Immunogenicity, Safety, and Efficacy of Abatacept Administered Subcutaneously With or Without Background Methotrexate in Patients With Rheumatoid Arthritis: Results From a Phase III, International, Multicenter, Parallel-Arm, Open-Label Study
Immunogenicity, Safety, and Efficacy of Abatacept Administered Subcutaneously With or Without Background Methotrexate in Patients With Rheumatoid Arthritis: Results From a Phase III, International, Multicenter, Parallel-Arm, Open-Label Study
复制标题
类风湿性关节炎患者皮下注射阿帕他赛与或不注射甲氨蝶呤的免疫原性、安全性和疗效： 一项 III 期、国际、多中心、平行臂、开放标签研究的结果
DOI：
10.1002/acr.21876
复制
发表时间：
2013-05-01
影响因子：
4.7
通讯作者：
Corbo, Michael
中科院分区：
文献类型：
--
作者：
Nash, Peter;Nayiager, Sauithree;Corbo, Michael
目的评价甲氨蝶呤（MTX）对阿巴西普皮下注射（SC）免疫原性的影响，并评价其安全性和有效性。方法本III期开放标签研究包括4个月的短期（ST）期和正在进行的长期扩展（LTE）期。将风湿性关节炎患者分层，接受SC阿巴西普（125 mg/周）与（联合）或不与MTX（单药治疗），无静脉负荷剂量;接受单药治疗的患者可在LTE期间添加MTX。评估免疫原性（抗阿巴西普抗体阳性患者的百分比）。报告了ST和LTE期数据，包括LTE第14个月的疗效和LTE第20个月的安全性。结果100例入组患者中有96例完成了ST期; 3.9%（联合治疗）和4.1%（单药治疗）的患者出现一过性免疫原性，4个月时无患者抗体阳性。3.9%（联合用药）和6.1%（单药治疗）的患者报告了严重不良事件（SAE）; 5.9%（联合用药）和8.2%（单药治疗）的患者发生了SC注射反应，强度均为轻度。第4个月时，平均28关节疾病活动评分（DAS 28）变化为1.67（95%置信区间[95% CI] 2.06，1.28;联合治疗）和1.94（95% CI 2.46，1.42;单药治疗）。90例患者入组并在LTE阶段接受治疗; 83.3%（75/90）的患者在第24个月时仍在接受治疗。1例LTE治疗患者（1.1%）发生免疫原性，14.4%的患者发生SAE，未报告SC注射反应。对于进入LTE阶段的患者，第18个月时DAS 28较基线的平均变化为1.84（95% CI 2.23，1.34;联合治疗）和2.86（95% CI 3.46，2.27;单药治疗）。结论阿巴西普皮下注射无论是否联合MTX均未引起与安全性或有效性丧失相关的免疫原性。
Objective To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy. Methods This phase III, open-label study had a 4-month short-term (ST) period and an ongoing long-term extension (LTE) period. Rheumatoid arthritis patients were stratified to receive SC abatacept (125 mg/week) with (combination) or without MTX (monotherapy), with no intravenous loading dose; patients receiving monotherapy could add MTX in the LTE period. Immunogenicity (percentage of anti-abatacept antibodypositive patients) was assessed. ST and LTE period data are reported, including efficacy through LTE month 14 and safety through LTE month 20. Results Ninety-six of 100 enrolled patients completed the ST period; 3.9% (combination) and 4.1% of patients (monotherapy) developed transient immunogenicity, and no patients were antibody positive at month 4. Serious adverse events (SAEs) were reported in 3.9% (combination) and 6.1% of patients (monotherapy); 5.9% (combination) and 8.2% of patients (monotherapy) experienced SC injection reactions, and all were mild in intensity. Mean 28-joint Disease Activity Score (DAS28) changes were 1.67 (95% confidence interval [95% CI] 2.06, 1.28; combination) and 1.94 (95% CI 2.46, 1.42; monotherapy) at month 4. Ninety patients entered and were treated in the LTE period; 83.3% (75 of 90) remained ongoing at month 24. One LTE-treated patient (1.1%) developed immunogenicity, 14.4% of patients experienced SAEs, and no SC injection reactions were reported. For patients entering the LTE period, mean DAS28 changes from baseline were 1.84 (95% CI 2.23, 1.34; combination) and 2.86 (95% CI 3.46, 2.27; monotherapy) at month 18. Conclusion SC abatacept did not elicit immunogenicity associated with loss of safety or efficacy, either with or without MTX.