Background: The prevalence of tuberculosis (TB) in rheumatoid arthritis (RA) patients is higher than that in the general population, and RA patients are considered a high-risk group. Currently, TB screening of RA patients receiving immunosuppressive therapy such as tumor necrosis factor-α (TNFα) antagonists is performed by the tuberculin skin test (TST) in Japan. Interferon-gamma release assays (QuantiFERON®-TB Gold In-Tube [QFT] and T-SPOT.TB®) are new alternatives to the TST to diagnose latent TB infection (LTBI) and active TB, and offer higher specificity and no cross-reactivity with Bacillus Calmette-Guérin (BCG) vaccine. We evaluated the cost effectiveness of QFT versus TST in non-BCG-vaccinated and BCG-vaccinated RA patients.
Methods: We constructed a Markov model to evaluate the cost effectiveness of QFT and TST. The target population is a hypothetical cohort of 1000 RA patients, using a societal perspective and the lifetime horizon. All costs and clinical benefits were discounted at a fixed annual rate of 3%.
Results: In base-case analysis, the QFT strategy was the most cost effective ($US1044.52; 23.03499 quality-adjusted life-years [QALYs]) compared with the TST strategy for non-BCG-vaccinated RA patients ($US1824.61; 22.98153 QALYs) and for BCG-vaccinated RA patients ($US2096.34; 22.98153 QALYs) [year 2009 values]. The incidence of TB in RA patients with TNFα antagonist therapy influenced the cost effectiveness. When the incidence of TB in RA patients with TNFα antagonist therapy is under 0.00066, the TST strategy is more cost effective than the QFT strategy.
Conclusions: QFT screening is more effective and less costly than the TST for both BCG-vaccinated and non-BCG-vaccinated RA patients prior to TNFα antagonist therapy in Japan. These findings may be applicable to other countries when choosing optimal LTBI screening of RA patients.
Shovman O, Anouk M, Vinnitsky N, et al. QuantiFERON-TB Gold in the identification of latent tuberculosis infection in rheumatoid arthritis: a pilot study. Int J Tuberc Lung Dis 2009 Nov; 13(11): 1427–32PubMedGoogle Scholar
Maeda T, Banno S, Maeda S, et al. Usefulness and limitations of QuantiFERON-TB Gold in Japanese rheumatoid arthritis patients: proposal to decrease the lower cutoff level for assessing latent tuberculosis infection. Mod Rheumatol 2010 Feb; 20(1): 18–23PubMedCrossRefGoogle Scholar
Chen DY, Shen GH, Hsieh TY, et al. Effectiveness of the combination of a whole-blood interferon-gamma assay and the tuberculin skin test in detecting latent tuberculosis infection in rheumatoid arthritis patients receiving adalimumab therapy. Arthritis Rheum 2008 Jun 15; 59(6): 800–6PubMedCrossRefGoogle Scholar
Bocchino M, Matarese A, Bellofiore B, et al. Performance of two commercial blood IFN-gamma release assays for the detection of Mycobacterium tuberculosis infection in patient candidates for anti-TNF-alpha treatment. Eur J Clin Microbiol Infect Dis 2008 Oct; 27(10): 907–13PubMedCrossRefGoogle Scholar
Ponce de Leon D, Acevedo-Vasquez E, Alvizuri S, et al. Comparison of an interferon-gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population. J Rheumatol 2008 May; 35(5): 776–81PubMedGoogle Scholar
Takahashi H, Shigehara K, Yamamoto M, et al. Interferon gamma assay for detecting latent tuberculosis infection in rheumatoid arthritis patients during infliximab administration. Rheumatol Int 2007 Oct; 27(12): 1143–8PubMedCrossRefGoogle Scholar
Takeuchi T, Tatsuki Y, Nogami Y, et al. Postmarketing surveillance of the safety profile of infliximab in 500 Japanese patients with rheumatoid arthritis. Ann Rheum Dis 2008; 67: 189–94PubMedCrossRefGoogle Scholar
