Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR)

TLDR

The study aimed to compare tuberculosis risk among rheumatoid arthritis patients treated with the anti‑TNF agents etanercept, infliximab, and adalimumab, including time to event, infection site, and ethnicity effects. Using data from the British Society for Rheumatology Biologics Register, the authors compared TB rates in 10,712 anti‑TNF‑treated patients (3,913 ETA, 3,295 INF, 3,504 ADA) with 3,232 RA patients on conventional disease‑modifying drugs. Tuberculosis occurred three‑ to four‑fold more frequently with infliximab (136/100,000 PY) and adalimumab (144/100,000 PY) than with etanercept (39/100,000 PY), with adjusted incidence rate ratios of 3.1 and 4.2, respectively, a median time to event of 5.5 months for infliximab, 62 % extrapulmonary cases, and a six‑fold higher risk in non‑white patients.

Abstract

The 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).To compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity.Data 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.To 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.The 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.