Latent tuberculosis infection screening in patients with inflammatory bowel disease: a nationwide retrospective cohort study in South Korea comparing IGRA alone versus a combination of TST and IGRA

Ye-Jee Kim; Jiyeon Kim; Jiwon Lee; Tae Sun Shim; Sang Hyoung Park; Kyung-Wook Jo

doi:10.5217/ir.2025.00136

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Original Article IBD Latent tuberculosis infection screening in patients with inflammatory bowel disease: a nationwide retrospective cohort study in South Korea comparing IGRA alone versus a combination of TST and IGRA: Ye-Jee Kim^1,*, Jiyeon Kim^2,*, Jiwon Lee³, Tae Sun Shim⁴, Sang Hyoung Park⁵, Kyung-Wook Jo⁴; Intestinal Research 2025;23(4):541-550.
DOI: https://doi.org/10.5217/ir.2025.00136
Published online: October 14, 2025

¹Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

²Department of Internal Medicine, Seoul Medical Center, Seoul, Korea

³Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

⁴Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

⁵Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to Sang Hyoung Park, Division of Gastroenterology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. E-mail: shpark78@amc.seoul.kr

Co-Correspondence to Kyung-Wook Jo, Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. E-mail: siegmund@amc.seoul.kr

*These authors contributed equally to this study as first authors.

• Received: July 15, 2025 • Revised: August 27, 2025 • Accepted: September 2, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
NOTES
Supplementary Material
REFERENCES

Abstract

Background/Aims
We aimed to evaluate if using the interferon-gamma release assay (IGRA) alone is effective for latent tuberculosis infection (LTBI) screening in preventing active tuberculosis in patients with inflammatory bowel disease (IBD) before initiating anti-tumor necrosis factor alpha (anti-TNF-α) therapy, compared to using both the tuberculin skin test and IGRA.
Methods
Using South Korea’s Health Insurance Review and Assessment Service, we selected IBD patients treated with anti-TNF-α agents for ≥ 1 year who underwent LTBI screening between 2018 and 2021. We compared the 1-year incidence rate and standardized incidence ratio of active tuberculosis incidence after starting anti-TNF-α treatment to the general population based on the LTBI screening strategy.
Results
Of the 4,215 enrolled patients, 3,505 underwent IGRA alone for LTBI screening, while 710 received both tuberculin skin test and IGRA. Within 1 year of starting anti-TNF-α treatment, 15 patients (0.36%) developed active tuberculosis, with a mean follow-up period of 4,200.6 person-years. The 1-year tuberculosis incidence rates were 372.3 (95% confidence interval [CI], 198.2–636.6) per 100,000 person-years for the IGRA alone group and 282.3 (95% CI, 34.2–1,019.9) per 100,000 person-years for the combination group. The standardized incidence ratios were similar: 14.34 (95% CI, 7.63–24.52) for the IGRA alone group and 11.25 (95% CI, 1.26–40.61) for the combination group.
Conclusions
Using IGRA alone may be an effective strategy for LTBI screening in IBD patients before starting anti-TNF-α therapy. (Intest Res, Published online)
Keywords: Inflammatory bowel diseases; Tumor necrosis factor-alpha; Tuberculin skin test; Interferon-gamma release tests; Tuberculosis

INTRODUCTION

The introduction of monoclonal antibodies against tumor necrosis factor alpha (anti-TNF-α) agent marked a breakthrough in treating inflammatory bowel disease (IBD), leading to substantial improvements in patient outcomes, including sustained clinical remission, reduced complications, and restored quality of life [1]. However, since TNF is crucial for defending against Mycobacterium tuberculosis and maintaining granuloma integrity [2], anti-TNF-α therapy increases the risk of tuberculosis, predominantly through reactivating latent tuberculosis infection (LTBI) [3]. This is particularly concerning in countries where tuberculosis is endemic, as it represents the most severe infectious complication linked to anti-TNF-α treatment [4]. Thorough screening and treatment of LTBI before initiating TNF antagonists have significantly reduced tuberculosis incidence [5], making LTBI screening strongly recommended before anti-TNF-α therapy [6,7].

Current diagnostic tests for LTBI include the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). For screening LTBI in IBD patients, guidelines [8,9], including those from the European Crohn’s and Colitis Organisation (ECCO) [10], recommend a dual strategy using both TST and IGRA. However, some experts advocate using IGRA alone [11].

The TST has limitations, including false positives in patients vaccinated with Bacillus Calmette-Guérin (BCG) and the need for a follow-up visit 2 to 3 days later for result interpretation [12]. Therefore, if IGRA alone is sufficient for LTBI screening, it would be a more practical and useful strategy for IBD patients. Indeed, guidelines recommend performing IGRA alone in patients with inflammatory arthritis (e.g., rheumatoid arthritis) [13], supported by previous studies [14,15].

