Lacaille Diane, Guh Daphne P, Abrahamowicz Michal, Anis Aslam H, Esdaile John M
University of British Columbia and Arthritis Research Centre of Canada, 895 West 10th Avenue, Vancouver, BC, Canada.
Arthritis Rheum. 2008 Aug 15;59(8):1074-81. doi: 10.1002/art.23913.
Rheumatoid arthritis (RA) is associated with increased frequency of and mortality from infections, which may be related to host factors, RA itself, inflammation, or medication side effects. This study was undertaken to determine the effect of nonbiologic disease-modifying antirheumatic drugs (DMARDs) on infection risk in RA.
We performed a retrospective, longitudinal study of a population-based RA cohort in British Columbia, Canada, followed from January 1996 to March 2003 using administrative data. We evaluated mild infections (requiring a physician visit or antibiotics) and serious infections (requiring or complicating hospitalization). Adjusted risk of mild and serious infections associated with DMARD exposure was estimated using generalized estimating equation extension of multivariate Poisson regression models, after adjusting for baseline covariates (age, sex, RA duration, socioeconomic status) and time-dependent covariates (corticosteroids, comorbidity, prior infections).
A total of 27,710 individuals with RA provided 162,710 person-years of followup. Of these, 25,608 (92%) had at least 1 mild infection and 4,941 (18%) had at least 1 serious infection. Use of DMARDs without corticosteroids was associated with a small decrease in mild infection risk of statistical significance but unclear clinical significance (adjusted rate ratio [RR] 0.90, 95% confidence interval [95% CI] 0.88-0.93 relative to no corticosteroid or DMARD use). Use of DMARDs without corticosteroids was not associated with increased serious infection risk (adjusted RR 0.92, 95% CI 0.85-1.0). Use of corticosteroids increased the risk of mild and serious infections.
Our results indicate that use of nonbiologic DMARDs, including methotrexate, does not increase the risk of infection in RA, whereas use of corticosteroids does. This has important implications for counseling individuals with RA concerning risks and benefits of DMARDs.
类风湿关节炎（RA）与感染的发生率增加及死亡率升高相关，这可能与宿主因素、RA本身、炎症或药物副作用有关。本研究旨在确定非生物性改善病情抗风湿药（DMARDs）对RA患者感染风险的影响。
我们对加拿大不列颠哥伦比亚省一个基于人群的RA队列进行了一项回顾性纵向研究，利用行政数据从1996年1月至2003年3月进行随访。我们评估了轻度感染（需要就医或使用抗生素）和严重感染（需要住院或导致住院复杂化）。在调整基线协变量（年龄、性别、RA病程、社会经济状况）和时间依赖性协变量（皮质类固醇、合并症、既往感染）后，使用多变量泊松回归模型的广义估计方程扩展来估计与DMARD暴露相关的轻度和严重感染的调整风险。
共有27,710例RA患者提供了162,710人年的随访。其中，25,608例（92%）至少发生1次轻度感染，4,941例（18%）至少发生1次严重感染。不使用皮质类固醇的DMARDs使用与轻度感染风险有统计学意义的小幅降低相关，但临床意义不明确（相对于不使用皮质类固醇或DMARDs，调整后的率比[RR]为0.90，95%置信区间[95%CI]为0.88 - 0.93）。不使用皮质类固醇的DMARDs使用与严重感染风险增加无关（调整后的RR为0.92，95%CI为0.85 - 1.0）。使用皮质类固醇会增加轻度和严重感染的风险。
我们的结果表明，包括甲氨蝶呤在内的非生物性DMARDs的使用不会增加RA患者的感染风险，而皮质类固醇的使用会增加感染风险。这对于向RA患者咨询DMARDs的风险和益处具有重要意义。
