Intest Res.  2016 Apr;14(2):146-151. 10.5217/ir.2016.14.2.146.

Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease

• Lee JW
• Choi CH
• Park JH
• Kim JW
• Kang SB
• Koo JS
• Kim YH
• Kim YS
• Joo YE
• Chang SK

• KMID: 2425287
• DOI: http://doi.org/10.5217/ir.2016.14.2.146

Abstract

BACKGROUND/AIMS
Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy.
METHODS
Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB.
RESULTS
The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2-36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients.
CONCLUSIONS
Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.

Keyword

Colitis, ulcerative; Crohn disease; Infliximab; Adalimumab; Tuberculosis

MeSH Terms

Adalimumab
Colitis, Ulcerative
Crohn Disease
Demography
Diagnosis
Humans
Incidence
Infliximab
Inflammatory Bowel Diseases*
Interferons
Lung
Necrosis*
Prevalence
Skin Tests
Tuberculosis*
Interferons

Figure

• 

  Fig. 1 Chest X-ray findings. A representative chest X-ray for the active tuberculosis developed in patients with CD during anti-tumor necrosis factor therapy. A patchy heterogeneous consolidation is visible in the left upper lobe of the lung.

Reference

1. World Health Organization. Global tuberculosis report 2014. Geneva: World Health Organization;2014.

2. Joint Committee for the Revision of Korean Guidelines for Tuberculosis. Korea Centers for Disease Control and Prevention. Korean guidelines for tuberculosis. 2nd ed. Cheongju: Korea Centers for Disease Control and Prevention;2014.

3. Serbina NV, Flynn JL. Early emergence of CD8⁺ T cells primed for production of type 1 cytokines in the lungs of Mycobacterium tuberculosis-infected mice. Infect Immun. 1999; 67:3980–3988. PMID: 10417164.

4. Flynn JL, Chan J. Immunology of tuberculosis. Annu Rev Immunol. 2001; 19:93–129. PMID: 11244032.

5. Thia KT, Loftus EV Jr. , Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol. 2008; 103:3167–3182. PMID: 19086963.

6. Lee KM, Jeen YT, Cho JY, et al. Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis: a Korean multicenter retrospective study. J Gastroenterol Hepatol. 2013; 28:1829–1833. PMID: 23829336.

7. Kim YJ, Kim JW, Lee CK, et al. Clinical outcome of treatment with infliximab in Crohn's disease: a single-center experience. Korean J Gastroenterol. 2013; 61:270–278. PMID: 23756669.

8. Cush JJ. Safety overview of new disease-modifying antirheumatic drugs. Rheum Dis Clin North Am. 2004; 30:237–255. PMID: 15172038.

9. Imperato AK, Bingham CO 3rd, Abramson SB. Overview of benefit/risk of biological agents. Clin Exp Rheumatol. 2004; 22(5 Suppl 35):S108–S114. PMID: 15552523.

10. Solovic I, Sester M, Gomez-Reino JJ, et al. The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur Respir J. 2010; 36:1185–1206. PMID: 20530046.

11. Chung KB, Lee EY, Im JP, Han SK, Yim JJ. Clinical characteristics and treatment responses of patients who developed tuberculosis following use of a tumor necrosis factor-α inhibitor. Korean J Intern Med. 2013; 28:174–179. PMID: 23525649.

12. Seong SS, Choi CB, Woo JH, et al. Incidence of tuberculosis in Korean patients with rheumatoid arthritis (RA): effects of RA itself and of tumor necrosis factor blockers. J Rheumatol. 2007; 34:706–711. PMID: 17309133.

13. Suh YS, Kwok SK, Ju JH, Park KS, Park SH, Yoon CH. Safe readministration of tumor necrosis factor-alpha (TNFalpha) inhibitors in patients with rheumatoid arthritis or ankylosing spondylitis who developed active tuberculosis on previous anti-TNFα therapy. J Korean Med Sci. 2014; 29:38–42. PMID: 24431903.

14. Yoo IK, Choung RS, Hyun JJ, et al. Incidences of serious infections and tuberculosis among patients receiving anti-tumor necrosis factor-alpha therapy. Yonsei Med J. 2014; 55:442–448. PMID: 24532516.

15. Byun JM, Lee CK, Rhee SY, et al. Risks for opportunistic tuberculosis infection in a cohort of 873 patients with inflammatory bowel disease receiving a tumor necrosis factor-alpha inhibitor. Scand J Gastroenterol. 2015; 50:312–320. PMID: 25581784.

16. 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. PMID: 19854715.

17. Tubach F, Salmon D, Ravaud P, 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; 60:1884–1894. PMID: 19565495.

18. Kwon YS, Koh WJ. Diagnosis of pulmonary tuberculosis and nontuberculous mycobacterial lung disease in Korea. Tuberc Respir Dis (Seoul). 2014; 77:1–5. PMID: 25114696.

19. Shim TS. Diagnosis and treatment of latent tuberculosis infection in patients with inflammatory bowel diseases due to initiation of anti-tumor necrosis factor therapy. Intest Res. 2014; 12:12–19. PMID: 25349559.

20. Pai M, Denkinger CM, Kik SV, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev. 2014; 27:3–20. PMID: 24396134.

21. Holden M, Dubin MR, Diamond PH. Frequency of negative intermediate-strength tuberculin sensitivity in patients with active tuberculosis. N Engl J Med. 1971; 285:1506–1509. PMID: 5127141.

22. Diagnostic Standards and Classification of Tuberculosis in Adults and Children. This official statement of the American Thoracic Society and the Centers for Disease Control and Prevention was adopted by the ATS Board of Directors, July 1999. This statement was endorsed by the Council of the Infectious Disease Society of America, September 1999. Am J Respir Crit Care Med. 2000; 161:1376–1395. PMID: 10764337.

23. Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001; 345:1098–1104. PMID: 11596589.

24. Kim ES, Song GA, Cho KB, et al. Significant risk and associated factors of active tuberculosis infection in Korean patients with inflammatory bowel disease using anti-TNF agents. World J Gastroenterol. 2015; 21:3308–3316. PMID: 25805938.

25. Ko WY, Shon HJ, Lee HK, et al. Annual Report on the Notified Tuberculosis in Korea 2014. Korea Centers for Disease Control and Prevention;2015.

26. Abreu C, Magro F, Santos-Antunes J, et al. Tuberculosis in anti-TNF-α treated patients remains a problem in countries with an intermediate incidence: analysis of 25 patients matched with a control population. J Crohns Colitis. 2013; 7:e486–e492. PMID: 23583099.

27. Wolfe F, Michaud K, Anderson J, Urbansky K. Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy. Arthritis Rheum. 2004; 50:372–379. PMID: 14872478.