However, research on the feasibility of using IGRA alone for LTBI screening in patients with IBD is limited [16]. There have been no direct comparative studies between the 2 strategies (combining TST and IGRA vs. IGRA alone). The aim of this study was to determine whether using IGRA alone is an appropriate strategy for LTBI screening in terms of tuberculosis development in patients with IBD before initiating anti-TNF-α treatment, compared to the combination of TST and IGRA.

METHODS

1. Database

We analyzed data from South Korea’s Health Insurance Review and Assessment Service (HIRA) database in a country with an intermediate tuberculosis burden (49 cases per 100,000 population in 2020). HIRA, a government-affiliated body, covers 97% of the nation’s approximately 50 million residents, all enrolled in the National Health Insurance program. HIRA verifies National Health Insurance claims and reviews medical expenses, and healthcare provider reports to generate comprehensive health insurance claims data. This data includes diagnoses according to the International Classification of Diseases, 10th Revision (ICD-10), inpatient/outpatient status, demographics, procedures, medications, prescription dates and durations, and tests [17]. The data provided by HIRA were anonymized per the Personal Information Protection Act. The Institutional Review Board of Asan Medical Center approved the study protocol in Seoul, South Korea (IRB No. 2022-0977). Informed consent was waived as the study utilized an existing anonymized database.

2. Study Population

Since IGRA claim data has been included in the HIRA database from 2018, we obtained HIRA claims data from 2018 to 2021 for patients diagnosed with ulcerative colitis (UC) (ICD-10 codes K51.0–51.9) or Crohn’s disease (CD) (ICD-10 codes K50.0–50.9) treated with anti-TNF-α agents (infliximab, adalimumab, and golimumab). We excluded patients without rare intractable disease registration codes (V131 for UC, V130 for CD) [18] or whose ICD-10 codes for UC or CD were not listed in the principal or subsidiary diagnostic fields. Patients treated with anti-TNF-α therapy for <1 year were also excluded, as the primary objective was to analyze 1-year tuberculosis development after TNF antagonist treatment. After further excluding patients who had not undergone LTBI screening before anti- TNF-α therapy or received TST alone, we identified IBD patients treated with anti-TNF-α agents for ≥ 1 year and who underwent proper LTBI screening before TNF antagonist initiation between 2018 and 2021 (Fig. 1). We compared the incidence of tuberculosis after treatment initiation of anti-TNF-α agents according to the LTBI screening strategy (i.e., the combination of TST and IGRA vs. IGRA alone).

3. Analysis of Active Tuberculosis Development

A diagnosis of active tuberculosis was defined by a tuberculosis-related claim (ICD-10 codes A15–19, U88.0, U88.1, U84.3, U84.30, U84.31, U84.39) together with the prescription of at least one antituberculosis medication (isoniazid, rifamycin, ethambutol, pyrazinamide, prothionamide, cycloserine, paraaminosalicylic acid, levofloxacin, moxifloxacin, bedaquiline or linezolid) within 90 days of diagnosis [19]; detailed descriptions of these ICD-10 codes are provided in Supplementary Table 1. We excluded patients diagnosed with active tuberculosis within 2 years before starting biologic therapy (Fig. 1) [19]. Importantly, the same definition of active tuberculosis—including intestinal tuberculosis (A18.3)—was applied consistently to both case identification and exclusion criteria. Only cases where active tuberculosis occurred within 1 year of initiating anti-TNF-α therapy were considered treatment-related, as the probability of LTBI reactivation peaks within the first year of anti-TNF-α therapy [3,20]. All patients were evaluated for tuberculosis occurrence during the follow-up period, up to 1 year after the initiation of anti-TNF-α treatment. The enrollment period lasted until 2021, with the final follow-up date in December 2022.

4. LTBI Screening

Patients in the eligible cohort were diagnosed with LTBI if they were prescribed isoniazid, rifampicin, or both within 2 years before starting anti-TNF-α treatment [21]. Patients were considered to have undergone IGRA testing if they had any of the following tests: QuantiFERON-Gold-in-Tube (QIAGEN, Germantown, MD, USA), QuantiFERON-Gold-Plus (QIAGEN), or TSPOT-TB (Oxford Immunotec, Abingdon, UK).

5. Statistical Analysis

Categorical data were compared using the chi-square test, and continuous variables were analyzed using the independent t-test. Incidence rates were presented as the number of tuberculosis cases per 100,000 person-years over a 1-year follow-up. Confidence intervals (CIs) for incidence rates were estimated assuming a Poisson distribution. The risk of developing tuberculosis within 1 year was evaluated using the standardized incidence ratio (SIR) and its 95% CI for active tuberculosis. This involved dividing the observed number of tuberculosis cases by the expected number in the general population of South Korea, stratified by 5-year age groups and sex. The expected number of cases was based on the incidence rate of active tuberculosis from 2018 to 2022, as reported by the Korean Centers for Disease Control and Prevention [22].

