July 2010

Document Type


Degree Name



Dept. of Public Health and Preventive Medicine


Oregon Health & Science University


Background. Nearly half of the two million people in the U.S. suffering from rheumatoid arthritis (RA) have been treated with anti-TNF drugs that suppress immune functions. Although anti-TNF drug treatment is a highly successful therapy, recent studies indicate that the risk of developing a serious infection is more than 2 times higher among patients taking these drugs. Infections in rheumatoid arthritis patients are often severe and clinically challenging to treat. The objective of this study is to determine if rheumatoid arthritis patients treated with anti-TNF drugs have a higher risk of developing serious skin and soft tissue infections (SSSTIs) that require hospitalization than rheumatoid arthritis patients who do not take anti-TNF drugs. Methods. We conducted a nested case-control study using data from the Veterans Integrated Service Network 20 (VISN 20) undergoing treatment for RA. We used validated electronic algorithms to identify a cohort of actively treated RA patients. Within this cohort cases of serious skin and soft tissue infection were identified and three sets of controls were randomly selected from the same cohort of RA patients and matched by the cases’ index date and VA hospital site number. Multivariate conditional logistic regression was used to test the hypothesis that the risk of serious skin infections among patients taking anti-TNF drugs differs between the two groups, adjusting known confounders and clinically important covariates such as age, sex, ethnicity, other immunosuppressant drug use, co-morbidities, and other autoimmune diseases. Results. Based on conditional logistic regression, anti-TNF use was not significantly associated with SSSTI (OR: 1.4 (95% CI: 0.604-2.30, p = .74) but patients with diabetes (OR 2.4, 95% CI: 4.064, 11.229, p = .001) or a history of skin infection (OR 5.5, 95% CI: 2.713, 11.229, p < .0001) were more likely to have SSSTI. Prednisone use was significant in univariate analysis (OR 1.9, 95% CI: 1.20-3.05, p = .01) but not in the final model (OR 1.5, 95% CI: 0.90-2.52, p = .12). Significance. Serious skin and soft tissue infections are a leading cause of hospitalization and represent a substantial public health burden. Current research into the increase of reported serious infections in RA patients since the introduction of these drugs in the U.S. is limited, establishing a need to evaluate infections that result in hospitalizations. Conclusion. Studies in more generalized RA patient populations have reported a significant increase in infections among patients receiving anti-TNF drugs; however, we did not observe a statistically significant association in the VA patient cohort studied. SSSTIs were not associated with anti-TNF use, but were significantly associated with diabetes, history of skin infection, and high mortality in the VISN 20 RA patient cohort. Further research following these patients prospectively is recommended to provide insight into improving clinical care and preventing future complications and morbidity in this vulnerable patient population.




School of Medicine



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