Burmester Gerd R, Matucci-Cerinic Marco, Mariette Xavier, Navarro-Blasco Francisco, Kary Sonja, Unnebrink Kristina, Kupper Hartmut
Arthritis Res Ther. 2014 Jan 27;16(1):R24. doi: 10.1186/ar4452.
Patients with active rheumatoid arthritis who had failed at least one disease-modifying anti-rheumatic drug (DMARD) were treated with adalimumab (ADA) in the ReAct study with the option to continue treatment for 5 years in ReAlise. The purpose of this study was to evaluate the long-term safety and effectiveness of ADA as prescribed from the first injection in ReAct to the last observation in ReAlise.
Patients received ADA alone or in combination with DMARDs according to usual clinical care practices. Adverse events (AEs) were tabulated by five time windows after the first ADA injection. Effectiveness measures included achievement of low disease activity (LDA), defined as Simplified Disease Activity Index (SDAI) ≤11, or remission, (REM), defined as SDAI ≤3.3.
Of the 6,610 ReAct patients, 3,435 (52%) continued in ReAlise. At baseline in ReAct, mean age was 54 years, mean DAS28 was 6.0 and mean HAQ DI was 1.64. The mean treatment duration was 1,016 days, representing 18,272 patient-years (PYs) of ADA exposure. Overall incidence rates of serious AEs and serious infections were 13.8 and 2.8 events (E)/100 PYs, respectively. Serious AEs occurred most frequently in the first 6 months and deceased thereafter. Standardised mortality ratio was 0.71 (95% CI 0.57 to 0.87) and standardised incidence ratio for malignancies was 0.64 (95% CI 0.53 to 0.76). LDA was achieved by 50% and REM by 21% of patients at last observation.
Results of this large observational study of ADA in routine clinical practice were consistent with controlled trials, with no new safety concerns during a follow-up of more than 5 years. Effectiveness of ADA was maintained during long-term observation.
NCT00448383, NCT00234884.
在ReAct研究中，至少一种改善病情抗风湿药物（DMARD）治疗失败的活动性类风湿关节炎患者接受了阿达木单抗（ADA）治疗，并可选择在ReAlise研究中继续治疗5年。本研究的目的是评估从ReAct首次注射至ReAlise最后一次观察期间按处方使用ADA的长期安全性和有效性。
患者根据常规临床护理实践单独接受ADA或与DMARD联合使用。在首次注射ADA后的五个时间窗内列出不良事件（AE）。有效性指标包括达到低疾病活动度（LDA），定义为简化疾病活动指数（SDAI）≤11，或缓解（REM），定义为SDAI≤3.3。
6610例ReAct患者中，3435例（52%）继续参与ReAlise研究。在ReAct研究基线时，平均年龄为54岁，平均DAS28为6.0，平均HAQ DI为1.64。平均治疗持续时间为1016天，相当于18272患者年（PYs）的ADA暴露时间。严重AE和严重感染的总发生率分别为13.8和2.8事件（E）/100 PYs。严重AE最常发生在最初6个月，此后减少。标准化死亡率为0.71（95%CI 0.57至0.87），恶性肿瘤标准化发病率为0.64（95%CI 0.53至0.76）。在最后一次观察时，50%的患者达到LDA，21%的患者达到REM。
这项在常规临床实践中对ADA进行的大型观察性研究结果与对照试验一致，在超过5年的随访期间没有新的安全问题。在长期观察中维持了ADA的有效性。
NCT00448383，NCT00234884。
