Methods. This was a national prospective observational study of 7,664 anti-TNF-treated and 1,354 DMARD-treated patients with severe RA from the British Society for Rheumatology Biologics Register. All serious infections, stratified by site and organism, were included in the analysis.

Results. Between December 2001 and September 2005, there were 525 serious infections in the anti-TNF-treated cohort and 56 in the comparison cohort (9,868 and 1,352 person-years of followup, respectively). The incidence rate ratio (IRR), adjusted for baseline risk, for the anti-TNF-treated cohort compared with the comparison cohort was 1.03 (95% confidence interval 0.68-1.57). However, the frequency of serious skin and soft tissue infections was increased in anti-TNF-treated patients, with an adjusted IRR of 4.28 (95% confidence interval 1.06-17.17). There was no difference in infection risk between the 3 main anti-TNF drugs. Nineteen serious bacterial intracellular infections occurred, exclusively in patients in the anti-TNF-treated cohort.

Conclusion. In patients with active RA, anti-TNF therapy was not associated with increased risk of overall serious infection compared with DMARD treatment, after adjustment for baseline risk. In contrast, the rate of serious skin and soft tissue infections was increased, suggesting an important physiologic role of TNF in host defense in the skin and soft tissues beyond that in other tissues.