Lalvani A, Millington KA. Screening for tuberculosis infection prior to initiation of anti-TNF therapy. Autoimmun Rev 2008 Dec; 8(2): 147–52PubMedCrossRefGoogle Scholar
Oxlade O, Schwartzman K, Menzies D. Interferon-gamma release assays and TB screening in high-income countries: a cost-effectiveness analysis. Int J Tuberc Lung Dis 2007 Jan; 11(1): 16–26PubMedGoogle Scholar
Ministry of Health, Labor and Welfare. Epidemiology of tuberculosis in Japan. Tokyo: Ministry of Health, Labor and Welfare, 2008Google Scholar
Kowada A, Takahashi O, Shimbo T, et al. Cost effectiveness of interferon-gamma release assay for tuberculosis contact screening in Japan. Mol Diagn Ther 2008; 12(4): 235–51PubMedCrossRefGoogle Scholar
de Perio MA, Tsevat J, Roselle GA, et al. Cost-effectiveness of interferon gamma release assays vs tuberculin skin tests in health care workers. Arch Intern Med 2009 Jan 26; 169(2): 179–87CrossRefGoogle Scholar
Hardy AB, Varma R, Collyns T, et al. Cost-effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the QuantiFERON-TB Gold IGRA alone is more cost-effective for immigrants from high burden countries. Thorax 2010 Feb; 65(2): 178–8PubMedCrossRefGoogle Scholar
Mazurek M, Jereb J, Vernon A, et al. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection — United States, 201. MMWR Recomm Rep 2010 Jun 25; 59(RR-5): 1–25PubMedGoogle Scholar
Saag K, Teng G, Patkar N. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rhematoid arthritis. Arthritis Rheum 2008; 59(6): 762–84PubMedCrossRefGoogle Scholar
Kowada A, Deshpande GA, Takahashi O, et al. Cost effectiveness of interferon-gamma release assay versus chest x-ray for tuberculosis screening of BCG-vaccinated elderly populations. Mol Diagn Ther 2010; 14(4): 229–36PubMedCrossRefGoogle Scholar
Diel R, Schaberg T, Loddenkemper R, et al. Enhanced cost-benefit analysis of strategies for LTBI screening and INH chemoprevention in Germany. Respir Med 2009 Dec; 103(12): 1838–53PubMedCrossRefGoogle Scholar
Ministry of Health, Labor and Welfare. Basic survey on wage structure in Japan [in Japanese]. Tokyo: Ministry of Health, Labor and Welfare, 2008Google Scholar
Menzies D, Pai M, Comstock G. Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research. Ann Intern Med 2007; 146(5): 340–54PubMedGoogle Scholar
Diel R, Loddenkemper R, Nienhaus A. Evidence-based comparison of commercial interferon-gamma release assays for detecting active TB: a meta-analysis. Chest 2010; 137(4): 952–68PubMedCrossRefGoogle Scholar
Tuberculosis Research Committee (Ryoken). Relapse rate of tuberculosis treated with standard regimen of chemotherapy [in Japanese]. Kekkaku 2009 Sep; 84(9): 617–25Google Scholar
HorsburghJr CR. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med 2004; 350(20): 2060–7PubMedCrossRefGoogle Scholar
Yoshiyama T. Cost effectiveness analysis of isoniazid preventive therapy to the contacts of tuberculosis patients under Japanese settings. Kekkaku 2010; 75(11): 629–41Google Scholar
Fountain FF, Tolley E, Chrisman CR, et al. Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic. Chest 2005; 128(1): 116–23PubMedCrossRefGoogle Scholar
Diel R, Nienhaus A, Schaberg T. Cost-effectiveness of isoniazid chemo-prevention in close contacts. Eur Respir J 2005; 26(3): 465–73PubMedCrossRefGoogle Scholar
Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008; 149(3): 177–84PubMedGoogle Scholar
Diel R, Loddenkemper R, Nienhaus A. Evidence based comparison of commercial interferon-gamma release assays for detecting active tuberculosis — a meta-analysis. Chest 2010; 137(4): 952–68PubMedCrossRefGoogle Scholar