类风湿关节炎患者接受抗肿瘤坏死因子α治疗后的严重感染：从观察性研究数据解读中获得的经验教训
Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies.
作者信息
Dixon W G, Symmons D P M, Lunt M, Watson K D, Hyrich K L, Silman A J
机构信息
University of Manchester, Manchester, UK.
出版信息
Arthritis Rheum. 2007 Sep;56(9):2896-904. doi: 10.1002/art.22808.
OBJECTIVE
In a recent observational study, we found that the risk of serious infection following anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in patients with rheumatoid arthritis (RA) was not importantly increased compared with the background risk in routinely treated RA patients with similar disease severity. Observational data sets are, however, subject to a number of important biases related to selection factors for the timing of starting and stopping therapy. Infection risk is also likely to vary with duration of therapy. This study was undertaken to examine the influences of these biases and of the method of analysis on the risk of infection.
METHODS
We compared the risk of serious infection in 8,659 patients treated with anti-TNFalpha with that in 2,170 patients treated with traditional disease-modifying antirheumatic drugs (DMARDs) recruited to the British Society for Rheumatology Biologics Register. We applied a number of statistical models in which we varied the length of the followup period by using different definitions of the date of discontinuation of treatment and different lag periods of risk following drug cessation.
RESULTS
When the at-risk period was defined as "receiving treatment", the adjusted incidence rate ratio comparing patients receiving anti-TNFalpha therapy with patients receiving DMARD therapy was 1.22 (95% confidence interval [95% CI] 0.88-1.69). Limiting followup to the first 90 days, however, revealed an adjusted incidence rate ratio of 4.6 (95% CI 1.8-11.9). Rates of infection were increased in the 90 days immediately following drug discontinuation and beyond, explained by selection factors for drug discontinuation.
CONCLUSION
These findings show that overall, the way in which UK rheumatologists select patients for starting and discontinuing anti-TNFalpha therapy explains our previous finding of no increase in risk. However, there may be important increases in true risk, notably early in the course of treatment, that would become more evident depending on the definition of at-risk period.
目的
在最近一项观察性研究中，我们发现类风湿关节炎（RA）患者接受抗肿瘤坏死因子α（抗TNFα）治疗后发生严重感染的风险与疾病严重程度相似的常规治疗RA患者的背景风险相比，并未显著增加。然而，观察数据集存在一些与开始和停止治疗时间的选择因素相关的重要偏差。感染风险也可能随治疗持续时间而变化。本研究旨在探讨这些偏差及分析方法对感染风险的影响。
方法
我们将英国风湿病学会生物制剂登记处招募的8659例接受抗TNFα治疗的患者与2170例接受传统改善病情抗风湿药物（DMARDs）治疗的患者的严重感染风险进行了比较。我们应用了多种统计模型，通过使用不同的治疗停药日期定义和停药后不同的风险滞后时间来改变随访期的长度。
结果
当风险期定义为“接受治疗”时，接受抗TNFα治疗的患者与接受DMARD治疗的患者相比，调整后的发病率比为1.22（95%置信区间[95%CI]0.88 - 1.69）。然而，将随访限制在前90天，调整后的发病率比为4.6（95%CI 1.8 - 11.9）。停药后立即及之后的90天内感染率增加，这是由停药的选择因素所解释的。
结论
这些发现表明，总体而言，英国风湿病学家选择患者开始和停止抗TNFα治疗的方式解释了我们之前发现的风险未增加的结果。然而，真实风险可能有重要增加，尤其是在治疗早期，这将根据风险期的定义变得更加明显。
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