Brazilian multicenter study on pegvisomant treatment in acromegaly

ABSTRACT Objective Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

摘要：
研究目的：本研究通过一项巴西多中心真实世界研究，旨在探究肢端肥大症（acromegaly）患者对培维索孟（pegvisomant, PEGV）的治疗应答情况。
研究对象与方法：回顾性分析接受培维索孟治疗的肢端肥大症患者在确诊时、治疗前及治疗期间的临床特征。纳入所有在培维索孟治疗期间至少完成两次胰岛素样生长因子-I（insulin-like growth factor-I, IGF-I）检测的患者。以治疗期间任意一次IGF-I水平恢复正常作为疗效判定标准。同时回顾分析安全性数据，并通过对比应答控制良好与应答控制不佳患者的临床特征，明确治疗应答的预测因素。
结果：本研究共纳入来自巴西10个医疗中心的109例患者，其中女性61例；确诊时中位年龄为34岁；95.3%的患者为垂体大腺瘤（macroadenomas）。患者既往接受的治疗包括手术治疗（89%）、放射治疗（34%）、生长抑素受体配体（somatostatin receptor ligands）治疗（99%）以及卡麦角林（cabergoline）治疗（67%）。培维索孟治疗前，患者的生长激素（growth hormone, GH）、IGF-I水平及IGF-I占正常上限百分比的中位值分别为4.3 μg/L、613 ng/mL及209%。48.6%的患者合并糖尿病前期或糖尿病，71%的患者存在肿瘤残余。除4例外，其余所有患者的初始给药剂量均为10 mg/日，最大给药剂量为30 mg/日，中位药物暴露时长为30.5个月。11%的患者采用培维索孟单药治疗。74.1%的患者治疗后实现IGF-I水平正常化。在合并糖尿病前期或糖尿病的患者中，56.6%的患者血糖控制情况得到改善。治疗应答的预测因素包括药物暴露时长、治疗前GH及IGF-I水平。6.5%的患者出现肿瘤增大，9.2%的患者出现肝酶升高。6例患者停用培维索孟，另有3例报告与药物无关的死亡病例。
结论：在真实世界临床场景中，对于其他治疗方案无法有效控制病情的肢端肥大症患者，培维索孟是一种高效且安全的治疗手段。