The cumulative incidence of 1-year tuberculosis was evaluated using Kaplan-Meier curves, and risk factors were identified using the Cox proportional hazards regression with Firth’s penalized likelihood method. In the multivariate analyses, age, sex, LTBI screening strategy, and variables significant in the univariate analyses were included. P-values <0.05 were considered statistically significant. Statistical analyses were performed using the SAS Enterprise Guide (version 7.1; SAS Institute, Inc, Cary, NC, USA) and R software (version 3.5.1; R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

1. Study Patients

After applying the enrollment criteria, 4,215 participants were included in the study (Fig. 1). Patients with CD constituted 64.7% of the population, and 80.0% received concomitant steroid therapy. The most frequently prescribed anti-TNF-α agents were infliximab (n=2,852, 67.7%), followed by adalimumab (n =1,203, 28.5%), and golimumab (n =160, 3.8%). Of 4,215 patients, 3,505 underwent IGRA alone for LTBI screening, while the remaining 710 received a combination of TST and IGRA. Several characteristics, including age, the type of IBD, use of thiopurine or methotrexate, and comorbidity such as hypertension exhibited significant differences between the groups (Table 1).

2. LTBI Diagnosis

Among the 4,215 participants, 269 (6.4%) were diagnosed with LTBI based on claim data. The LTBI diagnosis rate was 9.0% in the TST and IGRA combination group. Compared to 5.8% in the IGRA alone group, there was a statistically significant higher rate in the combination group (P=0.002).

3. Incidence Rate of Active Tuberculosis

Of the 4,215 patients, 15 (0.36%) developed active tuberculosis within 1 year of starting anti-TNF-α agents treatment (clinical characteristics summarized in Supplementary Table 2). This occurred over a mean follow-up period of 4,200.6 person-years, resulting in an incidence rate of 357.1 (95% CI, 199.9–589.0) per 100,000 person-years (Table 2). In the IGRA alone group, 0.37% (13/3,505) developed tuberculosis, while in the TST and IGRA combination group, 0.28% (2/710) were diagnosed with tuberculosis within 1 year. The incidence rates were 372.3 (95% CI, 198.2–636.6) and 282.3 (95% CI, 34.2–1,019.9) per 100,000 person-years, respectively. Fig. 2 presents the Kaplan-Meier analysis of 1-year tuberculosis development after the initiating TNF antagonists, showing no statistically significant difference between the 2 groups (P=0.717).

4. SIR of Active Tuberculosis

Table 3 presents the SIRs of study patients. The overall 1-year tuberculosis incidence, adjusted for sex and age, was significantly higher than in the general population (SIR, 13.83; 95% CI, 7.73–22.81). The LTBI screening strategy was not significantly associated with the SIR of 1-year active tuberculosis development (IGRA alone group: SIR, 14.34; 95% CI, 7.63–24.52; TST and IGRA group: SIR, 11.25; 95% CI, 1.26–40.61).

5. Risk Factors of Tuberculosis Development

Univariate analysis revealed that the LTBI screening strategy was not associated with the risk of tuberculosis development within 1 year after anti-TNF-α agent initiation (Table 4). The hazard ratio for patients with IBD screened with IGRA alone was 1.10 (95% CI, 0.33–5.56) compared to those screened with both TST and IGRA. Several covariates, including the type of IBD and comorbidities such as the Charlson Comorbidity Index (CCI) were associated with 1-year tuberculosis development in univariate analyses. Multivariate analysis results are presented in Table 5. The LTBI screening strategy was not significantly associated with the risk of tuberculosis development (hazard ratio, 1.09; 95% CI, 0.33–5.56), whereas the CCI remained independently associated with an increased risk of tuberculosis development.

DISCUSSION

We evaluated whether using IGRA alone is acceptable for LTBI screening in patients with IBD compared to combining TST and IGRA by analyzing population-based cohort data from nationwide administrative claims data in South Korea. The main result was that for patients with IBD requiring LTBI screening before initiating anti-TNF-α treatment, IGRA alone without concurrent TST is an acceptable strategy, as there is no significant difference in the 1-year incidence of active tuberculosis between using IGRA alone and the combination of TST and IGRA.

In our study cohort, the proportion of patients diagnosed with LTBI was significantly higher in the TST and IGRA combination group compared to the IGRA-alone group. This supports existing guidelines recommending both tests for immunocompromised patients [8,9], including those with IBD undergoing biologics therapy [10], to enhance LTBI diagnosis sensitivity. Despite fewer LTBI diagnoses in the IGRA-alone group, there was no difference in the 1-year incidence of tuberculosis, suggesting that positive TST and negative IGRA results may be due to TST false positives. South Korea mandates BCG vaccination at 4 weeks of age [23], and individuals who received BCG vaccination are more likely to have false positive TST results [24]. Younger patients in our cohort more frequently underwent screening with both TST and IGRA (Supplementary Fig. 1). Although the influence of a single BCG vaccination at infancy diminishes after 15 years [25], South Koreans born before 1985 who had a negative TST at age 12 were re-vaccinated. Mancuso et al. [26] reported that BCG vaccination after infancy increased TST reactivity risk up to 55 years later. This BCG-induced TST false positivity likely contributed to the higher LTBI treatment rate in the TST and IGRA combination group despite no difference in tuberculosis incidence.

