Departement de Rhumatologie, AP-HP, Hôpital Ambroise Paré, INSERM U1173, Laboratoire d'Excellence INFLAMEX, UFR Simone Veil, Versailles-Saint-Quentin University, 92100, Boulogne-Billancourt, France.
Schlosspark-Klinik University Medicine, Berlin, Germany.
Clin Rheumatol. 2017 Dec;36(12):2655-2665. doi: 10.1007/s10067-017-3788-1. Epub 2017 Aug 18.
This post hoc analysis of ACQUIRE (NCT00559585) explored the effect of baseline body mass index (BMI) on the pharmacokinetics of and clinical response to subcutaneous (SC) or intravenous (IV) abatacept in patients with rheumatoid arthritis (RA). ACQUIRE was a phase 3b, 6-month, double-blind, double-dummy study in which patients with RA were randomized (1:1) to SC (fixed - dose; 125 mg/week) or IV (weight-tiered; ~ 10 mg/kg/month) abatacept plus methotrexate. In this analysis, minimum abatacept plasma concentration (C) was measured at 3 and 6 months, and clinical remission over 6 months was assessed by Disease Activity Score 28 (C-reactive protein; DAS28 [CRP], < 2.6), Simplified Disease Activity Index (SDAI, ≤ 3.3), and Clinical Disease Activity Index (CDAI, ≤ 2.8). Data were stratified by baseline BMI (underweight/normal, < 25 kg/m; overweight, 25 to < 30 kg/m; obese, ≥ 30 kg/m) and administration route. Of the 1456/1457 patients for whom baseline BMIs were available, 526 (36%; SC 265, IV 261) patients were underweight/normal, 497 (34%; SC 249, IV 248) were overweight, and 433 (30%; SC 221, IV 212) were obese. Median C abatacept concentration was ≥ 10 μg/mL (efficacy threshold) at 3 and 6 months in > 90% of patients across BMI groups with both administration routes. DAS28 (CRP), SDAI, and CDAI remission rates at 6 months were similar across BMI groups and 95% confidence intervals overlapped at all time points in both separate and pooled SC/IV analyses. Therapeutic concentrations of abatacept and clinical remission rates using stringent criteria were similar across patient BMIs and administration routes.
这项 ACQUIRE(NCT00559585)的事后分析探讨了基线体重指数(BMI)对类风湿关节炎(RA)患者皮下(SC)或静脉内(IV)阿巴西普药代动力学和临床反应的影响。ACQUIRE 是一项为期 6 个月的 3b 期、双盲、双模拟研究,其中 RA 患者按 1:1 随机分为 SC(固定剂量;125mg/周)或 IV(体重分层;约 10mg/kg/月)阿巴西普加甲氨蝶呤。在这项分析中,在 3 个月和 6 个月时测量最低阿巴西普血浆浓度(C),并通过疾病活动评分 28(C 反应蛋白;DAS28[CRP],<2.6)、简化疾病活动指数(SDAI,≤3.3)和临床疾病活动指数(CDAI,≤2.8)评估 6 个月时的临床缓解。根据基线 BMI(体重不足/正常,<25kg/m;超重,25 至<30kg/m;肥胖,≥30kg/m)和给药途径对数据进行分层。在可获得基线 BMI 的 1456/1457 名患者中,526 名(36%;SC265,IV261)患者体重不足/正常,497 名(34%;SC249,IV248)超重,433 名(30%;SC221,IV212)肥胖。在两种给药途径的所有 BMI 组中,90%以上的患者在 3 个月和 6 个月时阿巴西普的中位浓度均≥10μg/mL(疗效阈值)。在 6 个月时,DAS28(CRP)、SDAI 和 CDAI 缓解率在 BMI 组之间相似,并且在单独和汇总的 SC/IV 分析中,所有时间点的 95%置信区间均重叠。使用严格标准的阿巴西普治疗浓度和临床缓解率在患者 BMI 和给药途径之间相似。