Impact of Immunosuppressive Therapy on the Performance of Latent Tuberculosis Screening Tests in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Abstract

Screening for latent tuberculosis infection (LTBI) is mandatory before commencing tumor necrosis factor (TNF)-α inhibitor use. However, the impact of immunosuppressive therapy (IST), including corticosteroids and immunomodulators, on the performance of LTBI screening in patients with inflammatory bowel disease (IBD) has not been fully elucidated. We searched all relevant studies published before November 2021 that examined the performance of interferon γ release assays (IGRAs) and tuberculin skin tests (TSTs) in patients with IBD who received IST, using the Medline, EMBASE, and Cochrane Library databases. We performed meta-analyses of positive or indeterminate rates of IGRA or TST according to IST and calculated the concordance rates between IGRA and TST results. A total of 20 studies with 4045 patients were included in the meta-analysis. The IGRA-positive rate was lower in patients on IST than in those not on IST (odds ratio (OR) (95% confidence interval (CI)) = 0.55 (0.39–0.78)), whereas the IGRA-indeterminate rate was higher in patients on IST than in those not on IST (OR (95% CI) = 2.91 (1.36–6.24)). The TST-positive rate did not differ between the on-IST and not-on-IST groups (OR (95% CI) = 0.87 (0.51–1.50)). The concordance rate between IGRA and TST was 83.3% (95% CI, 78.5–88.1%). The IGRA-negative/TST-positive rate tended to be higher than that the IGRA-positive/TST-negative rate (9.5% vs. 5.8%, respectively), although the difference was not statistically significant. In conclusion, IGRA results were negatively affected by IST in patients with IBD, supporting requirements that IGRA should be performed before initiating IST. The use of both an IGRA and TST in patients with IBD on IST may improve the diagnosis rate of LTBI.

Indeterminate results of interferon gamma release assays in the screening of latent tuberculosis infection: a systematic review and meta-analysis

“…Previous meta-analyses have evaluated the indeterminate rate of IGRAs. Two studies assessed the indeterminate rate in HIV-positive patients ( 10 , 11 ), two studies assessed the indeterminate rate in inflammatory bowel disease patients ( 12 , 13 ), and one study assessed the indeterminate rate in patients that underwent an organ transplant ( 14 ). Two large meta-analyses assessed the indeterminate rate in the entire population ( 15 , 16 ); however, active TB, suspected TB, and LTBI were included.…”

Prevalence of indeterminate tuberculosis interferon‐gamma release assays in COVID‐19 patients: Systematic review and meta‐analysis

“…Several immunocompromising conditions, such as HIV infection, 30 advanced liver disease, 31 malnutrition, a low albumin level, 32,33 helminth infection, 34 and corticosteroid use 8,35,36 have been reported to be associated with indeterminate IGRA results.…”

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection

“…The new version, QFT ® -Plus, has shown improvement in the diagnosis of TBI among immunocompromised patients, with better concordance with T-SPOT ® .TB (87.56%) compared to the older version, QFT ® -GIT (83.19%) [ 85 ]. Despite the fact that IGRAs include a positive control tube, both tests have reduced sensitivity in detecting TBI [ 86 , 87 ]; therefore, IGRAs should be performed before initiating immunosuppressive treatment to rule out Mtb infection.…”

“…In mycobacterial infections, IFN-γ released by CD4 + T cells is essential for host survival and enhances both CD4 + and CD8 + T cell activities [ 129 ]. However, false-negative IGRA results were detected in patients with TB infection with advanced age [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , …”