Subcutaneous Abatacept Versus Intravenous Abatacept A Phase IIIb Noninferiority Study in Patients With an Inadequate Response to Methotrexate
Subcutaneous Abatacept Versus Intravenous Abatacept A Phase IIIb Noninferiority Study in Patients With an Inadequate Response to Methotrexate
复制标题
DOI：
10.1002/art.30463
复制
发表时间：
2011-10-01
影响因子：
--
通讯作者：
Alten, R.
中科院分区：
文献类型：
--
作者：
Genovese, M. C.;Covarrubias, A.;Alten, R.
Objective.比较皮下注射（SC）和静脉注射（IV）阿巴西普的疗效和安全性。在这项IIIb期双盲、双模拟、6个月的研究中，患有类风湿性关节炎（RA）且对甲氨蝶呤应答不足的患者被随机分配在第1天和第8天接受125 mg阿巴西普SC，此后每周一次（加第1天的IV负荷剂量[类似于10 mg/kg]）或第1、15和29天的IV阿巴西普（类似于10 mg/kg）以及此后每4周。用于确定SC阿巴西普相对于IV阿巴西普的非劣效性的主要终点是在第6个月时每组中满足美国流变学会20%改善标准（实现ACR 20应答）的患者比例。其他疗效终点、免疫原性和安全性也进行了评估。在1，457名患者中，736名SC阿巴西普治疗患者中的693名（94.2%）和721名IV阿巴西普治疗患者中的676名（93.8%）完成了6个月。第6个月，76.0%（95%置信区间为72.9，79.2），SC阿巴西普治疗的患者为75.8%，（95%置信区间72.6，79.0），静脉注射阿巴西普治疗的患者达到ACR 20应答（组间估计差异0.3% [95%置信区间-4.2，4.8]），证实SC阿巴西普相对于IV阿巴西普的非劣效性。SC和IV阿巴西普治疗组之间ACR反应的发作和幅度以及疾病活动和身体功能改善相当。6个月内的不良事件（AE）和严重AE的比例在SC阿巴西普治疗组中分别为67.0%和4.2%，在IV阿巴西普治疗组中分别为65.2%和4.9%，两组之间严重感染、恶性肿瘤和自身免疫事件的频率相当。SC注射部位反应（大多数为轻度）发生在19例SC阿巴西普（IV安慰剂）治疗患者（2.6%）和18例IV阿巴西普（SC安慰剂）治疗患者（2.5%）中。阿巴西普诱导的抗体发生在1.1%的阿巴西普SC治疗患者和2.3%的阿巴西普IV治疗患者中。SC阿巴西普提供与IV阿巴西普相当的功效和安全性，具有低免疫原性和高保留率，与已建立的IV阿巴西普特征一致。注射部位反应的发生率较低。SC阿巴西普将为RA患者提供额外的治疗选择，例如替代给药途径。
Objective. To compare the efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept.Methods. In this phase IIIb double-blind, double-dummy, 6-month study, patients with rheumatoid arthritis (RA) and inadequate responses to methotrexate were randomized to receive 125 mg SC abatacept on days 1 and 8 and weekly thereafter (plus an IV loading dose [similar to 10 mg/kg] on day 1) or IV abatacept (similar to 10 mg/kg) on days 1, 15, and 29 and every 4 weeks thereafter. The primary end point for determining the noninferiority of SC abatacept to IV abatacept was the proportion of patients in each group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at month 6. Other efficacy end points, immunogenicity, and safety were also assessed.Results. Of 1,457 patients, 693 of 736 (94.2%) treated with SC abatacept and 676 of 721 (93.8%) treated with IV abatacept completed 6 months. At month 6, 76.0% (95% confidence interval 72.9, 79.2) of SC abatacept-treated patients versus 75.8% (95% confidence interval 72.6, 79.0) of IV abatacept-treated patients achieved an ACR20 response (estimated difference between groups 0.3% [95% confidence interval -4.2, 4.8]), confirming noninferiority of SC abatacept to IV abatacept. Onset and magnitude of ACR responses and disease activity and physical function improvements were comparable between the SC and IV abatacept-treated groups. The proportions of adverse events (AEs) and serious AEs over 6 months were 67.0% and 4.2%, respectively, in the SC abatacept-treated group and 65.2% and 4.9%, respectively, in the IV abatacept-treated group, with comparable frequencies of serious infections, malignancies, and autoimmune events between groups. SC injection site reactions (mostly mild) occurred in 19 SC abatacept (IV placebo)-treated patients (2.6%) and 18 IV abatacept (SC placebo)-treated patients (2.5%). Abatacept-induced antibodies occurred in 1.1% of SC abatacept-treated patients and 2.3% of IV abatacept-treated patients.Conclusion. SC abatacept provides efficacy and safety comparable with that of IV abatacept, with low immunogenicity and high retention rates, consistent with the established IV abatacept profile. Rates of injection site reactions were low. SC abatacept will provide additional treatment options, such as an alternative route of administration, for patients with RA.