Neuroendocrinology Research Center, Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
J Clin Endocrinol Metab. 2023 Nov 17;108(12):e1571-e1579. doi: 10.1210/clinem/dgad378.
Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control.
As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed.
A retrospective analysis was performed using a prospectively maintained database of all patients with acromegaly from our primary care center who were enrolled in clinical studies with pasireotide (first visit November 2008). The main outcome measures were safety and biochemical control (age-adjusted IGF-I ≤ upper limit of normal).
Patients (n = 50) entered 4 parental studies and 30 continued in the rollover; at data cutoff (June 2022), 27 were still receiving pasireotide. Overall, median (range) exposure was 58 (3-137) months. Normal IGF-I was achieved in 54%, and acromegaly symptoms and quality of life were improved with treatment. No predictors of pasireotide response were identified; however, controlled patients had smaller tumors and lower GH at baseline. Tumor volume reduction occurred in 63% of evaluable patients (n = 10/16). Most patients presented hyperglycemic events, including 63.2% of patients with normal glucose before treatment. Older patients and those with higher IGF-I, glucose, and HbA1c at baseline had higher glucose and HbA1c during pasireotide treatment.
Pasireotide provided clinical benefit and was well tolerated for more than 11 years of treatment in acromegaly patients, most of whom were resistant to first-generation SRLs.
肢端肥大症是一种罕见的、慢性的、使人衰弱的疾病，由生长激素（GH）的长期过度分泌和胰岛素样生长因子 I（IGF-I）的过度产生引起。包括生长抑素受体配体（SRL）帕瑞肽在内的医学治疗方法经常被用于恢复生化控制。
由于患者通常接受长期治疗，因此需要来自真实环境的长期数据。
对来自我们基层医疗中心的所有接受帕瑞肽治疗的肢端肥大症患者进行回顾性分析，这些患者参加了我们的临床研究（第一次就诊时间为 2008 年 11 月）。主要观察指标是安全性和生化控制（年龄调整后的 IGF-I≤正常上限）。
患者（n=50）参加了 4 项原始研究，30 项继续进行滚动研究；截至数据截止日期（2022 年 6 月），27 名患者仍在接受帕瑞肽治疗。总体而言，中位（范围）暴露时间为 58（3-137）个月。54%的患者达到了正常的 IGF-I，治疗后肢端肥大症症状和生活质量得到改善。未确定帕瑞肽反应的预测因素；然而，控制良好的患者基线时肿瘤较小且 GH 较低。可评估的 16 名患者中有 63%（n=10）的肿瘤体积缩小。大多数患者出现高血糖事件，包括治疗前血糖正常的患者中有 63.2%。基线时 IGF-I、血糖和 HbA1c 较高的老年患者和患者在帕瑞肽治疗期间血糖和 HbA1c 较高。
帕瑞肽治疗肢端肥大症超过 11 年，临床获益且耐受性良好，大多数患者对第一代 SRL 耐药。
