Background Tuberculosis (TB) is a major concern in patients treated with TNF inhibitors (TNFi), especially in countries with a high TB burden. Careful screening for active and latent TB is mandatory before TNFi initiation, and patients with latent TB receive prophylactic treatment, however this does not influence the risk of TB reinfection/new infection.
Objectives To assess the incidence of active TB and the efficacy of TB prevention measures in a cohort of rheumatoid arthritis (RA) patients receiving TNFi, in a Romanian academic Rheumatology center.
Methods Data of all RA patients who received treatment with TNFi in our clinic between 2001 and 2013 have been retrospectively analyzed. Demographic characteristics, baseline TB screening results, TB prophylaxis, duration of TNFi treatment, and reported active TB were documented. The cohort was divided into 3 groups according to the mandatory TB screening method at baseline: tuberculin skin test (TST) with a positive threshold of either >10mm (01.2001-12.2004) = group TST1, or >5mm (01.2005-08.2010) = group TST2, and QuantiFERON®-TB Gold test (09.2010-12.2013) = group QTF. All patients tested positive for latent TB received prophylaxis with isoniazide for 9 months. The incidence of active TB was analyzed for each group and compared to TB incidence data in Romanian general population, which were retrieved from the World Health Organization (WHO) statistic reports. The influence of the screening method on active TB incidence was assessed using Cox proportional hazard regression.
Results 304 RA patients were included: 50 in TST1, 159 in TST2 and 95 in the QTF group. The number of active TB cases/the time of exposure to TNFi in person-years (PY) in the 3 groups was 6/322.6, 5/708.8 and 1/133.2 respectively, accounting for an incidence of 1860, 705 and 751 cases per 100,000 PY. The incidence of TB in Romania, as reported to the WHO, decreased from 147 to 94 per 100,000 PY from 2001 to 2012.
When analyzing the duration from TNFi initiation to the diagnosis of active TB, only 2/6 cases in TST1 and 1/5 cases in TST2 had less than 6 months (latent TB activation), while all other cases were diagnosed after over 12 months (probably new infection). There was no influence of the TB screening method on the risk of active TB: hazard ratios [95% confidence interval] were 0.34[0.10-1.13] for TST2 and 0.25 [0.03-2.24] for QTF, both p>0.05, when TST1 was the reference group. Similarly, there were no significant differences when comparing groups with regard to latent TB reactivation or to new TB infection. Comparing the QTF group to the combined TST1+TST2 groups led to similar results.
Conclusions In a country with a high TB burden, where all RA patients started on TNFi are screened for latent TB before treatment initiation, new TB infection exceeds latent TB reactivation. TB incidence in these patients is much higher than in the general population and screening at initiation does not solve the problem of later infection.
Disclosure of Interest : None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.