Tuberculosis and TNF-α inhibitors in children: how to manage a fine balance
Keywords:
Tuberculosis, latent tuberculosis, TNF inhibitors, children, immune.mediated diseasesAbstract
Since the introduction of biologic response modifiers (BRMs) in the management of children affected by the immune-mediated inflammatory disease, these patients substantially improved their quality of life. BRMs are generally well tolerated and effective in most children and adolescents refractory to conventional immunosuppressive therapy. On the other hand, patients receiving BRMs, especially TNF-α inhibitors, display an increased risk of primary infections or reactivations, i.e. due to Mycobacterium tuberculosis. M. tuberculosis can cause severe disease with consequent short- and long-term morbidity in children on anti-TNF-α treatment. The present paper analyses the increased risk of reactivation of latent tuberculosis infection (LTBI) or de novo TB infection in children treated with TNF-α inhibitors, with the purpose to provide recommendations for screening strategies and safety monitoring of paediatric patients. Special attention is also given to the currently available TB screening tools (IGRAs and TST) and their utility in the diagnosis of LTBI before starting the biologic therapy and during the treatment. Finally, the paper analyses the suggested TB-preventing therapies to adopt in these children and the correct timing to overlap anti-TB and anti-TNF-a treatment.
References
Lamireau T, Cézard JP, Dabadie A, et al. Efficacy and tolerance of infliximab in children and adolescents with Crohn's disease. Inflamm Bowel Dis 2004;10:745–750.
Woo MH, Cho YH, Sohn MJ, et al. Use of Anti-TNF Alpha Blockers Can Reduce Operation Rate and Lead to Growth Gain in Pediatric Crohn's Disease. Pediatr Gastroenterol Hepatol Nutr 2019;22:358–368.
Toussi SS, Pan N, Walters HM, et al. Infections in children and adolescents with juvenile idiopathic arthritis and inflammatory bowel disease treated with tumor necrosis factor-α inhibitors: systematic review of the literature. Clin Infect Dis 2013;57:1318–1330.
Zhang Z, Fan W, Yang G, et al. risk of tuberculosis in patients treated with TNF-α antagonists: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2017;7:e012567.
Baddley JW, Cantini F, Goletti D, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules (I): anti-tumor necrosis factor-α agents). Clin Microbiol Infect 2018;24 Suppl 2:S10–S20.
Singh JA, Wells GA, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev 2011;(2):CD008794.
Ai JW, Ruan QL, Liu QH, Zhang WH. Updates on the risk factors for latent tuberculosis reactivation and their managements. Emerg Microbes Infect. 2016;5:e10.
Askling J, Fored CM, Brandt L, et al. Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden. Arthritis Rheum 2005;52:1986–1992.
Davies HD; Committee On Infectious Diseases. Infectious Complications With the Use of Biologic Response Modifiers in Infants and Children. Pediatrics 2016;138:e20161209.
Abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis. NICE Guidelines, 2015. www.nice.org.uk.
Silva DAAD, Silva MVD, Barros CCO, et al. TNF-α blockade impairs in vitro tuberculous granuloma formation and down modulate Th1, Th17 and Treg cytokines. PLoS One 2018;13(3):e0194430.
Dorhoi A, Kaufmann SH. Tumor necrosis factor alpha in mycobacterial infection. Semin Immunol 2014;26:203–209.
Fallahi-Sichani M, Schaller MA, Kirschner DE, et al. Identification of key processes that control tumor necrosis factor availability in a tuberculosis granuloma. PLoS Comput Biol 2010;6(5):e1000778.
Cao BL, Qasem A, Sharp RC, et al. Systematic review and meta-analysis on the association of tuberculosis in Crohn's disease patients treated with tumor necrosis factor-α inhibitors (Anti-TNFα). World J Gastroenterol 2018;24:2764–2775.
Dheda K, Chang JS, Lala S, et al. Gene expression of IL17 and IL23 in the lungs of patients with active tuberculosis. Thorax 2008;63:566–568.
de Jager W, Hoppenreijs EP, Wulffraat NM, et al. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann Rheum Dis 2007;66:589–98.
van den Ham HJ, de Jager W, Bijlsma JW, et al. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis. Rheumatology 2009;48:899–905
World Health Organization. Global tuberculosis report, 2017. www.who.int › tb › global_report › gtbr2017_main_text.
Ayaz NA, Demirkaya E, Bilginer Y, et al. Preventing tuberculosis in children receiving anti-TNF treatment. Clin Rheumatol 2010;29:389–392.
Kurt OK, Kurt B, Talay F, et al. Intermediate to long-term follow-up results of INH chemoprophylaxis prior to anti-TNF-alpha therapy in a high-risk area for tuberculosis. Wien Klin Wochenschr 2013;125:616–620.
Dantes E, Tofolean DE, Fildan AP, et al. Lethal disseminated tuberculosis in patients under biological treatment - two clinical cases and a short review. J Int Med Res 2018;46:2961–2969.
Noguera-Julian A, Calzada-HernÁndez J, Brinkmann F, et al. Tuberculosis disease in children and adolescents on therapy with anti-tumor necrosis factor-alpha agents: a collaborative, multi-centre ptbnet study. Clin Infect Dis 2019;ciz1138.
