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对临床上可用于治疗肢端肥大症的生长抑素类似物制剂的批判性分析。

A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly.

作者信息

Murray Robert D, Melmed Shlomo

机构信息

Department of Endocrinology, Leeds Teaching Hospitals National Health Service Trust, Leeds, UK.

出版信息

J Clin Endocrinol Metab. 2008 Aug;93(8):2957-68. doi: 10.1210/jc.2008-0027. Epub 2008 May 13.

Abstract

CONTEXT

Short and long-acting somatostatin (SRIF) analogs are approved for clinical use in acromegaly. Recent analysis of the relative efficacy of octreotide LAR and lanreotide SR on the GH-IGF-I axis in acromegaly favored octreotide LAR in the secondary treatment of patients not preselected by SRIF responsiveness. A novel aqueous formulation of lanreotide, lanreotide Autogel (ATG), has recently been approved and is the predominant (and only in the United States) formulation of lanreotide used clinically.

OBJECTIVE

We performed a critical review of SRIF analog treatment to establish the relative efficacy of three clinically available SRIF analog preparations, octreotide LAR, lanreotide SR, and lanreotide ATG (Somatuline depot in the United States) in control of the GH-IGF-I axis in acromegaly.

DATA SOURCES

Data were drawn from MEDLINE and the bibliography of analyses of long-acting SRIF analogs.

DATA COLLECTION

We reviewed the largest studies of sc octreotide, octreotide LAR, and lanreotide SR, all that included biochemical end-point data for lanreotide ATG, and studies that directly compared the efficacy of octreotide LAR and lanreotide SR.

DATA SYNTHESIS

Caveats considered included differences in baseline GH and IGF-I values, patient selection, and interassay and intraassay variability, confounding the analysis. Studies comparing patients treated contiguously with lanreotide SR and octreotide LAR are fraught with methodological problems, however, are suggestive of marginally greater efficacy in control of the GH-IGF-I axis for octreotide LAR. Lanreotide ATG shows noninferiority to lanreotide SR. Five small studies directly comparing octreotide LAR and lanreotide ATG suggest no significant differences between these preparations in control of biochemical end-points.

CONCLUSION

Lanreotide ATG and octreotide LAR are equivalent in the control of symptoms and biochemical markers in patients with acromegaly.

摘要

背景

短效和长效生长抑素(SRIF)类似物已被批准用于肢端肥大症的临床治疗。最近对奥曲肽长效释放剂(LAR)和兰瑞肽SR在肢端肥大症患者生长激素(GH)-胰岛素样生长因子-Ⅰ(IGF-Ⅰ)轴上的相对疗效分析表明,在未根据SRIF反应性预先选择的患者的二线治疗中,奥曲肽LAR更具优势。一种新型的兰瑞肽水性制剂——兰瑞肽长效凝胶(ATG)最近已获批准,并且是临床上使用的兰瑞肽的主要(在美国是唯一)制剂。

目的

我们对SRIF类似物治疗进行了批判性综述,以确定三种临床可用的SRIF类似物制剂——奥曲肽LAR、兰瑞肽SR和兰瑞肽ATG(在美国为索马杜林长效注射剂)在控制肢端肥大症患者GH-IGF-Ⅰ轴方面的相对疗效。

数据来源

数据取自MEDLINE以及长效SRIF类似物分析的参考文献。

数据收集

我们回顾了皮下注射奥曲肽、奥曲肽LAR和兰瑞肽SR的最大规模研究,所有纳入了兰瑞肽ATG生化终点数据的研究,以及直接比较奥曲肽LAR和兰瑞肽SR疗效的研究。

数据综合

考虑到的注意事项包括基线GH和IGF-Ⅰ值的差异、患者选择以及测定间和测定内的变异性,这些因素混淆了分析。比较连续接受兰瑞肽SR和奥曲肽LAR治疗患者的研究存在方法学问题,然而,提示奥曲肽LAR在控制GH-IGF-Ⅰ轴方面疗效略优。兰瑞肽ATG显示出与兰瑞肽SR非劣效。五项直接比较奥曲肽LAR和兰瑞肽ATG的小型研究表明,这些制剂在控制生化终点方面无显著差异。

结论

兰瑞肽ATG和奥曲肽LAR在控制肢端肥大症患者症状和生化指标方面等效。

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