伴全身型多发性内分泌腺瘤病的常染色体显性遗传多囊肾病或常染色体显性遗传多囊肝病伴严重肝累及患者使用长效生长抑素类似物帕瑞肽治疗：一项随机临床试验。
Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement: A Randomized Clinical Trial.
机构信息
Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota.
Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
出版信息
Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1267-1278. doi: 10.2215/CJN.13661119. Epub 2020 Aug 25.
BACKGROUND AND OBJECTIVES
We assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Individuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life.
RESULTS
Of 48 subjects randomized, 41 completed total liver volume measurements (=29 pasireotide long-acting release and =12 placebo). From baseline, there were -99±189 ml/m absolute and -3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (<0.001 for both). Total kidney volumes decreased by -12±34 ml/m and -1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (=0.05 for both). Changes in eGFR were similar between groups. Among the =48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; <0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (=0.001).
CONCLUSIONS
Another somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes).
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Pasireotide LAR in Severe Polycystic Liver Disease, NCT01670110 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3.
背景和目的
我们评估了另一种生长抑素受体类似物——帕瑞肽长效释放剂型，在严重多囊肝疾病和常染色体显性多囊肾病患者中的安全性和疗效。帕瑞肽长效释放剂型具有更广泛的结合谱和更高的亲和力，可能具有更好的疗效。
设计、地点、参与者和测量：严重多囊肝疾病患者按照 2:1 的比例，在一项为期 1 年的、双盲、随机试验中被分配接受帕瑞肽长效释放剂型或安慰剂治疗。主要结局是总肝体积的变化；次要结局是总肾体积、eGFR 和生活质量的变化。
结果
在 48 名随机分配的患者中，41 名完成了总肝体积测量（=29 名帕瑞肽长效释放剂型和=12 名安慰剂）。从基线开始，帕瑞肽长效释放剂型组的总肝体积高度调整后的年度变化绝对值为-99±189ml/m，变化率为-3%±7%（从 2582±1381ml/m 降至 2479±1317ml/m），而安慰剂组的绝对值为 136±117ml/m，变化率为 6%±7%（从 2387±759ml/m 增至 2533±770ml/m）（均<0.001）。与安慰剂组相比，帕瑞肽长效释放剂型组的总肾体积减少了-12±34ml/m，变化率为-1%±4%，而安慰剂组的总肾体积增加了 21±21ml/m，变化率为 4%±5%（均=0.05）。两组的 eGFR 变化相似。在 48 名随机分配的患者中，不良事件包括高血糖（帕瑞肽长效释放剂型组 33 例中的 26 例[79%]，安慰剂组 15 例中的 4 例[27%]；<0.001），在 47 名基线无糖尿病的患者中，帕瑞肽长效释放剂型组的 32 例中有 19 例（59%），安慰剂组的 15 例中有 1 例（7%）发生糖尿病（=0.001）。
结论
另一种生长抑素类似物——帕瑞肽长效释放剂型可减缓总肝体积/总肾体积增长率的进行性增加，而不影响 GFR 下降。患者经历了更高频率的不良事件（高血糖和糖尿病）。
临床试验注册名称和注册号
帕瑞肽长效释放剂型在严重多囊肝疾病中的应用，NCT01670110 播客：本文包含一个播客，网址为 https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3。
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