Corticosteroids and infliximab impair the performance of interferon-γ release assays used for diagnosis of latent tuberculosis

Edwards, Alexander J.; Gao, Yifang; Allan, Raymond N.; Ball, Darran; Coelho, Tracy; Clifford, Vanessa; Curtis, Nigel; Williams, Anthony P.; Faust, Saul N; Mansour, Salah; Marshall, Ben G.; Elkington, Paul; Tebruegge, Marc

doi:10.1136/thoraxjnl-2016-209397

Cited by 42 publications

(32 citation statements)

References 22 publications

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“…As per this study, IGRA does not appear to be affected by corticosteroid or immunosuppressant therapy . However, this may not always be the case as shown in an ex vivo study in which corticosteroids and infliximab reduced the performance of IGRA . At present, IGRA is possibly more reliable than the other options available.…”

Section: Aims and Methodsmentioning

confidence: 50%

“…An association between anti‐TNF therapy and development of TB was noted when the FDA MedWatch spontaneous reporting system demonstrated 70 TB cases in a median of 12 weeks after initial infliximab exposure, in 2001 . Both extrapulmonary and disseminated TB are more common in patients treated with anti‐TNF therapy, compared with immunocompetent patients .…”

Section: Aims and Methodsmentioning

confidence: 99%

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Review article: managing the adverse events caused by anti‐TNF therapy in inflammatory bowel disease

Shivaji

Sharratt

Thomas

et al. 2019

Aliment Pharmacol Ther

107

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Background: Biological therapy is currently widely used to treat IBD. Infliximab, adalimumab and golimumab are currently licensed anti-TNF therapies. Biosimilar anti-TNF monoclonal antibodies are increasingly used. Anti-TNF therapies are widely used and their adverse effects are well characterised, and may cause significant morbidity and mortality in a small proportion of exposed patients. Gastroenterologists need to understand the mechanisms for these effects, recognise these swiftly and manage such events appropriately. Aim:To cover the range of potential adverse reactions as a result of biologic therapy and specifically management of these events. Methods: A Medline and Pubmed search was undertaken. Search terms includedwere "anti-TNF," "infliximab" or "adalimumab" or "golimumab" combined with the keywords "ulcerative colitis" or "Crohn's disease" or "inflammatory bowel disease" and then narrowed to articles containing the keywords "complications," "side effects" or "adverse events" or "safety profile." International guidelines were also reviewed where relevant.Results: Adverse events discussed in this review include infusion reactions, blood disorders and infections (including bacterial, viral, fungal and opportunistic infections) as well as autoimmune, dermatological disorders, cardiac and neurological conditions. Malignancies including solid organ, haematological and those linked to viral disease are discussed. Conclusions:Anti-TNF therapy has wide-ranging effects on the immune system resulting in a spectrum of potential adverse events in a small proportion of patients.Research advances are improving the understanding, recognition and management of these adverse events.

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Section: Aims and Methodsmentioning

confidence: 50%

Section: Aims and Methodsmentioning

confidence: 99%

Review article: managing the adverse events caused by anti‐TNF therapy in inflammatory bowel disease

Shivaji

Sharratt

Thomas

et al. 2019

Aliment Pharmacol Ther

107

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“…A negative effect of immunosuppressive therapy on the results of IGRA has also been shown in metaanalysis comprising of 71.5% of the patients who were on immunosuppressive treatment [25]. Use of corticosteroids and infliximab has shown to convert a positive QFT-GIT into negative of 30% of the study subjects tested [26]. Lowered lymphocyte counts are also found to be associated with indeterminate QFT-G results in patients with autoimmune disease [27].…”

Section: Discussionmentioning

confidence: 83%

Testing for Mycobacterium tuberculosis infection using the QuantiFERON-TB GOLD assay in patients with comorbid conditions in a tertiary care endemic setting

