Department of Epidemiology & Data Science, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
Department of Epidemiology & Data Science, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
Ann Rheum Dis. 2023 Oct;82(10):1307-1314. doi: 10.1136/ard-2023-223977. Epub 2023 Aug 4.
The randomised placebo-controlled GLORIA (Glucocorticoid LOw-dose in RheumatoId Arthritis) trial evaluated the benefits and harms of prednisolone 5 mg/day added to standard care for 2 years in patients aged 65+ years with rheumatoid arthritis (RA). Here, we studied disease activity, flares and possible adrenal insufficiency after blinded withdrawal of study medication.
Per protocol, patients successfully completing the 2-year trial period linearly tapered and stopped blinded study medication in 3 months. We compared changes in disease activity after taper between treatment groups (one-sided testing). Secondary outcomes (two-sided tests) comprised disease flares (DAS28 (Disease Activity Score 28 joints) increase >0.6, open-label glucocorticoids or disease-modifying antirheumatic drug (DMARD) increase/switch after week 4 of tapering) and symptoms/signs of adrenal insufficiency. In a subset of patients from 3 Dutch centres, cortisol and ACTH were measured in spot serum samples after tapering.
191 patients were eligible; 36 met treatment-related flare criteria and were only included in the flare analysis. Mean (SD) DAS28 change at follow-up: 0.2 (1.0) in the prednisolone group (n=76) vs 0.0 (1.2) in placebo (n=79). Adjusted for baseline, the between-group difference in DAS28 increase was 0.16 (95% confidence limit -0.06, p=0.12). Flares occurred in 45% of prednisolone patients compared with 33% in placebo, relative risk (RR) 1.37 (95% CI 0.95 to 1.98; p=0.12). We found no evidence for adrenal insufficiency.
Tapering prednisolone moderately increases disease activity to the levels of the placebo group (mean still at low disease activity levels) and numerically increases the risk of flare without evidence for adrenal insufficiency. This suggests that withdrawal of low-dose prednisolone is feasible and safe after 2 years of administration.
GLORIA（糖皮质激素在老年类风湿关节炎中的低剂量）是一项随机安慰剂对照试验，评估了泼尼松龙 5mg/天联合标准治疗在 65 岁以上类风湿关节炎（RA）患者中使用 2 年的疗效和安全性。在这里，我们研究了在停止使用研究药物后盲法洗脱期内疾病活动度、发作和可能出现的肾上腺功能不全的情况。
根据方案，成功完成 2 年试验期的患者以线性方式逐渐减少并在 3 个月内停用盲法研究药物。我们比较了治疗组在减药期间疾病活动度的变化（单侧检验）。次要结局（双侧检验）包括疾病发作（DAS28（28 个关节疾病活动度评分）增加>0.6，在减药第 4 周后开放标签使用糖皮质激素或改变/添加改善病情抗风湿药物（DMARD））和肾上腺功能不全的症状/体征。在来自荷兰 3 个中心的患者亚组中，在减药后采集点血清样本测量皮质醇和 ACTH。
191 名患者符合条件；36 名患者符合与治疗相关的发作标准，仅纳入发作分析。随访时 DAS28 的平均（SD）变化：泼尼松龙组为 0.2（1.0）（n=76），安慰剂组为 0.0（1.2）（n=79）。调整基线后，两组间 DAS28 增加的差异为 0.16（95%置信区间 -0.06，p=0.12）。泼尼松龙组的发作率为 45%，安慰剂组为 33%，相对风险（RR）为 1.37（95%CI 0.95 至 1.98；p=0.12）。我们没有发现肾上腺功能不全的证据。
逐渐减少泼尼松龙的剂量会使疾病活动度适度增加到安慰剂组的水平（平均仍处于低疾病活动度水平），并在数值上增加发作的风险，但没有肾上腺功能不全的证据。这表明，在 2 年的治疗后，低剂量泼尼松龙的停药是可行和安全的。
