Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis
Targeting pathophysiological rhythms: prednisone chronotherapy shows sustained efficacy in rheumatoid arthritis
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DOI：
10.1136/ard.2009.126888
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发表时间：
2010-07-01
影响因子：
27.4
通讯作者：
Alten, Rieke
中科院分区：
文献类型：
--
作者：
Buttgereit, Frank;Doering, Gisela;Alten, Rieke
这项为期9个月的类风湿关节炎中泼尼松昼夜节律给药的开放标签扩展研究（CAPRA 1）调查了泼尼松时间疗法与一种新的修改释放（MR）泼尼松长达12个月的长期安全性和有效性。方法：288例类风湿性关节炎患者最初被随机分配到MR或立即释放（IR）强的松组，249例在9个月的开放标签延长期中继续接受强的松时间治疗（2- 10mg /天）。评估关节晨僵持续时间（MS）、疾病活动度评分（DAS28）、美国风湿病学会（ACR20）反应和血浆白细胞介素6 （IL-6）水平。根据不良事件报告和实验室调查分析安全性。结果在为期3个月的双盲期，MR组患者的MS降低了33.1%，而IR组没有观察到任何变化。治疗6个月后，IR/MR组MS降低了54%，MR/MR组MS降低了56%。12个月后MS降低45% （IR/MR组）和55% （MR/MR组）。MR治疗后血浆IL-6水平下降。DAS28分别由5.8降至4.8 （MR/MR组）和4.9 （IR/MR组）。根据ACR20标准，完成12个月研究的219名患者中有37%获得改善。不良事件与已知的低剂量强的松没有区别。结论MR片联合强的松时间疗法安全性好，耐受性好，持续改善，低剂量糖皮质激素治疗至少12个月的获益风险比更好。
Objective This 9-month open-label extension of the Circadian Administration of Prednisone in Rheumatoid Arthritis Study (CAPRA 1) investigated the long-term safety and efficacy of prednisone chronotherapy with a novel modified-release (MR) prednisone for up to 12 months.Methods Of 288 patients with rheumatoid arthritis originally randomised to MR or immediate-release (IR) prednisone, 249 continued with prednisone chronotherapy (2-10 mg/day) in the 9-month open-label extension. Duration of morning stiffness of the joints (MS), disease activity scores (DAS28), American College of Rheumatology (ACR20) responses and plasma levels of interleukin 6 (IL-6) were assessed. Safety was analysed from adverse event reports and laboratory investigations.Results During the 3-month double-blind phase, patients in the MR group achieved a reduction in MS of 33.1% while no change was observed in the IR group. After 6 months of treatment, MS was reduced in the IR/MR group by 54% and in the MR/MR group by 56%. MS reduction after 12 months was 45% (IR/MR group) and 55% (MR/MR group). Plasma levels of IL-6 declined on MR treatment. DAS28 was reduced from 5.8 to 4.8 (MR/MR group) and 4.9 (IR/MR group), respectively. 37% of the 219 patients who completed the 12-month study achieved improvement according to the ACR20 criteria. Adverse events did not differ from the known profile of low-dose prednisone.Conclusions Prednisone chronotherapy with the MR tablet was safe and well tolerated and provided a sustained improvement which resulted in a better benefit to risk ratio of low-dose glucocorticoid treatment for at least 12 months.