抗肿瘤坏死因子α治疗与老年类风湿关节炎患者发生严重细菌感染的风险

Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis.

作者信息

Schneeweiss Sebastian, Setoguchi Soko, Weinblatt Michael E, Katz Jeffrey N, Avorn Jerry, Sax Paul E, Levin Raisa, Solomon Daniel H

机构信息

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02120, USA.

出版信息

Arthritis Rheum. 2007 Jun;56(6):1754-64. doi: 10.1002/art.22600.

DOI:10.1002/art.22600

PMID:17530704

Abstract

OBJECTIVE

To assess the association between the initiation of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy and the risk of serious bacterial infections in routine care.

METHODS

This was a cohort study of patients with rheumatoid arthritis (RA) in whom specific disease-modifying antirheumatic drugs (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical Assistance Contract for the Elderly provided by the state of Pennsylvania. A total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995 and December 31, 2003 were identified using linked data on all prescription drug dispensings, physician services, and hospitalizations. Initiation of anti-TNFalpha therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic agents, and glucocorticoids was compared with initiation of MTX. The main outcome measure was serious bacterial infections that required hospitalization.

RESULTS

The incidence of serious bacterial infections was, on average, 2.2 per 100 patient-years in this population (95% confidence interval [95% CI] 2.0-2.4). Glucocorticoid use doubled the rate of serious bacterial infections as compared with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5-3.1]), with a clear dose-response relationship for dosages >5 mg/day (for < or = 5 mg/day, RR 1.34; for 6-9 mg/day, RR 1.53; for 10-19 mg/day, RR 2.97; and for > or = 20 mg/day, RR 5.48 [P for trend < 0.0001]). Adjusted models showed no increase in the rate of serious infections among initiators of anti-TNFalpha therapy (RR 1.0 [95% CI 0.6-1.7]) or other DMARDs as compared with initiators of MTX.

CONCLUSION

In a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti-TNFalpha therapy compared with users of MTX. Glucocorticoid use was associated with a dose-dependent increase in such infections.

摘要

目的

评估在常规治疗中启动抗肿瘤坏死因子α（抗TNFα）治疗与严重细菌感染风险之间的关联。

方法

这是一项对开始使用特定改善病情抗风湿药物（DMARDs）的类风湿关节炎（RA）患者的队列研究。患者为年龄在65岁及以上（平均年龄76.5岁）的医疗保险受益人，他们同时参加了宾夕法尼亚州提供的老年人药物援助合同。利用所有处方药配药、医生服务和住院的关联数据，确定了1995年1月1日至2003年12月31日期间开始使用DMARD的15597例RA患者。将抗TNFα治疗、除甲氨蝶呤（MTX）外的细胞毒性药物、非细胞毒性药物和糖皮质激素治疗的启动情况与MTX治疗的启动情况进行比较。主要结局指标是需要住院治疗的严重细菌感染。

结果

该人群中严重细菌感染的发生率平均为每100患者年2.2例（95%置信区间[95%CI]2.0 - 2.4）。与使用MTX相比，使用糖皮质激素使严重细菌感染率增加了一倍，与先前是否使用DMARD无关（率比[RR]2.1[95%CI 1.5 - 3.1]），对于剂量>5mg/天有明确的剂量反应关系（对于≤5mg/天，RR 1.34；对于6 - 9mg/天，RR 1.53；对于10 - 19mg/天，RR 2.97；对于≥20mg/天，RR 5.48[趋势P<0.0001]）。校正模型显示，与MTX治疗启动者相比，抗TNFα治疗启动者（RR 1.0[95%CI 0.6 - 1.7]）或其他DMARD治疗启动者的严重感染率没有增加。