The Efficacy and Safety of Abatacept in Patients With Non-Life-Threatening Manifestations of Systemic Lupus Erythematosus Results of a Twelve-Month, Multicenter, Exploratory, Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial
The Efficacy and Safety of Abatacept in Patients With Non-Life-Threatening Manifestations of Systemic Lupus Erythematosus Results of a Twelve-Month, Multicenter, Exploratory, Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial
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DOI：
10.1002/art.27601
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发表时间：
2010-10-01
影响因子：
--
通讯作者：
Nash, P.
中科院分区：
文献类型：
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作者：
Merrill, J. T.;Burgos-Vargas, R.;Nash, P.
客观的。旨在评估阿巴西普治疗非危及生命的系统性红斑狼疮 (SLE) 和多关节炎、盘状病变或胸膜炎和/或心包炎患者的疗效。方法。在一项为期 12 个月、多中心、探索性、IIb 期随机、双盲、安慰剂对照试验中，患有多关节炎、盘状病变或胸膜炎和/或心包炎的 SLE 患者以 2:1 的比例随机接受阿巴西普（类似于 10 mg/kg 体重）或安慰剂。给予泼尼松（30 mg/天或同等量）1个月，然后逐渐减少剂量。主要终点是类固醇逐渐减量开始后，根据不列颠群岛狼疮评估组 (BILAG) 指数 A/B 评分出现新发红斑（判定）的患者比例。结果。共有 118 名患者被随机分配接受阿巴西普治疗，57 名患者接受安慰剂治疗。两组的基线特征相似。阿巴西普组 12 个月内新发 BILAG A/B 发作的比例为 79.7%（95% 置信区间 [95% CI] 72.4, 86.9），安慰剂组为 82.5%（95% CI 72.6, 92.3）（治疗差异 -3.5 [95% CI -15.3, 8.3]）。其他预先指定的耀斑终点未得到满足。在事后分析中，阿巴西普治疗和安慰剂治疗患者出现 BILAG A 发作的比例分别为 40.7% (95% CI 31.8, 49.5) 和 54.4% (95% CI 41.5, 67.3)，医生评估的发作比例分别为 63.6% (95% CI 54.9, 72.2) 和82.5% (95% CI 72.6, 92.3)；多关节炎组的治疗差异最大。预先指定的探索性患者报告结果（简表 36 健康调查、睡眠问题、疲劳）证明了阿巴西普的治疗效果。阿巴西普组和安慰剂组的不良事件 (AE) 频率相当（90.9% 对 91.5%），但阿巴西普组的严重不良事件 (SAE) 较高（19.8% 对 6.8%）。大多数 SAE 是单一的、与疾病相关的事件，发生在研究的前 6 个月（包括类固醇逐渐减量期）。结论。尽管本研究未达到主要/次要终点，但某些探索性措施的改进表明阿巴西普对非危及生命的 SLE 患者具有一定疗效。 SAE 发生率的增加需要进一步评估。
Objective. To evaluate abatacept therapy in patients with non-life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis.Methods. In a 12-month, multicenter, exploratory, phase IIb randomized, double-blind, placebo-controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (similar to 10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper.Results. A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference -3.5 [95% CI -15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period).Conclusion. Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non-life-threatening manifestations of SLE. The increased rate of SAEs requires further assessment.