库欣病治疗效果的系统评价和荟萃分析。
Effectiveness of Medical Treatment of Cushing's Disease: A Systematic Review and Meta-Analysis.
机构信息
University of Cologne, Faculty of Medicine and University Hospital of Cologne, Institute of Health Economics and Clinical Epidemiology, Cologne, Germany.
Medical School, Federal University of Minas Gerais, Belo Horizonte, Brazil.
出版信息
Front Endocrinol (Lausanne). 2021 Sep 17;12:732240. doi: 10.3389/fendo.2021.732240. eCollection 2021.
OBJECTIVE
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).
METHODS
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 (., pre- and post-intervention). Random meta-analyses for the proportion of CD control and AE were conducted.
RESULTS
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 . 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.
CONCLUSION
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.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, identifier CRD42020205567.
目的
本系统评价的目的是评估培高利特、卡麦角林、酮康唑、左酮康唑、美替拉酮、奥昔拉定和替莫唑胺治疗库欣病（CD）的疗效和安全性。
方法
主要结局指标为 CD 控制率、不良事件（AE）和尿游离皮质醇减少率。采用 Embase、Medline 和 CENTRAL 进行搜索策略。独立审查员评估研究的合格性、提取数据并评估偏倚风险。使用标准化均数差（SMD）和 95%置信区间（CI）计算连续数据（., 干预前和干预后）。对 CD 控制率和 AE 的比例进行随机荟萃分析。
结果
纳入了 29 项对照和非对照研究。没有培美曲塞和左酮康唑的研究，也只有一项奥昔拉定的研究符合纳入标准。卡麦角林的 CD 控制比例的荟萃分析为 35%（95%CI：27-43%，6 项研究，141 名参与者），培高利特为 44%（95%CI：25-35%，8 项研究，522 名参与者），酮康唑为 41%（95%CI：36-46%，6 项研究，450 名参与者），美替拉酮为 66%（95%CI：46-87%，4 项研究，66 名参与者），奥昔拉定为 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. 酮康唑），但在 CD 控制方面未观察到统计学差异（RR：0.53，95%CI：0.15 至 1.87，14 名参与者，极低确定性证据）。与培高利特相关的最常见 AE 是高血糖，卡麦角林和美替拉酮相关的头晕和恶心，酮康唑相关的转氨酶升高。
结论
由于缺乏对照研究，无法确定一种药物优于另一种药物，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的治疗方法疗效有限且耐受性差，因此应研究新的治疗选择。
系统评价注册
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567，标识符 CRD42020205567。
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