Another important reason is that IGRA may be more accurate than TST in predicting the progression of LTBI to active tuberculosis. Although there is controversy over which test is superior for LTBI screening, many studies indicate that IGRA has a better predictive ability for tuberculosis development and is more effective in identifying patients who would benefit from preventive treatment compared to TST [27,28]. A recent systematic review and meta-analysis of 40 studies found that IGRA has a significantly higher predictive power (pooled relative risk) and positive/negative predictive value than TST for predicting LTBI progression to active tuberculosis [29]. These findings suggest that adding TST provides little additional benefit over using IGRA alone, which is consistent with the results of the present study.

LTBI screening is strongly recommended before initiating TNF antagonist therapy for inflammatory arthritis, including rheumatoid arthritis and ankylosing spondylitis [30]. Notably, a number of studies indicate that combining IGRA with TST may be unnecessary, as dual testing offers no significant benefit over IGRA alone [14,15,31]. Consequently, the 2022 European League Against Rheumatism guidelines prefer IGRA alone for LTBI screening in patients with autoimmune inflammatory rheumatic diseases [13]. Although ECCO guidelines recommend combining TST and IGRA [10], there is limited evidence supporting this approach due to the lack of research on LTBI screening strategies focused on IBD. Our study is the first to indicate that, similar to patients with inflammatory arthritis, IGRA alone may be sufficient for LTBI screening in IBD patients.

It is well-known that even after appropriate LTBI screening and treatment, patients with IBD may have a higher rate of tuberculosis development than the general population. This is mainly attributed to the incomplete sensitivity of LTBI screening tests or the suboptimal effectiveness of preventive treatment [32,33]. We previously reported that patients with IBD receiving TNF inhibitors had a higher incidence of 1-year tuberculosis compared to the general population, regardless of their LTBI status, after assessing 740 patients treated at our institution between 2011 and 2017 [3]. In that study, the overall SIR of total patients was 14.0 (95% CI, 7.0–28.0), which is similar to the SIR observed in the present study.

In the multivariate analysis, the CCI was identified as the only significant risk factor for tuberculosis development. The CCI is a widely used composite measure that reflects the burden of chronic comorbid conditions and has been validated as a predictor of mortality and other adverse outcomes across diverse clinical settings [34]. Our findings suggest that the overall comorbidity burden, rather than the LTBI screening strategy, is the more important determinant of susceptibility to active tuberculosis among patients with IBD treated with anti-TNF-α agents. This highlights the need for careful monitoring and preventive strategies against tuberculosis in patients with IBD who present with multiple comorbidities.

This study had certain limitations. First, the number of patients who underwent the combined TST and IGRA test was significantly lower than those who tested IGRA alone. Second, we could not evaluate unobserved confounders, especially those related to the attending physician’s LTBI screening strategies. Moreover, detailed information on TST or IGRA test results (positive or negative) and patient adherence to prescribed medications were not accessible in the HIRA data. Finally, as this study was based on an administrative claims database, we could not assess subjective or objective disease activity of IBD.

In conclusion, for IBD patients requiring LTBI screening before initiating anti-TNF-α agent treatment, using IGRA alone without concurrent TST is an acceptable strategy, considering there is no significant difference in the 1-year incidence of active tuberculosis between testing IGRA alone and the combination of TST and IGRA.

NOTES

Funding Source

Jo KW received a research grant from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea (grant number 2025IL0020). Park SH received a research grant from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea (grant number 2023IT0006).

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability Statement

Data analyzed in this study are available from the corresponding author upon reasonable request.

Author Contributions

Conceptualization: all authors. Data curation: all authors. Formal analysis: all authors. Funding acquisition: Park SH, Jo KW. Investigation: all authors. Methodology: Kim YJ, Kim J, Park SH, Jo KW. Validation: Park SH. Writing-original draft: Kim YJ, Kim J, Lee J, Park SH, Jo KW. Writing-review & editing: Kim YJ, Kim J, Shim TS, Park SH, Jo KW. Approval of final manuscript: all authors.

Supplementary Material

Supplementary materials are available at the Intestinal Research website (https://www.irjournal.org).

Supplementary Table 1.

Detailed ICD-10 Codes Used to Define Active Tuberculosis (Based on ICD-10 and Korean Extension Codes)

ir-2025-00136-Supplementary-Table-1.pdf

Supplementary Table 2.

