The objective of this systematic review was to evaluate the effectiveness and safety of pasireotide, cabergoline, ketoconazole, levoketoconazole, metyrapone, osilodrostat, and temozolomide for the treatment of Cushing’s disease (CD).

The primary outcomes were the proportion of CD control, adverse events (AE), and reduction of urinary free cortisol. Search strategies were applied to Embase, Medline, and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Standardized mean difference was calculated with 95% confidence interval (CI) for continuous data (i.e., pre- and post-intervention). Random meta-analyses for the proportion of CD control and AE were conducted.

Twenty-nine controlled and non-controlled studies were included. No study with temozolomide and levoketoconazole and one study with osilodrostat fulfilled the inclusion criteria. The meta-analyses of proportion of CD control was 35% for cabergoline (95% CI: 27–43%, six studies, 141 participants), 44% for pasireotide (95% CI: 25–35%, eight studies, 522 participants), 41% for ketoconazole (95% CI: 36–46%, six studies, 450 participants), 66% for metyrapone (95% CI: 46–87%, four studies, 66 participants), and of 66.4% for osilodrostat (95% CI: 57.9, 74.3, 97 participants, one study). One study compared two different treatments (cabergoline vs. ketoconazole), and no statistical difference was observed in CD control (RR: 0.53, 95% CI: 0.15 to 1.87, 14 participants, very low certainty of evidence). The most frequent AE associated with pasireotide was hyperglycemia, dizziness and nausea with cabergoline and metyrapone, and elevated transaminases with ketoconazole.

The superiority of one drug over another could not be determined due to lack of controlled studies, but the proportion of disease control identified in our meta-analysis may support clinical decision. New therapeutic options should be investigated due to the limited efficacy and tolerability of the currently available medical treatment for patients with Cushing’s disease.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, identifier CRD42020205567.

本系统评价的目的是评估帕瑞肽、卡麦角林、酮康唑、左酮康唑、美替拉酮、奥司洛他和替莫唑胺治疗库欣病 (CD) 的有效性和安全性。

主要结果是 CD 控制的比例、不良事件 (AE) 和尿游离皮质醇的减少。搜索策略应用于 Embase、Medline 和 CENTRAL。独立评审员评估研究资格、提取数据并评估偏倚风险。连续数据的标准化平均差采用 95% 置信区间 (CI) (IE.，干预前和干预后）。对 CD 对照和 AE 的比例进行了随机荟萃分析。

包括 29 项对照和非对照研究。没有一项关于替莫唑胺和左酮康唑的研究和一项关于奥司洛他的研究符合纳入标准。卡麦角林的 CD 控制比例荟萃分析为 35%（95% CI：27-43%，6 项研究，141 名参与者），帕瑞肽为 44%（95% CI：25-35%，8 项研究，522 名参与者） )，酮康唑为 41%（95% CI：36-46%，六项研究，450 名参与者），美替拉酮为 66%（95% CI：46-87%，四项研究，66 名参与者），奥司洛他为 66.4% （95% CI：57.9、74.3、97 名参与者，一项研究）。一项研究比较了两种不同的治疗方法（卡麦角林对比. 酮康唑），在 CD 对照组中未观察到统计学差异（RR：0.53，95% CI：0.15 至 1.87，14 名参与者，证据质量非常低）。与帕瑞肽相关的最常见 AE 是卡麦角林和美替拉酮的高血糖、头晕和恶心，以及酮康唑的转氨酶升高。

由于缺乏对照研究，无法确定一种药物优于另一种药物的优势，但我们的荟萃分析中确定的疾病控制比例可能支持临床决策。由于目前对库欣病患者可用的药物治疗的有效性和耐受性有限，因此应研究新的治疗选择。

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, 标识符 CRD42020205567。