Masood

Jamil

Akber

et al. 2020

Trop Dis Travel Med Vaccines

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Introduction: There were 10 million new cases of tuberculosis (TB) in 2017. To eliminate TB, it is necessary to diagnose active TB and latent tuberculosis infection (LTBI). Diagnosis of paucibacillary disease and in extrapulmonary TB (EPTB) remains challenging; low mycobacterial load can be missed by microbiological or molecular based confirmation; EPTB, can be misdiagnosed due to absence of site specific specimens for testing. Interferon gamma release assays (IGRA) use T cell-based Interferon-gamma (IFN-γ) to identify infection with M. tuberculosis (MTB) but cannot discriminate between active and LTBI. We investigated how IGRA was being used in a high burden low resource setting. Methods: We conducted a retrospective review of 149 consecutive cases received for QuantiFERON-TB Gold In-Tube Assay (QFT-GIT) testing in routine clinical service. Results: Fifty-six cases were QFT-GIT positive and 93 were QFT-GIT negative. Thirty-six per cent of QFT-GIT tested cases had active TB. Of QFT-GIT positive cases, 59% patients had active TB; 10 with pulmonary and 23 with extrapulmonary TB. The remaining 41% QFT-positive cases were LTBI. Of the QFT-GIT negative cases, 22% had active TB. Co-morbid conditions were present in 37% of QFT-GIT positive and 60% of QFT-GIT negative cases. Conclusions: Our study shows that IGRA is being used as an adjunct test for active TB in this population. It highlights the complexity of interpreting QFT-GIT results particularly for QFT-GIT negative cases when ruling out MTB infection.

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“…[6,16] In 2017, Edwards et al conducted a study that used an ex vivo model to determine the in uence of corticosteroids and in iximab on the performance of QFT-GIT assays. [17] Both corticosteroids and in iximab were added after the blood was taken from the patient, the results of these assays were compared with the test results of patients' blood without added drugs. Both drugs impaired the QFT-GIT performance signi cantly.…”

Section: Immunosuppressive Medication and Indeterminate Test Resultsmentioning

confidence: 99%

Steroid therapy does not affect the rate of indeterminate results with the T-SPOT.TB interferon gamma release assay

Schulz

MacKenzie

2020

Preprint

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Background: The underlying causes of indeterminate (invalid) interferon-gamma release assays are not clear and predictors of indeterminate results do not exist. To date the effect of steroid concomitant therapy on the rate of indeterminate tests is unknown. Methods: We performed a retrospective analysis of the results of 1339 tests, including clinical data from patient records, of which 914 were suitable for complete data analysis.Results: 130 (15.2 %) tests were positive and 719 (83.8 %) were negative, 9 tests (1 %) were borderline positive (according to manufacturer’s definition). Indeterminate results (56 (6.1 %) arose from failure of the negative control in 24 (42.9 %) and failure of the positive control in 32 (57.1 %) tests. Of 914 patients, 196 were taking cortisone at the time of testing; among these patients 180 (91.8 %) returned a valid result and 16 (8.2 %) an indeterminate result compared to 40 indeterminate tests of 718 (5.6 %) results from patients not on corticosteroid therapy at the time of testing (p = 0.180), (relative risk [RR] 1.46, [95 % CI 0.84 to 2.56]). No significant difference in the rate of indeterminate results was found with immunosuppressive diseases or medications other than with HIV; among HIV-positive patients, 11 (11.7 %) had an indeterminate test result, compared to 45 (5.5 %) in HIV-negative individuals (p =0.017, relative risk [RR] 2.13, [95 % CI 1.14 to 3.98]).Conclusions: steroid therapy does not have an effect whereas HIV positivity has a negative effect on the number of indeterminate results in the T-Spot.TB test.

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Corticosteroids and infliximab impair the performance of interferon-γ release assays used for diagnosis of latent tuberculosis

Cited by 42 publications

References 22 publications

Review article: managing the adverse events caused by anti‐TNF therapy in inflammatory bowel disease

Review article: managing the adverse events caused by anti‐TNF therapy in inflammatory bowel disease

Testing for Mycobacterium tuberculosis infection using the QuantiFERON-TB GOLD assay in patients with comorbid conditions in a tertiary care endemic setting

Steroid therapy does not affect the rate of indeterminate results with the T-SPOT.TB interferon gamma release assay

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