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) - PubMed (original) (raw)

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)

W G Dixon et al. Ann Rheum Dis. 2010 Mar.

Abstract

Background: 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).

Objective: To compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity.

Methods: 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.

Results: 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.

Conclusion: 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.

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Conflict of interest statement

Competing interests: None.

Figures

Figure 1

Figure 1

Models for attributing tuberculosis (TB) to drug treatment. (A) “On drug”. Patient-years and adverse events were attributed to each drug only while the patient was actively receiving that drug. Event A was not attributed to any drug, while event B was attributed to drug 2. (B) “Most recent drug”. Patient-years were accrued for each drug from the start date of that drug until the date of switching to the next anti-tumour necrosis factor drug, irrespective of drug discontinuation. Follow-up was censored at the most recently completed consultant follow-up or death, whichever came first, for all models.

Figure 2

Figure 2

Cumulative incidence of tuberculosis (TB) following first exposure to anti-tumour necrosis factor (anti-TNF) therapy (most recent drug model, with person-years censored at death, last returned follow-up form, or date of switching to second anti-TNF). Numbers in table represent the number of patients eligible for follow-up at the specified follow-up time points. ADA, adalimumab; DMARD, disease-modifying antirheumatic drug; ETA, etanercept; INF, infliximab.

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References

    1. Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999;354:1932–9 - PubMed
    1. Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. [see comment]. N Engl J Med 2001;345:1098–104 - PubMed
    1. Mohan AK, Cote TR, Block JA, et al. Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor. [see comment]. Clin Infect Dis 2004;39:295–9 - PubMed
    1. Wallis RS, Broder MS, Wong JY, et al. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. [see comment]. Clin Infect Dis 2004;38:1261–5 - PubMed
    1. Wallis RS, Broder M, Wong J, et al. Granulomatous infections due to tumor necrosis factor blockade: correction. Clin Infect Dis 2004;39:1254–5 - PubMed

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