A placebo-controlled, randomized, double-blinded study evaluating the safety of etanercept in patients with rheumatoid arthritis and concomitant comorbid diseases
A placebo-controlled, randomized, double-blinded study evaluating the safety of etanercept in patients with rheumatoid arthritis and concomitant comorbid diseases
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DOI：
10.1093/rheumatology/kem033
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发表时间：
2007-07-01
期刊：
影响因子：
5.5
通讯作者：
Baumgartner, Scott W.
中科院分区：
文献类型：
--
作者：
Weisman, Michael H.;Paulus, Harold E.;Baumgartner, Scott W.
目标。评价依那西普治疗类风湿关节炎（RA）及其合并症的安全性。在一项为期16周的安慰剂对照、随机、双盲研究中，对伴有至少一种合并症（即糖尿病、慢性肺病、近期肺炎、复发性感染）的RA患者使用依那西普（25mg，每周两次）的安全性进行了评估。主要终点是医学上重要感染（Mils，定义为导致住院或静脉注射抗生素治疗的感染）的发生率。分析了535名患者的数据；由于入组缓慢和感染发生率低于预期，该研究被提前终止。严重不良事件（安慰剂组5.9%，依那西普组8.6%）最常见于心血管系统。6例患者（1例安慰剂，5例依那西普）在研究期间死亡；4例死亡归因于心血管事件。依那西普组较高的死亡率没有统计学意义[相对危险度(95% CI) = 5.06(0.59, 42.99)]，但仍无法解释。在总研究人群或bb0 = 65岁、患有糖尿病或患有慢性肺部疾病的患者亚组中，未观察到依坦接受相关的mls发生率（安慰剂组为3.7%，依坦接受组为3.0%）或总体感染的增加。伴有合并症的RA患者对依那西普的耐受性一般良好。依那西普组发生严重不良事件和死亡的频率更高，但事件数量少，Cis范围广，因此无法得出可靠的结论。尽管该研究的统计效力有限，但依那西普治疗并未增加这些患者的mls发生率。
Objective. To evaluate the safety of etanercept in patients with rheumatoid arthritis (RA) and concomitant comorbidities.Methods. The safety of etanercept (25mg twice weekly) in RA patients with at least one comorbidity (i.e. diabetes mellitus, chronic pulmonary disease, recent pneumonia, recurrent infections) was evaluated in a 16-week placebo-controlled, randomized, double-blinded study. The primary endpoint was the incidence of medically important infections (Mils; defined as those resulting in hospitalization or treatment with intravenous antibiotics).Results. Data from 535 patients were analysed; the study was terminated early because of slow enrolment and lower than predicted incidence of infections. Serious adverse events (5.9% placebo, 8.6% etanercept) were most commonly observed in the cardiovascular system. Six patients (1 placebo; 5 etanercept) died during the study; four deaths were attributed to cardiovascular events. The numerically higher mortality in the etanercept group was not statistically significant [relative risk (95% CI) = 5.06 (0.59, 42.99)] but remains unexplained. No etane rcept- related increase in the incidence of Mlls (3.7% placebo, 3.0% etanercept) or overall infections was observed in the total study population or in subgroups of patients who were >= 65 yrs of age, had diabetes or had chronic pulmonary disease.Conclusions. Etanercept was generally well tolerated by RA patients with comorbidities. Serious adverse events and deaths occurred more frequently in the etanercept group but event numbers were small and Cis were broad, preventing reliable conclusions from being drawn. Although the study had limited statistical power, the incidence of Mlls in these patients was not increased by etanercept treatment.