Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: Safety and efficacy evaluation from the German Pegvisomant Observational Study
Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: Safety and efficacy evaluation from the German Pegvisomant Observational Study
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DOI：
10.1530/eje.1.02312
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发表时间：
2007-01-01
影响因子：
5.8
通讯作者：
Strasburger, C. J.
中科院分区：
文献类型：
--
作者：
Schreiber, I.;Buchfelder, M.;Strasburger, C. J.
目的：GH 受体拮抗剂培维索孟是肢端肥大症的一种高效新治疗选择。德国培维索孟观察性研究（GPOS）旨在监测临床实践中培维索孟的长期安全性和有效性。设计：GPOS 是一项观察性、多中心、监测研究，包括非干预性数据收集。方法：在研究纳入的 229 名患者中，90.4% 曾接受过垂体手术，43.2% 接受过放射治疗，94.3% 曾接受过药物治疗肢端肥大症已停止，主要是由于 IGF-I 持续升高或副作用。意向治疗人群包括 177 名至少进行过一次基线后疗效测量的患者。 结果：IGF-I 水平从基线时正常上限的 1.75 +/- 0.91 倍下降至 6 个月访视时的 1.05 +/- 0.62，12 个月访视时的 0.96 +/- 0.60，并在 24 个月后降至 0.89 +/- 0.41 倍。月（P < 0.0001）。培维索孟治疗的平均持续时间为 51.8 +/- 35.8 周（中位数 = 51.9 周）。中位剂量为 15.0 mg/天时，IGF-I 在 6 个月时正常化率为 64.4%，在 12 个月时为 70.99%，在 24 个月时为 76.3%。 6 个月后空腹血糖水平从 114.4 +/- 45.9 改善至 101.5 +/- 42.8 mg/dl (P < 0.01)，12 个月后改善至 100.6 +/- 33.2 mg/ml (P < 0.01)。通过特定体征和症状评分衡量的一般身体状况显着改善。发生率 > 1% 的不良事件包括 7.4% 的注射部位反应、5.2% 的肝酶升高（> 正常值的 3 倍）（3.1% 在继续治疗期间自发恢复正常）、5.2% 的垂体肿瘤体积增加（3.1% 得到验证）和 1.7% 的头痛。结论：培维索孟总体耐受性良好，安全性与临床试验中报告的相似，可以有效减少不良事件的发生率。常规治疗难治性肢端肥大症患者的 IGF-I。
Objective: The GH receptor antagonist pegvisomant is a highly effective new treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS) was started to monitor long-term safety and efficacy of pegvisomant as prescribed in clinical practice.Design: GPOS is an observational, multi-center, surveillance study, which comprises non-interventional data collection.Methods: Of the 229 patients included in the study, 90.4% had previous pituitary surgery, 43.2% were treated by radiation therapy, and 94.3% had previous medical therapy for acromegaly that had been discontinued mainly due to persistent IGF-I elevation or side effects. The intention-to-treat population included 177 patients with at least one post-baseline efficacy measurement.Results: IGF-I levels decreased from 1.75 +/- 0.91-fold the upper limit of normal at baseline to 1.05 +/- 0.62 at the 6-month visit, 0.96 +/- 0.60 at the 12-month visit, and to 0.89 +/- 0.41-fold after 24 months (P < 0.0001). Mean duration of pegvisomant therapy was 51.8 +/- 35.8 weeks (median=51.9 weeks). IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0 mg/day, in 70.99% at 12 months, and in 76.3% at 24 months. Fasting glucose levels improved from 114.4 +/- 45.9 to 101.5 +/- 42.8 mg/dl after 6 months (P < 0.01) and to 100.6 +/- 33.2 mg/ml after 12 months (P < 0.01). General physical condition measured by specific signs and symptoms score improved significantly. Adverse events occurring in > 1% were injection site reactions in 7.4%, elevated liver enzymes (> 3 times of normal) in 5.2% (3.1% spontaneously normalized during continued treatment), reported increase of pituitary tumor volume in 5.2% (which was verified in 3.1%), and headache in 1.7%.Conclusions: Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials and can effectively reduce IGF-I in patients with acromegaly refractory to conventional therapy.