The Clinical Characteristics of 15 Patients Diagnosed with Active Tuberculosis

ir-2025-00136-Supplementary-Table-2.pdf

Supplementary Fig. 1.

The proportion of each latent tuberculosis infection screening strategy by age group. IGRA, interferon-gamma release assay; TST, tuberculin skin test.

ir-2025-00136-Supplementary-Fig-1.pdf

Fig. 1.

Patient selection flowchart. IBD, inflammatory bowel disease; TNF, tumor necrosis factor; LTBI, latent tuberculosis infection; TST, tuberculin skin test; IGRA, interferon-gamma release assay.

Fig. 2.

Kaplan-Meier plot of the risk of 1-year tuberculosis incidence of the IGRA alone versus TST and IGRA group. IGRA, interferon-gamma release assay; TST, tuberculin skin test; TNF, tumor necrosis factor.

Table 1.

Baseline Characteristics of Patients with IBD According to the Latent Tuberculosis Infection Screening Strategy

Characteristic	Total patients (n=4,215)	IGRA alone (n=3,505)	TST and IGRA (n=710)	P-value
Age (yr)				0.001
10–19	778 (18.5)	614 (17.5)	164 (23.1)
20–39	2,279 (54.1)	1,902 (54.3)	377 (53.1)
40–59	859 (20.4)	724 (20.7)	135 (19.0)
≥ 60	299 (7.1)	264 (7.6)	34 (4.8)
Sex				0.193
Male	3,000 (71.2)	2,509 (71.6)	491 (69.2)
Female	1,215 (28.8)	996 (28.4)	219 (30.8)
Health insurance type				0.609
Health insurance	4,121 (97.8)	3,425 (97.7)	696 (98.0)
Medicaid	94 (2.2)	80 (2.3)	14 (2.0)
Type of IBD				0.024
Crohn’s disease	2,728 (64.7)	2,242 (64.0)	486 (68.5)
Ulcerative colitis	1,296 (30.7)	1,108 (31.6)	188 (26.5)
Unspecified	191 (4.5)	155 (4.4)	36 (5.1)
Use of immunomodulatory drug
Corticosteroids	3,373 (80.0)	2,815 (80.3)	558 (78.6)	0.295
Thiopurine	3,121 (74.0)	2,539 (72.4)	582 (82.0)	< 0.001
Methotrexate	189 (4.5)	134 (3.8)	55 (7.7)	< 0.001
Comorbidities
CCI, mean ± SD	0.58 ± 0.97	0.58 ± 0.98	0.60 ± 0.95	0.659
CCI				0.495
0	2,601 (61.7)	2,176 (62.1)	425 (59.9)
1	1,105 (26.2)	907 (25.9)	198 (27.9)
≥2	509 (12.1)	422 (12.0)	87 (12.3)
Hypertension	272 (6.5)	239 (6.8)	33 (4.6)	0.032
Diabetes mellitus	184 (4.4)	161 (4.6)	23 (3.2)	0.107
Cancer	34 (0.8)	27 (0.8)	7 (1.0)	0.558
Chronic kidney disease	14 (0.3)	13 (0.4)	1 (0.1)	0.488
Organ transplantation	9 (0.2)	5 (0.1)	4 (0.6)	0.050
Chronic respiratory disease	164 (3.9)	134 (3.8)	30 (4.2)	0.613

Values are presented as number (%) unless otherwise indicated.

IBD, inflammatory bowel disease; IGRA, interferon-gamma release assay; TST, tuberculin skin test; CCI, Charlson Comorbidity Index; SD, standard deviation.

Table 2.

The Risk of 1-Year Tuberculosis in Patients with Inflammatory Bowel Disease Who Received Anti-Tumor Necrosis Factor-α Agents According to the Latent Tuberculosis Infection Screening Strategy

	Total patient (n = 4,215)	IGRA alone (n = 3,505)	TST and IGRA (n = 710)
1-Year tuberculosis development, No. (%)	15 (0.36)	13 (0.37)	2 (0.28)
Follow-up duration (sum of years)	4,200.6	3,492.2	708.4
Incidence rate/100,000 PY (95% CI)	357.1 (199.9–589.0)	372.3 (198.2–636.6)	282.3 (34.2–1,019.9)

IGRA, interferon-gamma release assay; TST, tuberculin skin test; PY, person-years; CI, confidence interval.

Table 3.

Standardized Incidence Ratio of 1-Year Tuberculosis According to the Latent Tuberculosis Infection Screening Strategy

	Total patients (n = 4,215)	IGRA alone (n = 3,505)	TST and IGRA (n = 710)
1-Year tuberculosis development, No. (%)	15 (0.36)	13 (0.37)	2 (0.28)
Expected development of tuberculosis	1.0846	0.9068	0.1778
Standardized incidence ratio (95% CI)	13.83 (7.73–22.81)	14.34 (7.63–24.52)	11.25 (1.26–40.61)

IGRA, interferon-gamma release assay; TST, tuberculin skin test; CI, confidence interval.

