Merrill J T, Burgos-Vargas R, Westhovens R, Chalmers A, D'Cruz D, Wallace D J, Bae S C, Sigal L, Becker J-C, Kelly S, Raghupathi K, Li T, Peng Y, Kinaszczuk M, Nash P
Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Arthritis Rheum. 2010 Oct;62(10):3077-87. doi: 10.1002/art.27601.
To evaluate abatacept therapy in patients with non-life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis.
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 (∼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.
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).
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.
评估阿巴西普治疗非危及生命的系统性红斑狼疮（SLE）合并多关节炎、盘状红斑或胸膜炎和/或心包炎患者的疗效。
在一项为期12个月的多中心、探索性IIb期随机、双盲、安慰剂对照试验中，将患有多关节炎、盘状红斑或胸膜炎和/或心包炎的SLE患者按2:1的比例随机分组，分别接受阿巴西普（约10mg/kg体重）或安慰剂治疗。给予泼尼松（30mg/天或等效剂量）1个月，然后逐渐减量。主要终点是在类固醇减量开始后，根据不列颠群岛狼疮评估组（BILAG）指数A/B评分判定的新发病情活动的患者比例。
共有118例患者被随机分配接受阿巴西普治疗，57例接受安慰剂治疗。两组的基线特征相似。阿巴西普组12个月内新出现的BILAG A/B病情活动比例为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]）。其他预先设定的病情活动终点未达到。在事后分析中，阿巴西普治疗组和安慰剂治疗组出现BILAG A病情活动的患者比例分别为40.7%（95%CI 31.8,49.5）和54.4%（95%CI 41.5,67.3），医生评估的病情活动比例分别为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。预先设定的探索性患者报告结局（简明健康调查问卷、睡眠问题、疲劳）显示阿巴西普有治疗效果。阿巴西普组和安慰剂组的不良事件（AE）发生率相当（90.9%对91.5%），但阿巴西普组的严重不良事件（SAE）发生率更高（19.8对6.8%）。大多数SAE为单一的、与疾病相关的事件，发生在研究的前6个月（包括类固醇减量期）。
尽管本研究未达到主要/次要终点，但某些探索性指标的改善表明阿巴西普对SLE非危及生命表现的患者有一定疗效。SAE发生率的增加需要进一步评估。
