对每日一次给予双释放氢化可的松替代治疗的肾上腺皮质功能减退症患者进行长期安全性的前瞻性评估。
Prospective evaluation of long-term safety of dual-release hydrocortisone replacement administered once daily in patients with adrenal insufficiency.
机构信息
Department of EndocrinologySahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma IncorporatedDepartment of EndocrinologySkånes University Hospital, SE-205 02 Malmö, SwedenDepartment of Public Health and Clinical MedicineUmeå University, SE-901 87 Umeå, SwedenSection of EndocrinologyDepartment of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 83 Linköping, SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMölndal, Sweden.
Department of EndocrinologySahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma IncorporatedDepartment of EndocrinologySkånes University Hospital, SE-205 02 Malmö, SwedenDepartment of Public Health and Clinical MedicineUmeå University, SE-901 87 Umeå, SwedenSection of EndocrinologyDepartment of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 83 Linköping, SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMölndal, SwedenDepartment of EndocrinologySahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma IncorporatedDepartment of EndocrinologySkånes University Hospital, SE-205 02 Malmö, SwedenDepartment of Public Health and Clinical MedicineUmeå University, SE-901 87 Umeå, SwedenSection of EndocrinologyDepartment of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, SE-581 83 Linköping, SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMölndal, Sweden.
出版信息
Eur J Endocrinol. 2014 Sep;171(3):369-77. doi: 10.1530/EJE-14-0327. Epub 2014 Jun 18.
OBJECTIVE
The objective was to assess the long-term safety profile of dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI).
DESIGN
Randomised, open-label, crossover trial of DR-HC or thrice-daily hydrocortisone for 3 months each (stage 1) followed by two consecutive, prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months (stage 3) at five university clinics in Sweden.
METHODS
Sixty-four adults with primary AI started stage 1, and an additional 16 entered stage 3. Patients received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and intercurrent illness (self-reported hydrocortisone use during illness).
RESULTS
In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 were not related to the cortisol exposure-time profile. The percentage of patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with thrice-daily hydrocortisone) decreased during stage 2, when all patients received DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious AEs/100 patient-years of DR-HC exposure.
CONCLUSIONS
This long-term prospective trial is the first to document the safety of DR-HC in patients with primary AI and demonstrates that such treatment is well tolerated during 24 consecutive months of therapy.
目的
评估双释放氢化可的松（DR-HC）在肾上腺功能不全（AI）患者中的长期安全性概况。
设计
在瑞典的五所大学诊所进行了为期 3 个月的 DR-HC 或每日三次氢化可的松（DR-HC 或每日三次氢化可的松）的随机、开放标签、交叉试验（第 1 阶段），随后进行了两项连续的、前瞻性、开放标签研究，分别为 6 个月（第 2 阶段）和 18 个月（第 3 阶段）。
方法
64 名原发性 AI 成人开始第 1 阶段，另外 16 名成人进入第 3 阶段。患者接受 DR-HC 20-40mg 每日一次和氢化可的松 20-40mg 分为每日三次剂量（仅第 1 阶段）。主要观察指标是不良事件（AE）和并发疾病（自我报告的疾病期间使用氢化可的松）。
结果
在第 1 阶段，患者使用 DR-HC 时有中位数为 1.5（范围为 1-9）次并发疾病事件，使用每日三次氢化可的松时有 1.0（1-8）次。第 1 阶段期间的 AE 与皮质醇暴露时间曲线无关。第 1 阶段有 1 项或多项 AE 的患者比例（DR-HC 为 73.4%；每日三次氢化可的松为 65.6%）在第 2 阶段（所有患者均接受 DR-HC）时下降，在第 2 阶段（第 1 个 3 个月时为 51%；第 2 个 3 个月时为 54%）。在第 1-3 阶段的组合中，19 名患者经历了 27 次严重 AE，相当于 18.6 次严重 AE/DR-HC 暴露 100 患者年。
结论
这是第一项在原发性 AI 患者中记录 DR-HC 安全性的长期前瞻性试验，证明在 24 个月的连续治疗中，这种治疗耐受性良好。
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