治疗方法。在长期观察性研究中，除了未行脾切除术的患者的骨痛外，早期治疗期间观察到的改善在继续治疗 20 年后仍持续存在。对于不同的患者亚组，包括疾病严重程度的患者亚组，分析结果一致。
