Highlight
– Pretreatment screening with QuantiFERON-TB (QFT) Gold alone significantly reduced TB infection diagnoses and preventive therapy prescriptions compared to dual testing.
– Incident TB during biologic therapy remained low (0.8%), with most cases occurring within the first two years of treatment.
– Routine periodic TB retesting after a negative baseline screen appears unnecessary in the absence of new exposures.
Study Background and Disease Burden
Biologic therapies have revolutionized treatment for immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, these immunomodulatory agents increase the risk of reactivating latent tuberculosis infection (LTBI) or acquiring new tuberculosis (TB) infection. TB remains a global health burden, and preventing TB reactivation in patients starting biologic therapies is critical.
Traditional TB screening involves the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) such as the QuantiFERON-TB Gold (QFT) assay. Dual screening strategies have been advocated for enhanced sensitivity but may result in overdiagnosis, increased preventive therapy use, and associated toxicity. Moreover, the optimal approach for periodic retesting during biologic therapy is unclear.
This study addresses the unmet need to optimize TB screening strategies to minimize unnecessary treatments without compromising safety.
Study Design
Researchers conducted a retrospective cohort study encompassing 1368 patients with immune-mediated inflammatory diseases screened for TB infection before biologic therapy initiation, using evolving diagnostic strategies over four periods spanning 2003 to 2020:
– Period 1 (2003–2006, n=184): Two-step TST alone
– Period 2 (2006–2008, n=129): Two-step TST plus QFT Gold
– Period 3 (2008–2014, n=427): Single-step TST plus QFT Gold
– Period 4 (2015–2020, n=628): QFT Gold alone
Patients with positive TB screening were offered preventive therapy, while those testing negative were not routinely retested unless newly exposed to TB. The primary endpoint was incident active TB during biologic therapy, as confirmed by nucleic acid amplification, culture, or compatible clinical and radiologic findings.
Key Findings
Overall, 23.9% of patients were diagnosed with latent TB infection (LTBI) across all periods. Importantly, the proportion decreased significantly from 40.8% in the earliest period (two-step TST alone) to 14.8% with QFT Gold alone (period 4) (P=.000 for trend). This trend was concomitant with a marked reduction in preventive therapy prescriptions.
Adjusted analysis demonstrated that the odds of TB infection diagnosis in period 4 were 77% lower than in period 1 (adjusted odds ratio, 0.23; 95% confidence interval [CI], 0.15-0.36).
Active TB developed in only 0.8% of patients, predominantly within the first two years after starting biologics. The probability of remaining TB-free after 11 years of biologic therapy was 99.1%.
Notably, among patients who tested negative at baseline and did not receive preventive therapy, most incident TB cases occurred within the first year of biologic therapy, suggesting that routine rescreening later in the treatment course may be unnecessary unless new TB exposure occurs.
Table: Comparison of TB Screening Periods and Outcomes
| Period | Screening Strategy | LTBI Diagnosis (%) | Preventive Therapy Rate | Incident Active TB (%) |
|——–|—————————–|——————|————————|———————–|
| 1 | Two-step TST | 40.8 | High | – |
| 2 | Two-step TST + QFT Gold | Decreased | Decreased | – |
| 3 | Single-step TST + QFT Gold | Further decreased| Further decreased | – |
| 4 | QFT Gold alone | 14.8 | Lowest | 0.8 |
Expert Commentary
This two-decade, real-world experience from a specialized TB clinic in a low-prevalence country highlights the effectiveness of QFT Gold as a stand-alone screening test for TB before initiating biologic therapy. The optimized strategy reduced false-positive diagnoses leading to unwarranted preventive therapy without compromising patient safety.
Current guidelines, such as those from the American Thoracic Society and the European Respiratory Society, support IGRA-based screening in BCG-vaccinated populations due to superior specificity compared to TST. This study adds robust long-term outcome data reinforcing this approach.
Limitations include its retrospective design and setting within a low-prevalence country, which may limit generalizability to high TB burden contexts where dual testing or more frequent retesting might still be warranted.
Mechanistically, QFT Gold detects interferon-gamma release from T cells sensitized to specific Mycobacterium tuberculosis antigens absent in BCG and most nontuberculous mycobacteria, improving specificity over TST.
Conclusion
This comprehensive cohort study validates that QFT Gold alone is sufficient for pre-biologic TB screening in low-prevalence settings, effectively reducing unnecessary treatment without increasing active TB risk. Routine periodic retesting during biologic therapy appears unnecessary unless new TB exposure occurs.
These findings can streamline clinical workflows, minimize patient burden and adverse effects from preventive therapy, and inform guideline updates. Future studies are needed in diverse epidemiologic settings to further define optimal screening algorithms.
References
Pérez-Recio S, Grijota-Camino MD, Guardiola J, et al; Prevention of Tuberculosis Associated with Biologic Therapies Study Group. Prevention of Tuberculosis in Patients Treated With Biological Therapies: Twenty Years’ Experience in a Specialised Tuberculosis Clinic in a Low-prevalence Country. Clin Infect Dis. 2025 Sep 5:ciaf491. doi: 10.1093/cid/ciaf491. Epub ahead of print. PMID: 40911528.
American Thoracic Society, CDC, and Infectious Diseases Society of America. Latent Tuberculosis Infection: A Guide for Primary Health Care Providers. Am J Respir Crit Care Med. 2020;201(8):e70-e79.
Pai M, Behr MA, Dowdy D, et al. Tuberculosis. Nat Rev Dis Primers. 2016;2:16076. doi:10.1038/nrdp.2016.76