Safety and efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH deficiency (GHD)
Safety and efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH deficiency (GHD)
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DOI：
10.1016/j.ghir.2007.12.001
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发表时间：
2008-08-01
影响因子：
1.4
通讯作者：
Shimatsu, A.
中科院分区：
文献类型：
--
作者：
Chihara, K.;Kato, Y.;Shimatsu, A.
目的：评估使用基于血清胰岛素样生长因子 (IGF-I) 浓度的 GH 剂量方案对患有 GH 缺乏 (GHD) 的日本成人进行生长激素 (GH) 替代疗法的效果。 设计：在这项多中心、非对照、开放标签研究中，患有 GHD 的日本成人在之前的随机分组中接受过 GH 替代疗法（GH-GH 组，n = 35）或安慰剂（安慰剂-GH 组，n = 36），双盲、安慰剂对照试验采用 GH 替代疗法治疗 48 周。 GH治疗开始前8周，皮下注射剂量为0.003 mg/kg/天，此后调整剂量，将患者血清IGF-I水平维持在根据年龄和性别调整的参考范围内。在整个研究过程中测量了身体成分、血清脂质、血清 IGF-I 和 IGF 结合蛋白-3 (IGFBP-3) 水平。还确定了症状和生活质量评分。 结果：第 24 周和第 48 周时，去脂体重 (LBM) 与基线（之前的双盲试验结束时）相比有所增加，GH-GH 组在第 48 周时平均 (+/- SD) 增加了 1.3% (+/- 4.2%)（与之前的双盲试验开始相比增加了 6.6% [+/- 6.0%]），并且安慰剂-GH 组增加了 4.7% (+/- 5.9%)。 GH-GH 组的体脂量 (BFM) 较基线略有增加，第 48 周平均增加 2.9 +/- 10.6%（与之前双盲试验开始时 48 周相比减少了 7.8% [+/- 15.0%]），但安慰剂-GH 组在第 48 周下降了 6.5% (+/- 11.7%)。 GH-GH 组的血清脂质与基线相比没有变化或略有增加，但安慰剂-GH 组患者的血脂状况有所改善。 在双盲研究期间接受安慰剂的患者中，这项开放标签研究中的个体化 GH 治疗使 CO GHD 患者在 48 周时的平均 LBM 增加了 6.2 +/- 6.8%，而 AO GHD 患者则增加了 3.0 +/- 4.4%。第48周时，女性的平均LBM和平均BFM的变化分别为+4.1 +/- 4.5%和-2.4 +/- 10.5%，而男性的平均LBM和平均BFM的变化分别为+5.0 +/- 6.7%和-8.9 +/- 11.8%。在双盲研究期间接受 GH 治疗的患者中，24 周和 48 周后 LBM、BFM 和 IGF-I SD 评分的总体变化较小，亚组之间没有显着差异。 虽然 GH-GH 组和安慰剂-GH 组的总体不良事件发生率大致相似（分别为 97% 和 89%），但 GH-GH 组的治疗相关事件发生率较高（83% vs 42%）。安慰剂-GH 组）。两个治疗组中的大多数不良事件都是轻度或中度严重性，并且没有临床意义。 IGF-I水平调整治疗方案期间水肿和高IGF-I病例的发生率低于之前的固定剂量滴定期间的发生率。结论：日本成人GHD患者长期GH替代治疗的耐受性良好。 GH 治疗维持了双盲研究中先前接受治疗的患者（GH-GH 组）身体成分和血脂状况的改善，并改善了先前未接受治疗的患者（安慰剂-GH 组）的这些参数。基于 IGF-I 水平的个体化 GH 给药耐受性良好且有效。 (c) 2007 Elsevier Ltd. 保留所有权利。
Objectives: To assess the effects of a growth hormone (GH) replacement therapy using a GH dose regimen based on serum insulin-like growth factor (IGF-I) concentrations in Japanese adults with GH deficiency (GHD).Design: In this multicentre, uncontrolled, open-label study, Japanese adults with GHD who had received either GH replacement therapy (GH-GH group, n = 35) or placebo (Placebo-GH group, n = 36) in a previous randomised, double-blind, placebo-controlled trial were treated with GH replacement therapy for 48 weeks. GH treatment was started at a dose of 0.003 mg/kg/day administered by subcutaneous injection for the first 8 weeks, after which the dose was adjusted to maintain patients' serum IGF-I levels within the reference range adjusted for age and gender. Body composition, serum lipids, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels were measured throughout study. Symptom and quality of life scores were also determined.Results: Lean body mass (LBM) was increased compared with baseline (the end of the preceding double-blind trial) at 24 and 48 weeks, with a mean (+/- SD) increase of 1.3% (+/- 4.2%) at week 48 in the GH-GH group (an increase of 6.6% [+/- 6.0%] from the start of the preceding double-blind trial) and a larger increase of 4.7% (+/- 5.9%) in the Placebo-GH group. Body fat mass (BFM) increased slightly from baseline in the GH-GH group with a mean increase of 2.9 +/- 10.6% at week 48 (a decrease from the start of the preceding double-blind trial at 48 weeks of 7.8% [+/- 15.0%]) but decreased by 6.5% (+/- 11.7%) at week 48 in the Placebo-GH group. Serum lipids were unchanged or slightly increased from baseline in the GH-GH group but patients' lipid profiles improved in the Placebo-GH group.In patients who received placebo during the double-blind study, individualised GH therapy in this open-label study increased mean LBM at 48 weeks by 6.2 +/- 6.8% in patients with CO GHD and by 3.0 +/- 4.4% in patients with AO GHD. Changes in mean LBM and mean BFM at week 48 were +4.1 +/- 4.5% and -2.4 +/- 10.5%, respectively, in females and +5.0 +/- 6.7% and -8.9 +/- 11.8%, respectively, in males. In patients who received GH treatment during the double-blind study, overall changes in LBM, BFM and IGF-I SD score after 24 weeks and 48 weeks were small, with no significant differences between subgroups.While the overall incidence of adverse events was broadly similar in the GH-GH and Placebo-GH groups (97% and 89%, respectively), the incidence of treatment-related events was higher in the GH-GH group (83% vs 42% in the Placebo-GH group). Most adverse events in both treatment groups were of mild or moderate severity and not clinically significant. The incidences of oedema and cases of high IGF-I during the IGF-I level-adjusted treatment regimen were lower than those during the preceding fixed dose titration.Conclusion: Long-term GH replacement therapy was well tolerated in Japanese adults with GHD. GH treatment maintained the improvements in body composition and lipid profiles in the patients previously treated in the double-blind study (GH-GH group) and improved these parameters in previously untreated patients (Placebo-GH group). Individualised GH administration based on IGF-I levels was well-tolerated and effective. (c) 2007 Elsevier Ltd. All rights reserved.