Negative effect of immunosuppressive therapy in the performance of the QuantiFERON Gold In-Tube test in patients with immune-mediated inflammatory diseases

Abstract

To compare the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFG) for the detection of latent tuberculosis infection among patients with immune-mediated inflammatory diseases before antitumor necrosis factor-α therapy. A prospective study including 153 consecutive patients with rheumatoid arthritis (n = 53), psoriasis (n = 45), inflammatory bowel disease (n = 25), and spondyloarthropathy (n = 22) were included. QFG and TST were performed simultaneously. TST was positive in 43/153 (28.1 %) patients. QFG (cutoff ≥ 0.35 IU/ml) was positive in 15/153 (9.8 %) patients, and indeterminate in one (0.7 %). QFG (cutoff ≥ 0.10 IU/ml) was positive in 25/153 (16.3 %). 59.5 % of the patients were on immunosuppressive therapy at the time of testing. There was a significant difference in the rate of positive QFG between patients with and without immunosuppressive therapy after adjustment for age and gender (cutoff ≥ 0.35 IU/ml, 4.6 vs. 17.4 %; adjusted odds ratio [AOR], 0.2; 95 % confidence interval [CI], 0.06-0.8; p = 0.03 and cutoff ≥ 0.10 IU/ml, 11.2 vs. 24.2 %; AOR, 0.3; 95 % CI, 0.1-0.93; p = 0.04). Agreement between TST and QFG was 'fair' (κ = 0.354 and κ = 0.365, for cutoffs ≥ 0.35 and ≥0.10 IU/ml, respectively). Among patients without immunosuppressive therapy, the concordance between TST and QFG was 'moderate-substantial' (κ = 0.593 and κ = 0.690, for cutoffs ≥ 0.35 IU/ml and ≥0.10 IU/ml, respectively). By contrast, among patients on immunosuppressive therapy the concordance was 'poor' (κ = 0.085; κ = 0.041, respectively). Immunosuppressive therapy affects negatively QFG performance. In patients with immune-mediated inflammatory diseases, QFG may have a limited role for screening of latent tuberculosis infection.

Latent tuberculosis infection in patients with chronic plaque psoriasis who are candidates for biological therapy

“…Immunosuppressive treatments, including biologics, are also known to cause a decrease in the production of IFN-c, which, in turn, could reduce the accuracy of QFT-GIT testing. 34 Our results are consistent with those of Higuchi et al, 35 who showed that 25% of those who were positive for QFT-GIT before isoniazid became negative after treatment. Data regarding the efficacy of isoniazid prophylaxis in patients with psoriasis and LTBI receiving biological therapy are scarce.…”

“…13,33 Causes of variability in serial IGRA testing could be intrinsic to the assay or due to variability in the immune response. 34 Potential causes of intra-assay variability include improper collection, storage, incubation and processing of blood tubes, and variation of the IFN-c measurement. Potential sources for variable immune responses include medications and infections.…”

Prevalence of latent tuberculosis infection in patients with moderate to severe psoriasis taking biologic therapies in a dermatologic private practice in Miami, Florida

“…However, the diagnostic value of IGRA is being questioned in patients with immune-mediated inflammatory diseases, such as psoriasis. 25 In conclusion, the use of a screening tool for LTBI is mandatory in patients taking biologic therapies to avoid severe infectious complications due to the increased risk of TB infections (pulmonary, extrapulmonary, and disseminated) in this population. Periodic follow-up is also crucial as positive results may be seen after prolonged use of these agents.…”

The impact of immunosuppressive therapy on QuantiFERON and tuberculin skin test for screening of latent tuberculosis in patients with inflammatory bowel disease scheduled for anti-TNF therapy

“…However, the optimal strategy in IBD patients has not been yet well-defined as both TST and QFT-G-IT may be negatively affected by disease activity and/or treatment with immunomodulators (IMM), such as azathioprine and methotrexate [6][7][8][9][10][11][12][13][14][15][16][17]. The sensitivity and specificity of TST in the diagnosis of LTB can be limited by high disease activity, malnutrition, treatment with IMM, prior Bacille Calmette-Guerin (BCG) vaccination and/or exposure to environmental mycobacteria [8,9,18,19].…”

“…The sensitivity and specificity of TST in the diagnosis of LTB can be limited by high disease activity, malnutrition, treatment with IMM, prior Bacille Calmette-Guerin (BCG) vaccination and/or exposure to environmental mycobacteria [8,9,18,19]. On the other hand, the sensitivity of QFT-G-IT may be compromised in patients with highly active disease, especially when they have low albumin levels, and in IMM-treated patients with a low lymphocyte count [68, [10][11][12][13]16,20,21]. Nevertheless, a higher accuracy and cost-effectiveness of IGRA compared to the TST has been reported in IBD patients with a prior BCG vaccination and/or on IMM therapy [9,22].…”