Abstract
Background
The aims of this study were to determine the incidence of tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease in patients who were treated with tumor necrosis factor (TNF) antagonists in South Korea and to evaluate their clinical characteristics.
Methods
We surveyed all patients (N = 509) who were treated with TNF antagonists at Severance Hospital, South Korea, between January 2002 and December 2011. We reviewed the patients’ medical records and collected microbiological, radiographic, and clinical data, including the type of TNF blocker(s) used and the results of tuberculin skin tests and interferon-gamma release assays.
Results
Rheumatoid arthritis (43.6 %) and ankylosing spondylitis (27.9 %) were the most common diseases in the patients treated with TNF antagonists. Patients received etanercept (33.4 %), infliximab (23.4 %), or adalimumab (13.2 %). The remaining patients received two or more TNF antagonists (30 %). Nine patients developed TB, and four patients developed NTM lung disease. After adjustment for age and sex, the standardized TB incidence ratio was 6.4 [95 % CI 3.1–11.7] compared with the general population. The estimated NTM incidence rate was 230.7 per 100,000 patients per year.
Conclusions
Our results show that mycobacterial infections increase in patients treated with TNF antagonists. The identification of additional predictors of TB for the treatment of latent tuberculosis infection and the careful monitoring and timely diagnosis of NTM-related lung disease are needed for patients who receive long-term therapy with TNF antagonists.
Similar content being viewed by others
References
Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN (2000) Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 343(22):1594–1602
Keat A, Barkham N, Bhalla A, Gaffney K, Marzo-Ortega H, Paul S, Rogers F, Somerville M, Sturrock R, Wordsworth P (2005) BSR guidelines for prescribing TNF-alpha blockers in adults with ankylosing spondylitis. Report of a working party of the British Society for Rheumatology. Rheumatology (Oxford) 44(7):939–947
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353(23):2462–2476
Woolacott NF, Khadjesari ZC, Bruce IN, Riemsma RP (2006) Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic review. Clin Exp Rheumatol 24(5):587–593
Wallis RS (2008) Tumour necrosis factor antagonists: structure, function, and tuberculosis risks. Lancet Infect Dis 8(10):601–611
Solovic I, Sester M, Gomez-Reino JJ, Rieder HL, Ehlers S, Milburn HJ, Kampmann B, Hellmich B, Groves R, Schreiber S, Wallis RS, Sotgiu G, Scholvinck EH, Goletti D, Zellweger JP, Diel R, Carmona L, Bartalesi F, Ravn P, Bossink A, Duarte R, Erkens C, Clark J, Migliori GB, Lange C (2010) The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur Respir J 36(5):1185–1206
Wallis RS, Broder MS, Wong JY, Hanson ME, Beenhouwer DO (2004) Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 38(9):1261–1265
Winthrop KL, Yamashita S, Beekmann SE, Polgreen PM (2008) Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: case finding through the Emerging Infections Network. Clin Infect Dis 46(11):1738–1740
Seong SS, Choi CB, Woo JH, Bae KW, Joung CL, Uhm WS, Kim TH, Jun JB, Yoo DH, Lee JT, Bae SC (2007) Incidence of tuberculosis in Korean patients with rheumatoid arthritis (RA): effects of RA itself and of tumor necrosis factor blockers. J Rheumatol 34(4):706–711
Mankia S, Peters JE, Kang S, Moore S, Ehrenstein MR (2011) Tuberculosis and anti-TNF treatment: experience of a central London hospital. Clin Rheumatol 30(3):399–401
Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A, Symmons DP (2010) 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 69(3):522–528
Taiwo B, Glassroth J (2010) Nontuberculous mycobacterial lung diseases. Infect Dis Clin North Am 24(3):769–789
McGrath EE, Blades Z, McCabe J, Jarry H, Anderson PB (2010) Nontuberculous mycobacteria and the lung: from suspicion to treatment. Lung 188(4):269–282
Arend SM, van Soolingen D, Ottenhoff TH (2009) Diagnosis and treatment of lung infection with nontuberculous mycobacteria. Curr Opin Pulm Med 15(3):201–208
van Ingen J, Boeree MJ, Dekhuijzen PN, van Soolingen D (2008) Mycobacterial disease in patients with rheumatic disease. Nat Clin Pract Rheumatol 4(12):649–656
Kang YA, Lee HW, Yoon HI, Cho B, Han SK, Shim YS, Yim JJ (2005) Discrepancy between the tuberculin skin test and the whole-blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country. JAMA 293(22):2756–2761
Ryoo SW, Shin S, Shim MS, Park YS, Lew WJ, Park SN, Park YK, Kang S (2008) Spread of nontuberculous mycobacteria from 1993 to 2006 in Koreans. J Clin Lab Anal 22(6):415–420
Lee SK, Lee EJ, Kim SK, Chang J, Jeong SH, Kang YA (2012) Changing epidemiology of nontuberculous mycobacterial lung disease in South Korea. Scand J Infect Dis 44(10):733–738
Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ Jr, Winthrop K (2007) An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 175(4):367–416
Gomez-Reino JJ, Carmona L, Valverde VR, Mola EM, Montero MD (2003) Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 48(8):2122–2127
Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, Siegel JN, Braun MM (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345(15):1098–1104
Mootoo A, Stylianou E, Arias MA, Reljic R (2009) TNF-alpha in tuberculosis: a cytokine with a split personality. Inflamm Allergy Drug Targets 8(1):53–62
Lin PL, Plessner HL, Voitenok NN, Flynn JL (2007) Tumor necrosis factor and tuberculosis. J Investig Dermatol Symp Proc 12(1):22–25
Chen DY, Shen GH, Chen YM, Chen HH, Hsieh CW, Lan JL (2012) Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFalpha inhibitors: the utility of IFNgamma assay. Ann Rheum Dis 71(2):231–237
Winthrop KL, Chang E, Yamashita S, Iademarco MF, LoBue PA (2009) Nontuberculous mycobacteria infections and anti-tumor necrosis factor-alpha therapy. Emerg Infect Dis 15(10):1556–1561
Piersimoni C (2012) Nontuberculous mycobacteria infection in solid organ transplant recipients. Eur J Clin Microbiol Infect Dis 31(4):397–403
Iseman MD (2011) Mycobacterial infections in the era of modern biologic agents. Am J Med Sci 341(4):278–280
Bala S, Hastings KL, Kazempour K, Inglis S, Dempsey WL (1998) Inhibition of tumor necrosis factor alpha alters resistance to Mycobacterium avium complex infection in mice. Antimicrob Agents Chemother 42(9):2336–2341
Levin M, Newport MJ, D’Souza S, Kalabalikis P, Brown IN, Lenicker HM, Agius PV, Davies EG, Thrasher A, Klein N et al (1995) Familial disseminated atypical mycobacterial infection in childhood: a human mycobacterial susceptibility gene? Lancet 345(8942):79–83
Acknowledgments
This work was supported by a Grant from the National Research Foundation of Korea funded by the Korean Government (2011-0013018). We thank Jien Kim, Biostatistics Collaboration Unit, Yonsei University College of Medicine, for assistance with the statistical analyses.
Conflict of interest
The authors have no conflict of interest to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, S.K., Kim, S.Y., Kim, E.Y. et al. Mycobacterial Infections in Patients Treated with Tumor Necrosis Factor Antagonists in South Korea. Lung 191, 565–571 (2013). https://doi.org/10.1007/s00408-013-9481-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00408-013-9481-5