Hypothalamus-Pituitary-Adrenal Axis Function in Patients with Rheumatoid Arthritis Treated with Nighttime-Release Prednisone
Hypothalamus-Pituitary-Adrenal Axis Function in Patients with Rheumatoid Arthritis Treated with Nighttime-Release Prednisone
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DOI：
10.3899/jrheum.100051
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发表时间：
2010-10-01
影响因子：
3.9
通讯作者：
Buttgereit, Frank
中科院分区：
文献类型：
--
作者：
Alten, Rieke;Doering, Gisela;Buttgereit, Frank
Objective.作为风湿性关节炎泼尼松昼夜节律给药（CAPRA-1）研究的一部分，研究长期低剂量缓释（MR）泼尼松时辰疗法治疗类风湿关节炎（RA）对下丘脑-垂体-肾上腺（HPA）轴的影响。这包括3个月的活性对照期和9个月的MR泼尼松开放标签扩展期，包括既往接受泼尼松治疗的患者（临床Trials.gov编号NCT 00146640）。在3个时间点对28例患者进行促肾上腺皮质激素释放激素（CRH）检测：在研究前即释（IR）泼尼松基线时，在IR泼尼松或MR泼尼松3个月双盲期后，在MR泼尼松9个月开放标签扩展期后。皮质醇的变化进行了评估，并与个别患者的疗效和安全性数据进行了比较。增长（平均值）注射皮质激素后皮质醇血浆浓度的标准差（SD）在基线时IR泼尼松组为5.5（4.37）μ g/dl（n = 21），在12个月时MR泼尼松组为5.3（4.07）μ g/dl（n = 22）。正常/抑制/无应答反应的数量在治疗间无差异。从IR转换为MR泼尼松不影响反应，也没有长期治疗长达12个月的MR泼尼松。对于CRH试验低反应性患者，在MR泼尼松治疗前给予夜间释放泼尼松治疗，未观察到肾上腺损害恶化。在12个月的时间里，夜间释放的泼尼松治疗没有改变肾上腺皮质功能。我们推测，夜间释放泼尼松的时辰疗法可能会改善长期低剂量糖皮质激素治疗RA患者的疗效。（2010年8月1日首次发布; J Rheumol 2010;37：2025-31; doi：10.3899/jrheum.100051）
Objective. To investigate the effects of longterm low-dose chronotherapy with modified-release (MR) prednisone for rheumatoid arthritis (RA) on the hypothalamus-pituitary-adrenal (HPA) axis as part of the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-1) study. This consisted of a 3-month active-controlled phase and a 9-month open-label extension with MR prednisone including patients previously treated with prednisone (Clinical Trials.gov number NCT00146640).Methods. Corticotropin-releasing hormone (CRH) tests were performed on 28 patients at 3 time-points: at baseline on prestudy immediate-release (IR) prednisone, after the 3-month double-blind phase on either IR prednisone or MR prednisone, and after the 9-month open-label extension on MR prednisone. Changes of cortisol were assessed and compared to individual patients' efficacy and safety data.Results. The increase (mean. SD) of cortisol plasma concentrations after injection of corticorelin was 5.5 (4.37) mu g/dl on IR prednisone at baseline (n = 21) and 5.3 (4.07) mu g/dl on MR prednisone at 12 months (n = 22). Numbers of normal/suppressed/no response reactions did not differ among treatments. Switching from IR to MR prednisone did not influence responses, nor did longterm treatment of up to 12 months with MR prednisone. No worsening of adrenal impairment was observed on treatment with nighttime-release prednisone in patients with low responsiveness to CRH testing before the treatment with MR prednisone.Conclusion. Treatment with nighttime-release prednisone did not change adrenocortical function over 12 months. We presume that chronotherapy with this nighttime-release prednisone may improve the efficacy of longterm low-dose glucocorticoid treatment in patients with RA. (First Release August 1 2010; J Rheumatol 2010;37:2025-31; doi:10.3899/jrheum.100051)