Dynamics and clinical determinants of QuantiFERON-TB gold status changes in patients with inflammatory arthritis receiving TNF-α inhibitors
Zeynel Abidin Akar, Dilan Yıldırım, Zeynep Işık Sula, Mehmet Çiftçi, Ömer Karakoyun, Kadir Kaya, Mehmet KarakoçBackground
Screening and longitudinal monitoring for latent tuberculosis infection (LTBI) using interferon-gamma release assays (IGRAs), such as QuantiFERON-TB Gold (QFT), are mandatory during tumor necrosis factor-alpha (TNF-α) inhibitor therapy. However, the long-term dynamics of serial QFT testing in real-world clinical cohorts—particularly in settings with intermediate tuberculosis burden—remain poorly characterized. This study aimed to investigate the frequency, clinical predictors, and temporal patterns of longitudinal QFT status changes (seroconversion and reversion) in patients with inflammatory arthritis receiving anti-TNF-α therapy.
Objectives
To evaluate the frequency, temporal distribution, and clinical predictors of QuantiFERON-TB Gold (QFT) seroconversion and reversion in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) treated with TNF-α inhibitors.
Design
Retrospective longitudinal cohort study.
Methods
Medical records of 337 consecutive patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) receiving TNF-α inhibitors at a tertiary referral center were retrospectively analyzed. Clinical characteristics, baseline and serial QFT results, and cumulative biologic exposure metrics were extracted. Serial QFT testing was performed as part of routine annual clinical monitoring in accordance with institutional follow-up protocols in an intermediate tuberculosis-burden setting. Kaplan–Meier methods were used descriptively to evaluate time-to-event profiles. Independent demographic and pharmacological predictors of QFT transitions were determined using univariable and multivariable logistic regression analyses.
Results
At baseline, 250 patients (74.2%) were QFT-negative and 87 (25.8%) were QFT-positive. During follow-up, seroconversion occurred in 18 initially negative patients (7.2%), with no statistically significant difference between RA and AS subgroups (7.7% vs. 5.5%, p = 0.702). Multivariable regression identified younger age as the sole independent predictor of seroconversion (adjusted odds ratio [aOR] 0.866, 95% confidence interval [CI] 0.785–0.956; p = 0.004). Conversely, QFT reversion occurred in 10 initially positive patients (11.5%), with comparable rates between RA and AS cohorts (11.8% vs. 10.5%, p = 1.000). Reversion was independently predicted by older age (aOR 1.115, 95% CI 1.036–1.201; p = 0.004) and shorter disease duration (aOR 0.994, 95% CI 0.990–0.998; p = 0.003). Kaplan–Meier analysis demonstrated that seroconversion events clustered early (median 13.0 months), whereas reversions occurred after prolonged biologic exposure (median 39.5 months). Accordingly, cumulative anti-TNF-α exposure was significantly longer in the reversion cohort than in the seroconversion cohort (median 48.0 vs. 12.0 months; p = 0.008). Following seroconversion, all patients underwent clinical evaluation, including symptom assessment and radiological screening, and no cases of active tuberculosis were identified.
Conclusion
Long-term QFT responses exhibit distinct, non-random dynamic variations during TNF-α inhibitor therapy. Younger age is associated with early seroconversion, whereas older age combined with shorter disease duration is associated with reversion, independent of the underlying diagnostic category (RA vs. AS). These real-world findings highlight the need for cautious interpretation of serial IGRA variability in intermediate tuberculosis-burden settings and emphasize that longitudinal monitoring should incorporate patient age and treatment duration to support contextual clinical decision-making regarding latent tuberculosis evaluation.