BackgroundThe risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF) therapy, with a proposed differential risk between the anti-TNF drugs etanercept (ETA), infliximab (INF) and adalimumab (ADA).ObjectiveTo compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity.MethodsData from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504 ADA) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs.ResultsTo April 2008, 40 cases of TB were reported, all in the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA (144 events/100 000 person-years) and INF (136/100 000 person-years) than for ETA (39/100 000 person-years). After adjustment, the incidence rate ratio compared with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to 12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated. Patients of non-white ethnicity had a sixfold increased risk of TB compared with white patients treated with anti-TNF therapy.ConclusionThe rate of TB in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving INF and ADA than in those receiving ETA.

Objective. To determine whether the rate of serious infection is higher in anti-tumor necrosis factor (anti-TNF)-treated rheumatoid arthritis (RA) patients compared with RA patients treated with traditional disease-modifying antirheumatic drugs (DMARDs).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. 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.

These data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies. However, the most disabled patients were less likely to respond, despite concurrent MTX. The benefits of NSAIDs may reflect the relative absence of comorbidities in patients who can tolerate these drugs or the continuing presence of reversible inflammatory symptoms. The association of smoking and poor outcome with INF is a novel finding and may reflect alterations in pharmacokinetics. The inability of other baseline disease characteristics to predict the outcome suggests that other factors, including potential genetic differences in drug metabolism, may be influencing the response to anti-TNF-alpha therapies.