Tarkiainen M, Tynjala P, Vahasalo P, Lahdenne P. Occurrence of adverse events in patients with JIA receiving biologic agents: long-term follow-up in a real-life setting. Rheumatology (Oxford) 2015; 54:1170-6
Becker I, Horneff G. Risk of serious infection in juvenile idiopathic arthritis patients associated with tumor necrosis factor inhibitors and disease activity in the German Biologics in Pediatric Rheumatology Registry. Arthritis Care Res 2017; 69:552-60.
Swart J, Giancane G, Horneff G, et al. Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries. Arthritis Res Ther 2018; 20:285.
Nagy A, Mátrai P, Hegyi P, et al. The effects of TNF-alpha inhibitor therapy on the incidence of infection in JIA children: a meta-analysis. Pediatr Rheumatol Online J 2019;17:4.
Dixon WG, Hyrich KL, Watson KD, 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 Rheum Dis 2010; 69: 522–528.
Venturini E, Tersigni C, Chiappini E, et al. Optimising the management of children with latent tuberculosis infection. Expert Rev Anti Infect Ther 2017;15:341–349.
Cruz AT, Hersh AL, Starke JR, et al. Controversies in tuberculous infection among pediatric infectious disease specialists in North America. Int J Tuberc Lung Dis 2016;20:1463–1468.
Garazzino S, Galli L, Chiappini E, et al. performance of interferon-γ release assay for the diagnosis of active or latent tuberculosis in children in the first 2 years of age: a multicenter study of the Italian Society of Pediatric Infectious Diseases. Pediatr Infect Dis J 2014;33:e226–e231.
Hradsky O, Ohem J, Zarubova K, et al. Disease activity is an important factor for indeterminate interferon-γ release assay results in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2014;58:320–324.
González-Moreno J, García-Gasalla M, Losada-López I, et al. IGRA testing in patients with immune-mediated inflammatory diseases: which factors influence the results? Rheumatol Int 2018;38:267–273.
Tebruegge M, Clifford V, Curtis N. Interferongamma release assays should not replace tuberculin skin tests in screening programs for children. Pediatr Infect Dis J 2016;35:929.
NICE guideline. Tuberculosis. 2016. https://www.nice.org.uk/guidance/ng33
Marino A, Chiappini E, Cimaz R, Simonini G. Prebiologic therapy tuberculosis screening experience in a pediatric rheumatology center: TST and IGRA are both necessary. Pediatr Infect Dis J 2017;36:440–441.
Shim TS. Diagnosis and Treatment of Latent Tuberculosis Infection due to Initiation of Anti-TNF Therapy. Tuberc Respir Dis (Seoul) 2014;76:261–268.
Ringold S, Weiss PF, Beukelman T, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum 2013;65:2499–2512.
Edwards A, Gao Y, Allan RN, et al. Corticosteroids and infliximab impair the performance of interferon-gamma release assays used for diagnosis of latent tuberculosis. Thorax 2017; 72:946-9.
Getahun H, Matteelli A, Chaisson RE, Raviglione M. Latent Mycobacterium tuberculosis infection. N Engl J Med 2015;372:2127–2135.
Duarte R, Campainha S, Cotter J, et al. Position paper on tuberculosis screening in patients with immune mediated inflammatory diseases candidates for biological therapy. Acta Reumatol Port 2012;37:253–259.
Cantini F, Nannini C, Niccoli L, et al. Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice. Autoimmun Rev 2015;14:503–509.
Hasan T, Au E, Chen S, et al. Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines. BMJ Open 2018;8:e022445.
Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. Am J Transplant 2020;20:1196–1206.
British Thoracic Society Standards of Care Committee. BTS recommendations for assessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment. Thorax 2005;60:800–805.
Getahun H, Matteelli A, Abubakar I, et al. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J 2015;46:1563–1576.
Diallo T, Adjobimey M, Ruslami R, et al. Safety and Side Effects of Rifampin versus Isoniazid in Children. N Engl J Med 2018;379:454–463.
Cruz AT, Starke JR. Safety and adherence for 12 weekly doses of isoniazid and rifapentine for pediatric tuberculosis infection. Pediatr Infect Dis J 2016;35:811–813.
Rasul CH, Das SC. Vitamin B6 supplementation with isoniazid therapy. Trop Doct 2000;30:55–56.
Dooley KE, Hanna D, Mave V, et al. Advancing the development of new tuberculosis treatment regimens: The essential role of translational and clinical pharmacology and microbiology. PLoS Med 2019;16:e1002842.
Gabriele F, Trachana M, Simitsopoulou M, et al. Performance of QuantiFERON®-TB Gold In-Tube assay in children receiving disease modifying anti-rheumatic drugs. World J Pediatr 2017;13:472–478.
Vortia E, Uko VE, Yen-Lieberman B, et al. Low indeterminate rates associated with use of the quantiferon-tb gold in-tube test in children with inflammatory bowel disease on long-term infliximab. Inflamm Bowel Dis 2018;24:877–882.
Matsumoto T, Tanaka T. Continuation of Anti-TNF therapy for Reumatoid arthritis in patients with active tuberculosis reactivated during anti-TNF medication is more beneficial than its cessation. J Infect Dis Ther 2015; 3:35-37.
Winthrop KL, Mariette X, Silva JT, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules (II): agents targeting interleukins, immunoglobulins and complement factors). Clin Microbiol Infect 2018;24 Suppl 2:S21–S40.
Downloads
Published
Issue
Section
License
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
How to Cite
