Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases

Hatzara, Chrisoula; Hadziyannis, Emilia; Kandili, Anna; Koutsianas, Christos; Makris, Anastasia; Georgiopoulos, Georgios; Vassilopoulos, Dimitrios

doi:10.1136/annrheumdis-2014-205376

Cited by 53 publications

(51 citation statements)

References 25 publications

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“…In contrast to the result of no occurrence of TB observed in treated QFT-G converters in one Greek study [17], 7 (13%) of our untreated converters developed active TB. This discrepancy might be due to 1) the differences in the characteristics of the enrolled patients (with versus without INHP); and 2) the difference in the prevalence of active TB (49.4/100,000 Taiwan populations versus 5.0/100,000 Greece populations).…”

Section: Discussioncontrasting

confidence: 99%

“…Similar to a recent study showing frequent conversion of LTBI screening tests in RA patients receiving biologic therapy [17,33], 28.9% of our RA patients had QFT-G conversion during one-year biologic therapy using follow-up IFN-γ≧0.35 IU/ml as the criteria. In contrast to the result of no occurrence of TB observed in treated QFT-G converters in one Greek study [17], 7 (13%) of our untreated converters developed active TB.…”

Section: Discussionsupporting

confidence: 86%

“…However, Hatzara et al . demonstrated that no rheumatic patients developed active TB during follow-up in spite of frequent QFT-G conversion [17]. Therefore, there is an urgent need to identify candidate markers for effectively detecting active TB in QFT-G converters during the period of biologic therapy.…”

Section: Introductionmentioning

confidence: 99%

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Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy

Chen

Chen³

et al. 2016

PLoS ONE

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QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 86%

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Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy

Chen

Chen³

et al. 2016

PLoS ONE

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“…Because patients with RA may have false-negative IGRA or TST results due to immunosuppression, a negative IGRA or TST should not be interpreted as excluding the possibility that a patient has LTBI [89]. However, approximately one-third of patients with negative baseline TB screening develop conversion of TB screening during anti-TNF treatment [119]. So, if a patient with negative baseline TB screening develops active TB during biological therapy, two possibilities exist, either a false-negative IGRA or TST results or de novo TB infection.…”

Section: Preventionmentioning

confidence: 97%

Biological agents and respiratory infections: Causative mechanisms and practice management

Takayanagi

2015

Respiratory Investigation

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“…Recent studies, however, have shown that TB conversions may occur during anti-TNF therapy in ~10% of RA patients. [24] It is unclear if these conversions always represent 'true conversions' . More data are needed to make recommendations regarding rescreening in the absence of definite TB exposure.…”

Section: Tuberculosismentioning

confidence: 99%

Infections in the management of rheumatic diseases: An update

Botha-Scheepers¹,

Sarembock²

2015

S Afr Med J

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Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases

Abstract: Approximately one third of patients with negative baseline TB screening develop conversion of at least one screening test during anti-TNF treatment. These findings should be considered when designing re-screening strategies and contemplating latent TB therapy.

Cited by 53 publications

References 25 publications

Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy

Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy

Biological agents and respiratory infections: Causative mechanisms and practice management

Infections in the management of rheumatic diseases: An update

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