Simard Julia F, Mittleman Murray A, Shadick Nancy A, Karlson Elizabeth W
Department of Epidemiology, Harvard School of Public Health, Boston, USA ; Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.
Department of Epidemiology, Harvard School of Public Health, Boston, USA.
Open J Rheumatol Autoimmune Dis. 2012 May;2(2):14-20. doi: 10.4236/ojra.2012.22004.
Anti-TNF treatment may increase infection risk, although this has been difficult to study because the timing of anti-TNF treatment is driven by disease activity, which may influence infection susceptibility leading to confounding that varies over time. We evaluated the association between anti-TNF initiation in rheumatoid arthritis (RA) patients on disease modifying anti-rheumatic drugs (DMARD) and infection using multiple approaches adjusting for time-varying confounding.
383 anti-TNF-naïve RA patients on ≥1 non-biologic-DMARD at enrollment from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) were followed up to two years. Pooled logistic regressions estimated the association between anti-TNF and infection by including time-varying covariates in the adjusted models and inverse probability treatment weighting (IPTW).
Adjustment for time-varying disease activity and other suspected confounders yielded non-statistically significant positive associations between anti-TNF start and infection regardless of analytic approach (RR = 2.1, 95% CI: 0.8 - 5.8).
Incorporating changing clinical status, and treatment indications and consequences, yielded consistently (though not significantly) elevated relative risks of infection associated with anti-TNF initiation. Due to limited statistical power, we cannot draw firm conclusions. However, we have illustrated multiple approaches adjusting for potential time-varying confounding in longitudinal studies and hope to replicate the approaches in larger studies.
抗TNF治疗可能会增加感染风险，尽管由于抗TNF治疗的时机由疾病活动度决定，这使得研究变得困难，疾病活动度可能会影响感染易感性，从而导致随时间变化的混杂因素。我们使用多种方法对随时间变化的混杂因素进行调整，评估了类风湿关节炎（RA）患者在使用改善病情抗风湿药物（DMARD）的基础上开始使用抗TNF治疗与感染之间的关联。
来自布莱根妇女医院类风湿关节炎序贯研究（BRASS）的383例初治抗TNF的RA患者，在入组时使用≥1种非生物DMARD，随访两年。通过在调整模型中纳入随时间变化的协变量和逆概率处理加权（IPTW），汇总逻辑回归估计抗TNF与感染之间的关联。
无论采用何种分析方法，对随时间变化的疾病活动度和其他可疑混杂因素进行调整后，抗TNF开始使用与感染之间的正相关均无统计学意义（RR = 2.1，95% CI：0.8 - 5.8）。
纳入不断变化的临床状态、治疗指征和后果后，与抗TNF开始使用相关的感染相对风险持续（尽管不显著）升高。由于统计效力有限，我们无法得出确凿结论。然而，我们展示了在纵向研究中对潜在的随时间变化的混杂因素进行调整的多种方法，并希望在更大规模的研究中重复这些方法。
