Mycobacterial Interferon-γ Release Variations During Longterm Treatment with Tumor Necrosis Factor Blockers: Lack of Correlation with Clinical Outcome

Objective. To assess the performance of serial QuantiFeron-TB Gold In-Tube (QFT-GIT) tests in patients with rheumatic diseases during longterm systemic treatment with biologic therapy, evaluating conversions and reversions in relation to the clinical outcome. Methods. We conducted a prospective study on patients awaiting biologic agents. At baseline, they had chest radiographs, QFT-GIT tests, and tuberculin skin tests (TST); QFT-GIT was repeated at 3, 6, 12, and 18 months after onset of biologic therapy. In patients with no evidence of latent tuberculosis infection (LTBI) at baseline, TST was repeated at 12 months of biologic treatment. Results. Among patients (n = 102; women 65.7%; median age 47 yrs, range 20-82), 14 (13.7%) were considered as having LTBI because of a minimum of 1 abnormal screening test. The agreement between QFT-GIT and TST was 88% (kappa = 0.14). During biologic treatment, both patients with (n = 14) and those without (n = 88) evidence of LTBI at baseline showed conversions and reversions in QFT-GIT results at different timepoints. These fluctuations were not paralleled by significant clinical changes. The TST repeated at 12 months in patients with no evidence of LTBI at baseline continued to be negative. The median baseline interferon-gamma (IFN-gamma) concentration was not significantly different from that observed at each subsequent timepoint. Conclusion. Dynamic changes occur with serial lFN-gamma release assay testing in patients treated with biologic therapy that do not correlate with clinical outcome. A careful and integrated evaluation of the patient, including clinical information, should guide the treatment decision. This study was underpowered for definite conclusions and further studies are needed to determine the significance of these findings. (First Release Dec 1 2012; J Rheumatol 2013;40:157-65; doi:10.3899/jrheum.120688)