Incidence of tuberculosis in patients receiving tumor necrosis factor-α blockers
DOI:
https://doi.org/10.29193/RMU.36.1.2Keywords:
TUBERCULOSIS, LATENT TUBERCULOSIS, ANTI-TNF, TUMOR NECROSIS FACTOR-ALPHA, ADALIMUMAB, ETANERCEPT, INFLIXIMAB, GOLIMUMABEAbstract
Introduction: tuberculosis (TB) is a frequent complication in patients receiving tumor necrosis factor-alpha (TNF-a) blockers. It occurs upon the reactivation of a latent infection or the progression of a recent infection.
Objective: to learn about the incidence of TB in a population receiving tumor necrosis factor-alpha (TNF-a) blockers, to analyze the presentation of this condition and to conduct a latent infection research prior to the initiation of therapy.
Method: retrospective cohort study. Patients receiving tumor necrosis factor-alpha (TNF-a) blockers between 2010 and 2016 were included in the study. Data were obtained from the IT systems of the National Resources Fund and the National Tuberculosis Program. The incidence of TB was calculated and the cases developing TB were described.
Results: 991 treatments were included for 980 patients in total. 9 cases of TB were reported. Global incidence was 419.9 (IC 95% 191.9-591.2) out of 100,000 people per year. Cases of TB were only seen in patients treated with adalimumab. Screening for LTBI upon initiation of the drug was heterogeneous and the disseminated forms of TB prevailed (6/9) over isolated pulmonary affectation (3/9). In all cases anti- TNFa was suspended when TB was diagnosed, and it was not reinitiated.
Conclusions: the incidence of TB in patients receiving tumor necrosis factor-alpha (TNF-a) blockers was 16.5 times greater than in the general population. Disseminated forms of TB prevailed, and some cases occurred in individuals who had received LTBI therapy prior to the initiation of the drug, suggesting the risk persists as long as there is exposure to the drug.
References
(2) Farga V, Caminero JA. Tuberculosis. 3ra ed. Santiago de Chile: Mediterráneo, 2011:474 p.
(3) Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for disease control and prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64:111-5.
(4) Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004; 350:2060-7.
(5) Diel R, Goletti D, Ferrara G, Bothamley G, Cirillo D, Kampmann B, et al. Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Resp J 2011; 37(1): 88-99.
(6) Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Bréban M, et al. 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. Arthritis Rheum 2009; 60:1884-94.
(7) Comisión Honoraria de Lucha Antituberculosa y Enfermedades Prevalentes (CHLA-EP), Facultad de Medicina-UdelaR, Cátedra de Neumología, Cátedra de Enfermedades Infecciosas. Guía nacional para el manejo de la tuberculosis. 3ª ed Montevideo: MSP, 2016:95 p.
(8) Carmona L, Gómez-Reino JJ, Rodríguez-Valverde V, Montero D, Pascual-Gómez E, Mola EM, et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 2005; 52(6):1766-72.
(9) Zhang Z, Fan W, Yang G, Xu Z, Wang J, Cheng Q, et al. Risk of tuberculosis in patients treated with TNF-á antagonists?: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 2017; 7(3):e012567.
(10) Organización Mundial de Salud. Informe mundial sobre la tuberculosis 2015. Sinopsis. OMS, 2015:5p.
(11) World Health Organization. Global tuberculosis report 2018. Geneva: WHO, 2018.
(12) Askling J, Fored CM, Brandt L, Baecklund E, Bertilsson L, Geborek P, et al. Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden. Arthritis Rheum 2005; 52:1986-92.
(13) Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A, et al. 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). Ann Rheumat Dis 2010; 69(3):522-8.
(14) Solovic I, Sester M, Gomez-Reino JJ, Rieder HL, Ehlers S, Milburn HJ, et al. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur Resp J 2010; 36(5):1185-206.
(15) Goletti D, Petrone L, Ippolito G, Niccoli L, Nannini C, Cantini F. Preventive therapy for tuberculosis in rheumatological patients undergoing therapy with biological drugs. Expert Rev Anti Infect Ther 2018; 16(6):501-12.
(16) Pérez Sartori G. Tuberculosis en pacientes inmunodeprimidos no VIH: enfermedad autoinmune, reumatológica e inflamatoria intestinal. En: Comisión Honoraria de Lucha Antituberculosa y Enfermedades Prevalentes (CHLA-EP), Facultad de Medicina-UdelaR. Guía nacional para el manejo de la tuberculosis en situaciones especiales, año 2017. Montevideo: MSP, 2017:79-87.
(17) Mir Viladrich I, Daudén Tello E, Solano-López G, López-Longo FJ, Taxonera Samso C, Sánchez Martínez P, et al. Consensus document on prevention and treatment of tuberculosis in patients for biological treatment. Arch Bronconeumol 2016; 52(1):36-45.
(18) Tomio J, Yamana H, Matsui H, Yamashita H, Yoshiyama T, Yasunaga H. Tuberculosis screening prior to anti-tumor necrosis factor therapy among patients with immune-mediated inflammatory diseases in Japan: a longitudinal study using a large-scale health insurance claims database. Int J Rheum Dis 2017; 2(11):1674-83.
(19) Bartalesi F, Vicidomini S, Goletti D, Fiorelli C, Fiori G, Melchiorre D, et al. QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases. Eur Resp J 2009; 33:586-93.
(20) Lee SH. Diagnosis and treatment of latent tuberculosis infection. Tuberc Resp Dis (Seoul) 2015; 78(2):56-63.
(21) Arias Guillén M. Avances en el diagnóstico de la infección tuberculosa. Arch Bronconeumol 2011; 47(10):521-30.
(22) Freund R, Granger B, Francois C, Carcelain G, Ravaud P, Mariette X, et al. Cost-effectiveness analysis of strategies using new immunological diagnostic tests of latent tuberculosis infection before TNF-blockers therapy. Presse Med 2018; 47:e9-e13.
(23) World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: WHO, 2018:74 p.
(24) Xie X, Li F, Chen JW, Wang J. Risk of tuberculosis infection in anti-TNF-á biological therapy: from bench to bedside. J Microbiol Immunol Infect 2014; 47(4):268-74.
