Department of Development and Regeneration, Neuro-musculo-skeletal Research Unit, KU Leuven, Belgium.
Clin Exp Rheumatol. 2014 Jul-Aug;32(4):553-62. Epub 2014 Jul 8.
To assess the safety and efficacy of intravenous (IV) abatacept plus methotrexate (MTX) over 7 years, the longest observational period to date, in patients with established rheumatoid arthritis (RA) and an inadequate response to MTX.
Patients randomised to IV abatacept (10 or 2 mg/kg) or placebo, plus MTX, during the 1-year double-blind (DB) period of a Phase 2b study could enter the long-term extension (LTE) and receive IV abatacept 10 mg/kg monthly. Safety was assessed in patients who received ≥1 dose of abatacept; efficacy was assessed in patients originally randomised to 10 mg/kg abatacept (as-observed data).
A total of 219 patients entered the LTE; 114 (52.1%) completed 7 years of treatment with abatacept plus MTX. Cumulative (DB + LTE) incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 17.6, 3.2, 1.8, and 1.2/100 patient-years, respectively. Safety was consistent between the DB (n=220) and cumulative (n=287) periods. Improvements in American College of Rheumatology responses, disease activity, and normalisation of physical function and health-related quality of life were maintained over time. Approximately 80% of patients who achieved low disease activity or normalised modified Health Assessment Questionnaire scores at Year 1, and who remained in the study, sustained these responses in each subsequent year.
IV abatacept in combination with MTX demonstrated consistent safety and sustained efficacy over 7 years in MTX inadequate responders with established RA. Furthermore, some patients demonstrated a normalisation of physical function and health-related quality of life that was sustained over time.
评估静脉注射（IV）阿巴西普联合甲氨蝶呤（MTX）在已确诊的类风湿关节炎（RA）患者中的安全性和疗效，这些患者对 MTX 反应不足，且这是迄今为止最长的观察期。
在一项 2b 期研究的 1 年双盲（DB）期间，随机接受 IV 阿巴西普（10 或 2 mg/kg）或安慰剂联合 MTX 治疗的患者可进入长期扩展（LTE）期，并接受每月 10 mg/kg 的 IV 阿巴西普治疗。安全性评估接受了至少 1 剂阿巴西普的患者；疗效评估最初随机接受 10 mg/kg 阿巴西普的患者（观察数据）。
共有 219 名患者进入 LTE；114 名（52.1%）患者完成了 7 年的阿巴西普联合 MTX 治疗。严重不良事件、严重感染、恶性肿瘤和自身免疫事件的累积（DB+LTE）发生率分别为 17.6、3.2、1.8 和 1.2/100 患者年。DB（n=220）和累积（n=287）期间的安全性一致。美国风湿病学会（ACR）反应、疾病活动度以及身体功能和健康相关生活质量的正常化改善随时间推移而保持。大约 80%的患者在第 1 年达到低疾病活动度或正常化的改良健康评估问卷（HAQ）评分，且在研究中持续存在这些反应，在随后的每年都保持这些反应。
在对 MTX 反应不足的已确诊 RA 患者中，阿巴西普联合 MTX 静脉注射治疗 7 年显示出一致的安全性和持续疗效。此外，一些患者表现出身体功能和健康相关生活质量的正常化，且随时间推移保持稳定。
