Monitorization of tuberculosis screening tests during anti-TNF-α treatment in children with rheumatic diseases

Aim: We aimed to investigate the incidence of latent tuberculosis infection (LTBI) and seroconversion rate of LTBI screening testsunder anti-TNF-α treatment, in our pediatric patients with chronic rheumatic diseases.Material and Methods: The data of 47 patients received anti-TNF-α treatment for different chronic rheumatic diseases between May2015 and May-2018, were reviewed retrospectively. Demographics and clinical findings of the patients, as well as the treatments andtheir durations, were collected. The tuberculin skin test (TST) and Quantiferon-TB-Gold in-tube (QFT) test results at initiation andone year after the anti-TNF-α treatment were compared.Results: The study group included 38 (80.8%) patients with juvenile idiopathic arthritis, six (12.7%) with idiopathic uveitis, two (4.2%)with Behçet's disease related uveitis and one (2.1%) with juvenile dermatomyositis. For a period at least one year, 33 (70.2%) patientsreceived etanercept, 12 (25.5%) received infliximab and two (4.2%) received adalimumab treatment. Before anti-TNF-α treatment,31.9% of the patients were diagnosed with LTBI. After one year of treatment, it was found to be increased to 44.6%. During treatment,the seroconversion rate of the screening tests for LTBI was determined to be 12.7% (6/47).Conclusion: The seroconversion rate of screening tests for LTBI was found high in pediatric patients receiving anti-TNF-α treatment.Although the consistency between TST and QFT tests was found weak in our study, the fact that these tests should be used andevaluated together in the follow-up in the light of current guidelines in terms of LTBI and active tuberculosis development, remainsstill up to date. Further research is need in order for more enlightening data on the risk of LTBI and active tuberculosis in patientsunder anti-TNF-α treatment.

PDF

___

1. Wallis RS, Broder MS, Wong JY, et al. Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 2004;38:1261-5.
2. Carmona L, Gómez-Reino JJ, Rodríguez-Valverde V, et al. Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 2005;52:1766-72.
3. World Health Organization. Global tubercolosis report 2019. https://apps.who.int/iris/bitstream/hand le/10665/329368/9789241565714-eng.pdf?ua=1.
4. Centers for Disease Control and Prevention. Burden of TB in the United States. https://www.cdc.gov/featu res/burden-tb-us/index.html.
5. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012;64:625-39.
6. Hatzara C, Hadziyannis E, Kandili A, et al. Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases. Ann Rheum Dis 2015;74:1848- 53.
7. Bermejo F, Algaba A, Chaparro M, et al. How frequently do tuberculosis screening tests convert in inflammatory bowel disease patients on antitumor necrosis factor-α? A pilot study. Dig Liver Dis 2013;45:733-7.
8. Sadovici-Bobeica V, Salaru V, Mazur L, et al. Conversion of tuberculosis screening tests during biological therapy in patients with rheumatic diseases: what's beyond screening values? Eur Respir J 2018;52:5280
9. Lewinsohn DM, Leonard MK, LoBue PA, 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;64:1-33.
10. Tüberküloz Tanı ve Tedavi Rehberi, Ankara: TC Sağlık Bakanlığı, Türkiye Halk Sağlığı Kurumu 2019.
11. Kalfa M, Aksu K. Treatment with tumor necrosis factor-alpha antagonists and infections. RAED J 2011;3:49-56.
12. Dixon WG, Hyrich KL, Watson KD. 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 Rheum Dis 2010;69:522-8.
13. Cuomo G, D’Abrosca V, Iacono D, Pantano I. The conversion rate of tuberculosis screening tests during biological therapies in patients with rheumatoid arthritis. Clin Rheumatol 2017;36:457-61.
14. Nobre CA, Callado MR, Lima JR, et al. Tuberculosis infection in rheumatic patients with infliximab therapy: experience with 157 patients. Rheumatol Int 2012;3:2769-75.
15. Marques CDL, Duarte ALBP, Lorena VMB, et al. Attenuated response to PPD in the diagnosis of latent tuberculosis infection in patients with rheumatoid arthritis. Rev Bras Reumatol 2009;49:121-31.
16. Cerda OL, de Los Angeles Correa M, Granel A, et al. Tuberculin test conversion in patients with chronic inflammatory arthritis receiving biological therapy. Eur J Rheumatol 2019;6:19-22.
17. Ramos S, Nogueira A, Dias A, et al. Tuberculosis screening in patients receiving biological therapy. Acta Reumatol Port 2015;40:234-40.
18. Cohen A, Mathiasen VD, Schön T, et al. The global prevalence of latent tuberculosis: a systematic review and meta-analysis. Eur Respir J 2019;54.
19. Girit S, Ayzıt Atabek A, Senol E, et al. Screening for latent tuberculosis in children with immune-mediated inflammatory diseases treated with anti-tumor necrosis factor therapy: Comparison of tuberculin skin and t-spot tuberculosis tests. Arch Rheumatol 2020;35:1-9.
20. Garcovich S, Ruggeri A, D'Agostino M, et al. Clinical applicability of Quantiferon-TB-Gold testing in psoriasis patients during long-term anti-TNF-alpha treatment: a prospective, observational study. J Eur Acad Dermatol Venereol 2012;26:1572-6.
21. Westhovens R, Yocum D, Han J, Berman A, Strusberg I, Geusens P, et al; START Study Group. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebocontrolled trial. Arthritis Rheum 2006;54:1075-86.
22. Chen DY, Shen GH, Chen YM, et al. Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFα inhibitors: the utility of IFNγ assay. Ann Rheum Dis 2012;71:231-7.