Background/Purpose: Anti-tumor necrosis factor alpha (Anti-TNFα) therapy is often used in patients with rheumatic diseases who do not respond to conventional treatment. Risk of tuberculosis infection is high in patients receiving anti-TNFα treatments. Therefore, tuberculosis infection prophylaxes are recommended prior to anti-TNFα therapy if a tuberculin skin test or interferon-gamma release assay (IGRA) is positive. However, little data is available on the conversion of IGRAs in patients with rheumatic diseases who received anti-TNF treatment. We evaluated the utility of follow-up IGRAs for the diagnosis of latent tuberculosis infection and newly developing tuberculosis in patients receiving TNFα antagonists.

Methods: The study participants (n=117) were enrolled from September 2008 to August 2012, among ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients registered in tertiary care center. These patients had a negative IGRA screening before receiving anti-TNFα therapy and were evaluated by follow-up IGRA for detection of latent and newly developing tuberculosis until May 2013. We retrospectively examined data of the subjects according to age, gender, tuberculosis prophylaxis, IGRA conversion and TNFα blockers, including type and treatment duration. The QuantiFERON-TB Gold In-Tube test was used for the initial and follow-up screenings to detect tuberculosis infection.

Results: The median interval between initial and follow-up IGRAs in patients was 20.5 months, and the median age was 38.9 years. Of the 117 patients (92 AS and 25 RA), 105 patients (89.7%) showed consistently negative results, and IGRA conversion was found in 12 patients (10.3%). Among the 92 AS patients, IGRA conversion was found in 7 patients (7.6 %). Among the 25 RA patients, 5 patients with positive conversion (20%) were found. One RA patient developed extrapulmonary tuberculosis. IGRA conversion rate was higher in older patients (≥ 40 years) (24.4%) than it was in younger patients (< 40 years) (1.4%) (p < 0.05) (Table 1). AS patients were younger and used anti-TNFα inhibitors for extended time period. IGRA conversion rate was not significantly different between AS (7.6%) and RA (20%) (p =0.13).

Conclusion: In patients with rheumatic diseases receiving TNFα blocker, IGRA conversions were observed. Patients with old age had higher IGRA conversion rate than patients with young age. These data suggest that follow-up IGRAs may identify false negative results of screening test and detect latent tuberculosis reactivation and new developing tuberculosis in patients receiving TNFα blockers in Korea. Larger-scaled studies may be needed for further evaluation about follow-up IGRAs.

Table 1. Patients characteristics and interferon-gamma release assay (IGRA) conversion rate.

Characteristics	All (N=117)		Conversion (N=12)		Adjusted OR	95% CI		p-value
Diagnosis
AS	92	(78.63)	7	(7.61)	0.42	(0.06 – 3.07)		0.394
RA	25	(21.37)	5	(20.00)	1.00
Age, yrs, mean (SD)
<40	72	(61.54)	1	(1.39)	1.00
≥ 40	45	(38.46)	11	(24.44)	21.19	(2.12 – 211.57)		0.009*
Gender
Male	76	(64.96)	6	(7.89)	1.00
Female	41	(35.04)	6	(14.63)	0.34	(0.05 – 2.30)		0.271
TNFα antagonists
Etanercept	43	(36.75)	7	(16.28)	1.00
Adalimumab	37	(31.62)	1	(2.70)	0.19	(0.02 – 1.96)		0.164
Infliximab	37	(31.62)	4	(10.81)	0.53	(0.11 – 2.47)		0.418
Duration of TNFα inhibitor therapy
< 2 yrs	74	(63.25)	5	(6.76)	1.00
≥ 2 yrs	43	(36.75)	7	(16.28)	2.31	(0.46 – 11.70)		0.313
Tuberculosis prophylaxis
No	102	(87.18)	8	(7.84)	1.00
Yes	15	(12.82)	4	(26.67)	1.70	(0.25 – 11.54)		0.590

^*p < 0.05

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/follow-up-testing-of-interferon-gamma-release-assays-for-the-diagnosis-of-hidden-tuberculosis-infection-in-patients-receiving-tumor-necrosis-factor-alpha-antagonists/