DataSheet_1_Ketoconazole as second-line treatment for Cushing’s disease after transsphenoidal surgery: systematic review and meta-analysis.pdf

IntroductionThe first-line treatment for Cushing’s disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response.
MethodsWe searched for articles that evaluated ketoconazole use in Cushing’s disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels.
ResultsAfter applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism.
ConclusionKetoconazole can be considered a safe and efficacious option for Cushing’s disease treatment after pituitary surgery.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).

引言
库欣病（Cushing’s disease）的一线治疗方案为经蝶窦垂体瘤切除术（transsphenoidal surgery for pituitary tumor resection）。尽管酮康唑（ketoconazole）用于该适应证的安全性与有效性数据有限，但仍被用作二线治疗药物。本荟萃分析（meta-analysis）旨在分析经蝶窦手术后将酮康唑作为二线治疗方案的患者的皮质醇增多症（hypercortisolism）控制情况，同时探究与治疗应答相关的其他临床及实验室指标。

方法
本研究检索了评估经蝶窦手术后使用酮康唑治疗库欣病的相关文献，检索策略应用于MEDLINE、EMBASE及SciELO数据库。由独立评审人员评估研究的纳入资格与质量，并提取皮质醇增多症控制情况及相关变量（包括治疗剂量、治疗时长及尿皮质醇水平）的数据。

结果
经排除标准筛选后，最终纳入10篇文献（1项前瞻性研究、9项回顾性研究，共计270例患者）进行完整数据分析。在报告的生化控制与未生化控制结果中，均未发现发表偏倚（分别为p=0.06与p=0.42）。270例患者中，151例（63%，95%置信区间95%CI 50-74%）实现皮质醇增多症的生化控制，61例（20%，95%置信区间95%CI 10-35%）未实现生化控制。荟萃回归分析显示，最终给药剂量、治疗时长及初始血清皮质醇水平均与皮质醇增多症的生化控制无相关性。

结论
酮康唑可被视为垂体手术后库欣病治疗的安全且有效的备选方案。

系统评价注册信息：https://www.crd.york.ac.uk/prospero/#searchadvanced，注册号CRD42022308041。