AB0269 ARE INTERFERON-GAMMA RELEASE ASSAYS RELIABLE TO DETECT TUBERCULOSIS INFECTION IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH JANUS KINASE INHIBITORS?
Authors: C. Castellani, E. Molteni, A. Altobelli, C. Garufi, S. Mancuso, F. R. Spinelli, F. Ceccarelli, F. Conti, R. Scrivo
Journal: Annals of the Rheumatic Diseases (2021)

Background: The therapeutic armamentarium for patients with rheumatoid arthritis (RA) has recently been enriched with the family of Janus kinase (JAK) inhibitors. Because the risk of reactivation of latent tuberculosis infection (LTBI) following the use of these drugs seems to be similar to that seen with anti-TNF agents, screening for LTBI is recommended in patients with RA before starting treatment with JAK inhibitors. Interferon(IFN)-gamma release assays (IGRAs) are increasingly used for this purpose. However, JAK inhibitors tend to decrease the levels of IFNs, questioning the reliability of IGRAs during treatment with this novel class of drugs. Objectives: To compare the performance of the QuantiFERON-TB Gold Plus (QFT-Plus) test with that of QuantiFERON-TB Gold In-tube (QFT-GIT) assay in RA patients before and during treatment with JAK inhibitors. Methods: A longitudinal, prospective study has been performed in RA patients (ACR/EULAR 2010 criteria) candidates for tofacitinib or baricitinib treatment. All patients underwent QFT-Plus and QFT-GIT at baseline (T0), and after 3 (T3) and 9/12 months (T9/12) of treatment with JAK inhibitors. The agreement of the two tests was calculated at all timepoints. The agreement between IGRAs and tuberculin skin test (TST) or chest radiography at baseline was also determined. Lastly, the variability of QTF-Plus results was assessed during follow-up. Results: Twenty-nine RA patients (F/M 23/6; median age/IQR 63/15.5 years; median disease duration/IQR 174/216 months) were enrolled: among them, 22 were to start baricitinib (75.9%) and 7 tofacitinib (24.1%). A perfect agreement was found between QFT-Plus and QFT-GIT at all times of observation ( κ= 1). At baseline, no agreement was recorded between IGRAs and TST ( κ= -0.08) and between TST and chest radiography ( κ= -0.07), while a low agreement was found between QFT-Plus and chest radiography ( κ= 0.17). A variation of 33.3% in the results of the QFT-Plus test was recorded at T3 compared to T0, of 29.4% at T9/12 compared to T0, and of 11.8% at T9/12 compared to T3. The median levels of IFN-γ produced by lymphocytes in response to the mitogen of QFT-Plus decreased after 3 months of treatment (1.59/4.72 IU/ml vs 3.08/7.68 IU/ml at baseline), followed by an increase after 9/12 months (2.25/4.61 IU/ml), but these differences were not significant. No significant change in the median number of circulating lymphocytes such as to explain the variation of the QFT-Plus results after 3 months of JAK inhibitor therapy was documented (1815/690/mm 3 vs 2140/750/mm 3 at baseline). At baseline, both QFT-Plus and QFT-GIT showed positive results in 5 patients (17.2%), negative in 19 (65.5%), and indeterminate in 5 (17.2%). Glucocorticoids intake was associated with a higher probability of negative or indeterminate result of IGRAs at baseline ( p &lt;0.0001). Conclusion: Our data show that a response to IGRAs is detectable in the course of treatment with JAK inhibitors. However, similarly to what has been observed during treatment with TNF antagonists, the results of QFT-GIT and QFT-Plus show some variability when longitudinally repeated. These fluctuations occur in the absence of correlation with clinical outcome, thus challenging their interpretation. Since we do not have a sufficiently sensitive test capable of detecting TB infection, an integrated evaluation of risk factors, clinical manifestations and multiple diagnostic tests should be considered for a proper evaluation of the risk of TB infection in immunosuppressed patients. Disclosure of Interests: None declared