Table 4.

Risk Factor of 1-Year Tuberculosis Development of Patients with IBD Treated with Anti-Tumor Necrosis Factor-α Agent

Variable	Total patients	Event, No. (%)	Follow-up duration (sum of years)	Incidence rate	HR (95% CI)	P-value
LTBI screening strategy						0.899
TST and IGRA	710	2 (0.28)	708.4	282.3	1
IGRA alone	3,505	13 (0.37)	3,492.2	372.3	1.10 (0.33–5.56)
Age (yr)
10–19	778	2 (0.26)	776.3	257.6	1
20–39	2,279	6 (0.26)	2,272.3	264.0	0.89 (0.23–4.83)	0.881
40–59	859	5 (0.58)	854.8	585.0	2.00 (0.48–11.10)	0.395
≥ 60	299	2 (0.67)	297.2	672.9	2.61 (0.40–16.86)	0.315
Sex
Male	3,000	12 (0.40)	2,988.3	401.6	1
Female	1,215	3 (0.25)	1,212.2	247.5	0.69 (0.18–2.05)	0.553
Health insurance type
Health insurance	4,121	14 (0.34)	4,107.6	340.8	1
Medicaid	94	1 (1.06)	93.0	1,075.4	4.57 (0.50–18.48)	0.086
Type of IBD
Crohn’s disease	2,728	6 (0.22)	2,721.6	220.5	1
Ulcerative colitis	1,296	9 (0.69)	1,288.1	698.7	3.08 (1.15–8.82)	0.035
Unspecified	191	0	190.9	0	1.10 (0.01–9.28)	0.952
Use of immunomodulatory drug
Corticosteroids	3,373	15 (0.44)	3,359.2	446.5	7.76 (1.05–989.92)	0.168
Thiopurine	3,121	11 (0.35)	3,110.1	353.7	0.90 (0.32–3.00)	0.848
Methotrexate	189	1 (0.53)	188.0	531.9	2.21 (0.24–8.92)	0.372
Comorbidities
CCI
0	2,601	4 (0.15)	2,596.6	154.0	1
1	1,105	7 (0.63)	1,098.3	637.3	3.93 (1.25–13.89)	0.029
≥2	509	4 (0.79)	505.6	791.1	5.13 (1.33–19.88)	0.019
Hypertension	272	3 (1.10)	269.9	1,111.5	4.07 (1.04–12.08)	0.025
Diabetes mellitus	184	1 (0.54)	183.0	546.6	2.27 (0.25–9.19)	0.354
Cancer	34	0	34.0	0	3.96 (0.03–29.36)	0.354
Chronic kidney disease	14	2 (14.29)	12.1	16,482.4	63.04 (12.39–207.65)	< 0.001
Organ transplantation	9	0	9.0	0	15.05 (0.12–111.56)	0.068
Chronic respiratory disease	164	1 (0.61)	162.9	631.8	2.57 (0.28–10.38)	0.287

HRs and P-values were calculated using Cox regression with Firth’s penalized likelihood method.

IBD, inflammatory bowel disease; HR, hazard ratio; CI, confidence interval; LTBI, latent tuberculosis infection; TST, tuberculin skin test; IGRA, interferongamma release assay; CCI, Charlson Comorbidity Index.

Table 5.

Multivariable Analysis Identifying Risk Factors for 1-Year Tuberculosis Development in Patients with IBD Treated with Anti-Tumor Necrosis Factor-α Agents

Variable	Hazard ratio (95% CI)	P-value
LTBI screening strategy		0.907
TST and IGRA	1
IGRA alone	1.09 (0.33–5.56)
Age (yr)
10–19	1
20–39	0.77 (0.19–4.25)	0.749
40–59	1.03 (0.20–6.41)	0.978
≥ 60	0.67 (0.07–5.97)	0.729
Sex
Male	1
Female	0.59 (0.15–1.76)	0.398
Type of IBD
Crohn’s disease	1
Ulcerative colitis	5.46 (0.81–7.80)	0.130
Unspecified	0.89 (0.01–7.67)	0.939
Comorbidities
CCI
0	1
1	3.61 (1.13–12.91)	0.044
≥2	4.06 (0.93–17.17)	0.063
Hypertension	1.92 (0.41–7.74)	0.389

Although chronic kidney disease was significant in the univariate analysis, the hazard ratio estimate was highly unstable—with the upper bound of the 95% confidence interval exceeding 100—and was therefore excluded from the multivariate model. Hazard ratios and P-values were calculated using Cox regression with Firth’s penalized likelihood method.

