PURPOSES Pasireotide is the first medical therapy officially approved for adult patients with Cushing's disease (CD) experiencing failure of pituitary surgery or not candidates for surgery. The current study aimed at investigating pasireotide effects on clinical picture and metabolic profile in patients enrolled in the phase III CSOM230B2305 trial at Naples center. In addition, the current study focused on safety issues encountered during the study, detailing the management of the different adverse events associated with the treatment with pasireotide in Naples center. METHODS Fourteen patients entered the study; eight patients, receiving pasireotide for at least 6 months, were considered for the efficacy analysis, whereas the entire cohort of 14 patients was considered for the safety analysis. RESULTS Full or partial disease control was obtained in 85.7% of patients, according to a "per-protocol" methodology analysis, and in 42.9% of patients, according to an "intention-to-treat" methodology analysis, after 12 months of treatment. A relevant improvement in clinical signs and symptoms, mainly in facial rubor, supraclavicular fat pad, bruising, hirsutism, and muscle strength was observed; body weight, body mass index, and waist circumference significantly reduced, and a slight non-significant reduction was observed in the prevalence of visceral obesity, hypercholesterolemia, and hypertriglyceridemia. Deterioration of glucose metabolism represented the most common adverse event, occurring in 71.4% of patients, and requiring a dietary regimen as first step, metformin therapy and/or long-acting insulin as second step, and short-acting insulin, as third step; no patients discontinued treatment for hyperglycaemia. Additional adverse events of interest were nausea (21.4%), and vomiting (14.3%), spontaneously resolved in few weeks or some months, except in one patient unsuccessfully treated with metoclopramide and ondansetron, and diarrhoea (14.3%), improved with loperamide treatment. Millimetric gallstones and biliary sludge (7.1%) were managed with ursodeoxycholic acid, inducing lithiasis and biliary sludge resolution, whereas hypocortisolism-related adverse events (7.1%) were resolved with a reduction in the pasireotide dose. CONCLUSIONS The current study on a limited series of patients contributes to confirm that pasireotide may be considered a valid option for treatment of patients with CD, although it requires an appropriate management of adverse events, especially hyperglycaemia.

中文翻译：

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Pasireotide在库欣病中的治疗：在单个中心的经验中，长期治疗对临床表现和代谢特征以及不良事件管理的影响。

目的Pasireotide是第一种被正式批准用于垂体手术失败或不适合手术的成年库欣病（CD）的成年患者的医学疗法。本研究旨在调查那不勒斯中心进行的III期CSOM230B2305临床试验的患者中帕西瑞肽对临床影像和代谢谱的影响。此外，当前的研究集中在研究过程中遇到的安全性问题上，详细介绍了在那不勒斯中心与帕瑞肽治疗相关的各种不良事件的管理。方法14例患者进入研究。8例接受帕瑞肽治疗至少6个月的患者被视为进行疗效分析，而14例患者的整个队列被视为进行安全性分析。结果治疗12个月后，根据“按方案”方法分析获得了85.7％的患者完全或部分疾病控制，根据“意向治疗”方法分析获得了42.9％的患者。观察到临床症状和体征有相应的改善，主要是在脸部红疹，锁骨上脂肪垫，瘀伤，多毛症和肌肉力量方面。体重，体重指数和腰围明显减少，内脏肥胖，高胆固醇血症和高甘油三酯血症的患病率略有下降，但无明显下降。葡萄糖代谢恶化是最常见的不良事件，发生在71.4％的患者中，第一步需要饮食方案，第二步需要二甲双胍治疗和/或长效胰岛素，第三步是短效胰岛素；没有患者因高血糖而终止治疗。其他令人关注的不良事件是恶心（21.4％）和呕吐（14.3％），在数周或数月内自发缓解，但一名接受甲氧氯普胺和恩丹西酮治疗失败的患者和腹泻（14.3％）通过洛哌丁胺治疗得到改善的患者除外。用熊去氧胆酸处理胆结石和胆汁淤泥（7.1％），可导致结石症和胆道淤泥消退，而皮质醇缺乏相关的不良事件（7.1％）则可通过减少帕雷肽的剂量解决。结论当前对一系列患者的研究有助于证实，尽管需要对不良事件进行适当的管理，但帕西肽可以作为治疗CD患者的有效选择，