Analysis of Infections and All-Cause Mortality in Phase II, Phase III, and Long-Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis
Analysis of Infections and All-Cause Mortality in Phase II, Phase III, and Long-Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis
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DOI：
10.1002/art.38779
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发表时间：
2014-11-01
影响因子：
13.3
通讯作者：
Riese, Richard
中科院分区：
文献类型：
--
作者：
Cohen, Stanley;Radominski, Sebastiao C.;Riese, Richard
目标。目的：通过托法替尼II期、III期和长期延长(LTE)研究，确定中至重度活动期类风湿关节炎(RA)患者的感染率和全因死亡率。对托法替尼在类风湿关节炎患者中的研究数据进行汇总分析。在这些研究中，托法替尼作为单一疗法或与甲氨蝶呤或其他非生物疾病修改的抗风湿药物联合使用。数据纳入截止日期为2012年4月19日。在II期、III期和LTE研究中，4,789名患者接受了tofacitinib(8,460名患者-暴露年)。总的严重感染率为3.09例/100病人年(95%可信区间[95%可信区间]2.73-3.49)，并且随着时间的推移，感染率保持稳定。Cox比例风险模型显示，年龄、皮质类固醇剂量、糖尿病和托法替尼剂量与严重感染的风险独立相关。淋巴细胞计数<0.5×10(3)/mm(3)很少见，但与治疗和/或严重感染的风险增加有关。总体而言，全因死亡率为每100人年0.30次事件(95%可信区间0.20-0.44)。接受tofacitinib治疗的RA患者的总体感染风险(包括严重感染)和死亡率似乎与接受生物制剂治疗的RA患者相似。随着时间的推移，严重感染率保持稳定。
Objective. To determine the rate of infection and all-cause mortality across tofacitinib phase II, phase III, and long-term extension (LTE) studies in patients with moderately to severely active rheumatoid arthritis (RA).Methods. Pooled data from studies of tofacitinib in patients with RA were analyzed. In these studies, tofacitinib was administered as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs. The cutoff date for inclusion of data was April 19, 2012.Results. Across phase II, phase III, and LTE studies, 4,789 patients received tofacitinib (8,460 patient-years of exposure). The overall rate of serious infection was 3.09 events per 100 patient-years (95% confidence interval [95% CI] 2.73-3.49), and rates were stable over time. A Cox proportional hazards model showed that age, corticosteroid dose, diabetes, and tofacitinib dose were independently linked to the risk of serious infection. Lymphocyte counts of < 0.5 x 10(3)/mm(3) were rare but were associated with an increased risk of treated and/or serious infection. Overall, all-cause mortality rates were 0.30 events per 100 patient-years (95% CI 0.20-0.44).Conclusion. The overall risk of infection (including serious infection) and mortality rates in RA patients treated with tofacitinib appear to be similar to those observed in RA patients treated with biologic agents. The rates of serious infection were stable over time.