IBD, inflammatory bowel disease; CI, confidence interval; LTBI, latent tuberculosis infection; TST, tuberculin skin test; IGRA, interferon-gamma release assay; CCI, Charlson Comorbidity Index.

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Latent tuberculosis infection screening in patients with inflammatory bowel disease: a nationwide retrospective cohort study in South Korea comparing IGRA alone versus a combination of TST and IGRA

Intest Res. 2025;23(4):541-550. Published online October 14, 2025

DOI: https://doi.org/10.5217/ir.2025.00136

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Latent tuberculosis infection screening in patients with inflammatory bowel disease: a nationwide retrospective cohort study in South Korea comparing IGRA alone versus a combination of TST and IGRA

Fig. 1. Patient selection flowchart. IBD, inflammatory bowel disease; TNF, tumor necrosis factor; LTBI, latent tuberculosis infection; TST, tuberculin skin test; IGRA, interferon-gamma release assay.

Fig. 2. Kaplan-Meier plot of the risk of 1-year tuberculosis incidence of the IGRA alone versus TST and IGRA group. IGRA, interferon-gamma release assay; TST, tuberculin skin test; TNF, tumor necrosis factor.

Fig. 1.

Fig. 2.

Latent tuberculosis infection screening in patients with inflammatory bowel disease: a nationwide retrospective cohort study in South Korea comparing IGRA alone versus a combination of TST and IGRA

Characteristic	Total patients (n=4,215)	IGRA alone (n=3,505)	TST and IGRA (n=710)	P-value
Age (yr)				0.001
10–19	778 (18.5)	614 (17.5)	164 (23.1)
20–39	2,279 (54.1)	1,902 (54.3)	377 (53.1)
40–59	859 (20.4)	724 (20.7)	135 (19.0)
≥ 60	299 (7.1)	264 (7.6)	34 (4.8)
Sex				0.193
Male	3,000 (71.2)	2,509 (71.6)	491 (69.2)
Female	1,215 (28.8)	996 (28.4)	219 (30.8)
Health insurance type				0.609
Health insurance	4,121 (97.8)	3,425 (97.7)	696 (98.0)
Medicaid	94 (2.2)	80 (2.3)	14 (2.0)
Type of IBD				0.024
Crohn’s disease	2,728 (64.7)	2,242 (64.0)	486 (68.5)
Ulcerative colitis	1,296 (30.7)	1,108 (31.6)	188 (26.5)
Unspecified	191 (4.5)	155 (4.4)	36 (5.1)
Use of immunomodulatory drug
Corticosteroids	3,373 (80.0)	2,815 (80.3)	558 (78.6)	0.295
Thiopurine	3,121 (74.0)	2,539 (72.4)	582 (82.0)	< 0.001
Methotrexate	189 (4.5)	134 (3.8)	55 (7.7)	< 0.001
Comorbidities
CCI, mean ± SD	0.58 ± 0.97	0.58 ± 0.98	0.60 ± 0.95	0.659
CCI				0.495
0	2,601 (61.7)	2,176 (62.1)	425 (59.9)
1	1,105 (26.2)	907 (25.9)	198 (27.9)
≥2	509 (12.1)	422 (12.0)	87 (12.3)
Hypertension	272 (6.5)	239 (6.8)	33 (4.6)	0.032
Diabetes mellitus	184 (4.4)	161 (4.6)	23 (3.2)	0.107
Cancer	34 (0.8)	27 (0.8)	7 (1.0)	0.558
Chronic kidney disease	14 (0.3)	13 (0.4)	1 (0.1)	0.488
Organ transplantation	9 (0.2)	5 (0.1)	4 (0.6)	0.050
Chronic respiratory disease	164 (3.9)	134 (3.8)	30 (4.2)	0.613

	Total patient (n = 4,215)	IGRA alone (n = 3,505)	TST and IGRA (n = 710)
1-Year tuberculosis development, No. (%)	15 (0.36)	13 (0.37)	2 (0.28)
Follow-up duration (sum of years)	4,200.6	3,492.2	708.4
Incidence rate/100,000 PY (95% CI)	357.1 (199.9–589.0)	372.3 (198.2–636.6)	282.3 (34.2–1,019.9)

	Total patients (n = 4,215)	IGRA alone (n = 3,505)	TST and IGRA (n = 710)
1-Year tuberculosis development, No. (%)	15 (0.36)	13 (0.37)	2 (0.28)
Expected development of tuberculosis	1.0846	0.9068	0.1778
Standardized incidence ratio (95% CI)	13.83 (7.73–22.81)	14.34 (7.63–24.52)	11.25 (1.26–40.61)

