Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists

Abstract

Objective. To investigate the impact of official recommendations regarding the management of latent tuberculosis (TB) infection on the rate of active TB in patients receiving treatment with tumor necrosis factor (TNF) antagonists.Methods. Data on active TB rates and on screening and treatment of latent TB infection were extracted from the BIOBADASER (Spanish Society of Rheumatology Database on Biologic Products), a registry of patients with rheumatic conditions treated with TNF antagonists. The rates of active TB among the BIOBADASER patients were compared with those in the background Spanish population, and BIOBADASER patients with rheumatoid arthritis (RA) were compared with a cohort of RA patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) study who were not treated with TNF antagonists and were followed up for 5 years.Results. Active TB developed in 34 patients, of whom 32 started taking TNF antagonists prior to the official recommendations on latent TB infection (pre-OR) and 2 began treatment after the recommendations were issued (post-OR). All cases of TB occurred during treatment with infliximab, and 28 of these patients had RA. Pre-OR, the active TB rate in BIOBADASER patients was 20.9-fold higher than in the background Spanish population, while RA patients in the BIOBADASER had rates 22.6-and 6.2-fold higher than the background and EMECAR populations, respectively. Post-OR, 324 patients with a tuberculin skin test result >5 mm and/or chest radiograph findings suggestive of past TB were treated for 9 months with isoniazid (INH). Post-OR, active TB rates among the BIOBADASER patients decreased by 78% (incidence risk ratio [IRR] 0.22, 95% confidence interval [95% CI] 0.03-0.88; P ‫؍‬ 0.008), while among RA patients in the BIOBADASER, the rate dropped by 83% and reached the EMECAR rate (IRR 1.0, 95% CI 0.02-8.2). There were no INH treatmentrelated hospitalizations or deaths.Conclusion. Strategies to treat latent TB infection that are tailored to the at-risk population can effectively and safely lessen the likelihood of active TB in patients treated with TNF antagonists.

Risk of tuberculosis is higher with anti–tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three‐year prospective french research axed on tolerance of biotherapies registry

“…Our study also confirmed that, as emphasized by other investigators (8), anti-TB chemoprophylactic treatment is efficient for preventing TB. None of our patients with TB had received a correct prophylactic antibiotic against TB.…”

“…Most cases of TB develop soon after treatment initiation and correspond to reactivation of a latent TB infection (4,5). Scientific organizations and health authorities worldwide have proposed recommendations for screening patients with latent TB infection and treating such patients before initiating anti-TNF treatment, and the effectiveness of these recommendations has been demonstrated (8).…”

Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection

“…Implementation failures commonly relate to factors extrinsic to the guidelines; however, intrinsic factors contribute as well (9 -11). In a previous study, we estimated that in roughly 20% of patients in BIOBA-DASER, the physician failed to follow recommendations to manage LTBI, and we wondered about the future impact of this setback on the rate of new ATB (2). A straightforward explanation was not identified, although we believed that the increasing surplus of work represented for these new therapies was at play.…”

“…The recommendations include 9 months of isoniazid (INH) treatment for patients falling into one of the following categories: 1) a tuberculin skin test (TST) result Ն5 mm or a 2-step TST result Ն5 mm (if the first result was Ͻ5 mm); 2) a chest radiograph showing evidence of past tuberculosis; and 3) exposure to ATB or prior partially treated ATB. The significant impact of these recommendations was published elsewhere (2). Following this salient impact, new ATB cases were reported at a much lower rate.…”

Anti–tumor necrosis factor α therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis

“…Calendar time was modeled by including multiple indicator terms to adjust for possible changes in DMARD choice during the study period and possible changes in the prevention of serious infections in this population (24). Statistical analysis.…”