Westhovens Rene, Kremer Joel M, Moreland Larry W, Emery Paul, Russell Anthony S, Li Tracy, Aranda Richard, Becker Jean-Claude, Qi Keqin, Dougados Maxime
Department of Rheumatology, KU Leuven, Herestraat 49, B 3000 Leuven, Belgium.
J Rheumatol. 2009 Apr;36(4):736-42. doi: 10.3899/jrheum.080813. Epub 2009 Feb 27.
To evaluate the safety and efficacy of abatacept plus methotrexate (MTX) over 5 years in patients with rheumatoid arthritis.
Patients were randomized to abatacept 10 or 2 mg/kg or placebo, plus MTX. Patients completing the 1-year, double-blind period entered the longterm extension, where all patients received a fixed dose of abatacept ~10 mg/kg. We describe safety analyses for all patients who received at least 1 dose of abatacept and efficacy analyses for the original ~10 mg/kg abatacept-treated group, over 5 years.
Of the 235 abatacept- or placebo-treated patients completing the double-blind period, 219 entered the longterm extension; 130 (59.4%) were continuing at Year 5. No unexpected safety events were observed during the longterm extension compared with the double-blind period. Incidence rates of adverse events (AE) and serious AE were 489.7 and 20.0/100 patient-years in Year 1 versus 374.9 and 18.9/100 patient-years in the cumulative period, respectively. Using exploratory analyses, improvements observed at Year 1 in the 10 mg/kg group were maintained at Year 5, as assessed by ACR responses (ACR20=77.1% vs 82.7%; ACR50=53.0% vs 65.4%; ACR70=28.9% vs 40.4% at Years 1 and 5, respectively) and disease activity (Low Disease Activity State=48.2% vs 58.5%; Disease Activity Score-28-defined remission=25.3% vs 45.3% at Years 1 and 5, respectively).
Abatacept maintained the efficacy observed at Year 1 over 5 years of treatment, and demonstrated consistent safety and tolerability. These data, along with relatively high retention rates, support the longterm clinical benefit provided by selective T cell costimulation modulation.
ClinicalTrials.gov; clinical trial registration number: NCT00254293.
评估阿巴西普联合甲氨蝶呤（MTX）治疗类风湿关节炎5年的安全性和有效性。
患者被随机分为接受阿巴西普10或2mg/kg或安慰剂联合MTX治疗。完成1年双盲期的患者进入长期延长期，所有患者均接受固定剂量约10mg/kg的阿巴西普治疗。我们描述了所有接受至少1剂阿巴西普治疗患者的安全性分析以及原约10mg/kg阿巴西普治疗组5年期间的有效性分析。
在235例完成双盲期的接受阿巴西普或安慰剂治疗的患者中，219例进入长期延长期；130例（59.4%）在第5年仍在继续治疗。与双盲期相比，长期延长期未观察到意外的安全事件。不良事件（AE）和严重AE的发生率在第1年分别为489.7和20.0/100患者年，而在累积期分别为374.9和18.9/100患者年。通过探索性分析，10mg/kg组在第1年观察到的改善在第5年得以维持，这通过美国风湿病学会（ACR）反应评估（ACR20：第1年和第5年分别为77.1%对82.7%；ACR50：分别为53.0%对65.4%；ACR70：分别为28.9%对40.4%）以及疾病活动度评估（低疾病活动状态：第1年和第5年分别为48.2%对58.5%；疾病活动评分-28定义的缓解：第1年和第5年分别为25.3%对45.3%）。
阿巴西普在5年治疗期间维持了第1年观察到的疗效，并显示出持续的安全性和耐受性。这些数据以及相对较高的保留率支持了选择性T细胞共刺激调节提供的长期临床益处。
ClinicalTrials.gov；临床试验注册号：NCT00254293。