Variable	Total patients	Event, No. (%)	Follow-up duration (sum of years)	Incidence rate	HR (95% CI)	P-value
LTBI screening strategy						0.899
TST and IGRA	710	2 (0.28)	708.4	282.3	1
IGRA alone	3,505	13 (0.37)	3,492.2	372.3	1.10 (0.33–5.56)
Age (yr)
10–19	778	2 (0.26)	776.3	257.6	1
20–39	2,279	6 (0.26)	2,272.3	264.0	0.89 (0.23–4.83)	0.881
40–59	859	5 (0.58)	854.8	585.0	2.00 (0.48–11.10)	0.395
≥ 60	299	2 (0.67)	297.2	672.9	2.61 (0.40–16.86)	0.315
Sex
Male	3,000	12 (0.40)	2,988.3	401.6	1
Female	1,215	3 (0.25)	1,212.2	247.5	0.69 (0.18–2.05)	0.553
Health insurance type
Health insurance	4,121	14 (0.34)	4,107.6	340.8	1
Medicaid	94	1 (1.06)	93.0	1,075.4	4.57 (0.50–18.48)	0.086
Type of IBD
Crohn’s disease	2,728	6 (0.22)	2,721.6	220.5	1
Ulcerative colitis	1,296	9 (0.69)	1,288.1	698.7	3.08 (1.15–8.82)	0.035
Unspecified	191	0	190.9	0	1.10 (0.01–9.28)	0.952
Use of immunomodulatory drug
Corticosteroids	3,373	15 (0.44)	3,359.2	446.5	7.76 (1.05–989.92)	0.168
Thiopurine	3,121	11 (0.35)	3,110.1	353.7	0.90 (0.32–3.00)	0.848
Methotrexate	189	1 (0.53)	188.0	531.9	2.21 (0.24–8.92)	0.372
Comorbidities
CCI
0	2,601	4 (0.15)	2,596.6	154.0	1
1	1,105	7 (0.63)	1,098.3	637.3	3.93 (1.25–13.89)	0.029
≥2	509	4 (0.79)	505.6	791.1	5.13 (1.33–19.88)	0.019
Hypertension	272	3 (1.10)	269.9	1,111.5	4.07 (1.04–12.08)	0.025
Diabetes mellitus	184	1 (0.54)	183.0	546.6	2.27 (0.25–9.19)	0.354
Cancer	34	0	34.0	0	3.96 (0.03–29.36)	0.354
Chronic kidney disease	14	2 (14.29)	12.1	16,482.4	63.04 (12.39–207.65)	< 0.001
Organ transplantation	9	0	9.0	0	15.05 (0.12–111.56)	0.068
Chronic respiratory disease	164	1 (0.61)	162.9	631.8	2.57 (0.28–10.38)	0.287

Variable	Hazard ratio (95% CI)	P-value
LTBI screening strategy		0.907
TST and IGRA	1
IGRA alone	1.09 (0.33–5.56)
Age (yr)
10–19	1
20–39	0.77 (0.19–4.25)	0.749
40–59	1.03 (0.20–6.41)	0.978
≥ 60	0.67 (0.07–5.97)	0.729
Sex
Male	1
Female	0.59 (0.15–1.76)	0.398
Type of IBD
Crohn’s disease	1
Ulcerative colitis	5.46 (0.81–7.80)	0.130
Unspecified	0.89 (0.01–7.67)	0.939
Comorbidities
CCI
0	1
1	3.61 (1.13–12.91)	0.044
≥2	4.06 (0.93–17.17)	0.063
Hypertension	1.92 (0.41–7.74)	0.389

Table 1. Baseline Characteristics of Patients with IBD According to the Latent Tuberculosis Infection Screening Strategy

Values are presented as number (%) unless otherwise indicated.

IBD, inflammatory bowel disease; IGRA, interferon-gamma release assay; TST, tuberculin skin test; CCI, Charlson Comorbidity Index; SD, standard deviation.

Table 2. The Risk of 1-Year Tuberculosis in Patients with Inflammatory Bowel Disease Who Received Anti-Tumor Necrosis Factor-α Agents According to the Latent Tuberculosis Infection Screening Strategy

IGRA, interferon-gamma release assay; TST, tuberculin skin test; PY, person-years; CI, confidence interval.

Table 3. Standardized Incidence Ratio of 1-Year Tuberculosis According to the Latent Tuberculosis Infection Screening Strategy

IGRA, interferon-gamma release assay; TST, tuberculin skin test; CI, confidence interval.

Table 4. Risk Factor of 1-Year Tuberculosis Development of Patients with IBD Treated with Anti-Tumor Necrosis Factor-α Agent

HRs and P-values were calculated using Cox regression with Firth’s penalized likelihood method.

Table 5. Multivariable Analysis Identifying Risk Factors for 1-Year Tuberculosis Development in Patients with IBD Treated with Anti-Tumor Necrosis Factor-α Agents

IBD, inflammatory bowel disease; CI, confidence interval; LTBI, latent tuberculosis infection; TST, tuberculin skin test; IGRA, interferon-gamma release assay; CCI, Charlson Comorbidity Index.