Pincus Theodore, Cutolo Maurizio
Rush University, Medical Center, Chicago, Ill., USA.
Neuroimmunomodulation. 2015;22(1-2):46-50. doi: 10.1159/000362734. Epub 2014 Sep 12.
Twelve clinical trials have documented that prednisone or prednisolone in doses of 10 mg/day or less is efficacious to improve function, maintain status and/or slow radiographic progression in patients with rheumatoid arthritis (RA). An early trial reported by de Andrade et al. [Ann Rheum Dis 1964;23:158-162] in 1964 indicated that 5 mg of prednisolone at night was preferred to 5 mg of prednisone in the morning. Harris et al. [J Rheumatol 1983;10:713-721] documented the efficacy of 5 mg/day of prednisone in a non-double-blind trial in 1983. Two important trials in the 1990s by Kirwan [N Engl J Med 1995;333:142-146] using 7.5 mg/day, and the COBRA study by Boers et al. [Lancet 1997;350:309-318] with step-down from 60 mg rapidly tapered to 5 mg/day led to strong advocacy of low-dose glucocorticoids. In 2002, the first Utrecht Study [Ann Intern Med 2002;136:1-12] indicated that 10 mg/day prednisone slowed radiographic progression, a finding confirmed and extended in 2005 by Svensson et al. [Arthritis Rheum 2005;52:3360-3370] with 7.5 mg/day, and Wassenberg et al. [Arthritis Rheum 2005;52:3371-3380] with 5 mg/day of prednisolone. In 2008, Buttgereit et al. [Lancet 2008;371:205-214] reported CAPRA-1, which documented that modified-release prednisone or prednisolone taken at bedtime led to lower morning stiffness and IL-6 levels compared to usual morning prednisone. In 2009, Pincus et al. [Ann Rheum Dis 2009;68:1715-1720] reported a withdrawal clinical trial, in which patients who took 3 mg/day were gradually withdrawn to placebo, and dropped out at a significantly higher rate than control patients who were 'withdrawn' to prednisone. In 2012, a second Utrecht Study [Ann Intern Med 2012;156:329-339], CAMERA-II, documented that 10 mg of prednisone added to a 'treat-to-target' strategy with methotrexate provided incremental slowing of radiographic progression. An Italian study of patients with early RA who received step-up disease-modifying antirheumatic drug therapy over 2 years plus prednisolone or not indicated higher rates of clinical remission and sustained remission associated with 7.5 mg/day of prednisolone [Arthritis Res Ther 2012; 14:R112]. The CAPRA-2 trial [Ann Rheum Dis 2013;72:204-210] documented that modified-release nighttime prednisone or prednisolone was significantly more efficacious than placebo. Taken together, these 12 clinical trials indicate that low-dose glucocorticoids prednisone or prednisolone provides symptomatic relief, improved functional status and slowing of radiographic progression for patients with RA. © 2014 S. Karger AG, Basel.
12项临床试验已证明，剂量为10毫克/天或更低的泼尼松或泼尼松龙可有效改善类风湿关节炎（RA）患者的功能、维持病情稳定和/或减缓影像学进展。1964年，de Andrade等人[《风湿病年鉴》1964年；23:158 - 162]报告的一项早期试验表明，夜间服用5毫克泼尼松龙比早晨服用5毫克泼尼松更可取。1983年，Harris等人[《风湿病学杂志》1983年；10:713 - 721]在一项非双盲试验中证明了5毫克/天泼尼松的疗效。20世纪90年代，Kirwan[《新英格兰医学杂志》1995年；333:142 - 146]进行的两项重要试验使用了7.5毫克/天，以及Boers等人[《柳叶刀》1997年；350:309 - 318]的COBRA研究从60毫克迅速递减至5毫克/天，导致了对低剂量糖皮质激素的大力倡导。2002年，第一项乌得勒支研究[《内科学年鉴》2002年；136:1 - 12]表明，10毫克/天泼尼松可减缓影像学进展，2005年，Svensson等人[《关节炎与风湿病》2005年；52:3360 - 3370]使用7.5毫克/天以及Wassenberg等人[《关节炎与风湿病》2005年；52:3371 - 3380]使用5毫克/天泼尼松龙证实并扩展了这一发现。2008年，Buttgereit等人[《柳叶刀》2008年；371:205 - 214]报告了CAPRA - 1，该研究证明与早晨常规服用泼尼松相比，睡前服用缓释泼尼松或泼尼松龙可降低晨僵和白细胞介素 - 6水平。2009年，Pincus等人[《风湿病年鉴》2009年；68:1715 - 1720]报告了一项撤药临床试验，其中服用3毫克/天的患者逐渐撤药至安慰剂，其退出率显著高于“撤药”至泼尼松的对照患者。2012年，第二项乌得勒支研究[《内科学年鉴》2012年；156:329 - 339]，即CAMERA-II，证明在甲氨蝶呤“达标治疗”策略基础上加用10毫克泼尼松可进一步减缓影像学进展。一项针对早期RA患者的意大利研究表明，在2年多的时间里接受逐步升级的改善病情抗风湿药物治疗并加用或不加用泼尼松龙，与7.5毫克/天泼尼松龙相关的临床缓解率和持续缓解率更高[《关节炎研究与治疗》2012年；14:R112]。CAPRA - 2试验[《风湿病年鉴》2013年；72:204 - 210]证明，夜间服用缓释泼尼松或泼尼松龙比安慰剂显著更有效。综上所述，这12项临床试验表明，低剂量糖皮质激素泼尼松或泼尼松龙可为RA患者提供症状缓解、改善功能状态并减缓影像学进展。© 2014 S. Karger AG，巴塞尔。
