SAT0366 Serum uric acid increases after abrogation of systemic inflammation by tnf inhibition
Authors: L. Petru, H. Hulejova, A. Mahajan, M. Herrmann, J. Zavada
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In patients with gout, the serum uric acid (SUA) is usually lower during acute gouty attacks than during intercritical periods. It has been suggested that systemic inflammatory response can cause this phenomenon. <h3>Objectives</h3> We aimed to investigate whether SUA levels are associated with levels of pro-inflammatory cytokines in patients with systemic autoimmune rheumatic diseases: rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) and whether the initiation of a therapy with TNF inhibitors (TNFi) would change levels of SUA. <h3>Methods</h3> A cohort of 128 patients with clinically active chronic inflammatory rheumatic disease (44 with RA, 45 with AS, 23 with PsA, 16 with JIA) and CRP≥10 mg/L was recruited in the Institute of Rheumatology, Prague. SUA, CRP, creatinine, MCP-1, IFN-α2, IFN-γ, Il-1β, IL-6, IL-8, IL-10, IL-12, IL-17a, IL-18, IL-23, IL-33 and TNF-α were measured in serum before and after 3 months of treatment with TNFi. We employed bead-based immunoassays to quantify the cytokines and retrieved demographic data, BMI and co-medications. We present the data as mean ±standard deviation or mean and 95% Cl. <h3>Results</h3> SUA was significantly lower before initiation of TNFi (288.5±78.7 μmol/l) than after 3 months of treatment (307.7±81.7 μmol/l, p=0.0002). The level of CRP (38.9±30.3 <i>vs</i> 5.0±7.6 mg/L, p&lt;0.0001), IL-6 (172.8±339.0 <i>vs</i> 24.2±32.5 pg/ml, p&lt;0.0001) and MCP-1 (1062±554.7 <i>vs</i> 959.2±508.9 pg/ml, p=0.015) significantly decreased during treatment. When we grouped our patients according to sex and diagnosis, the SUA levels significantly increased in the male patients (311.4±79.5 <i>vs</i> 343.9±74.3 μmol/l, p&lt;0.0001), patients with AS (298.4±70.0 <i>vs</i> 326.4±73.1 μmol/l, p=0.0009) and with PsA (302.6±75.3 <i>vs</i> 334.6±74.3 μmol/l, p=0.033), but not in patients with RA or JIA. There was no correlation between the magnitude of the change of SUA, CRP and pro-inflammatory cytokines or the reported use of NSAIDs. However, when we classified our cohort according to increase or decrease of SUA after initiation of TNFi, we observed statistically significant differences in the changes of IL-1β (1.5,–10.8 to 13.9, <i>vs</i> 29.4, 5.4 to 53.1 pg/ml, p=0.023), IL-23 (0.7,–40.0 to 41.3 <i>vs</i> 102.0, 5.5 to 198.6 pg/ml, p=0.023), IL-33 (−1.2,–26.7 to 24.3 <i>vs</i> 48.8, 3.8 to 93.9 pg/ml, p=0.039) and TNF-α (−0.8,–6.1 to 4.5 <i>vs</i> 10.5, −0.4 to 21.32 pg/ml, p=0.037) between these two groups. <h3>Conclusions</h3> We have shown that abrogation of systemic inflammation by TNFis results in an increase in the levels of SUA within 3 months, especially in male patients with AS or PSA. Our results support the hypothesis that systemic inflammation is associated with a decrease in SUA concentrations. The mechanism remains elusive. However, IL-1β, IL-23, IL-33 and TNF-α are candidate players. The difference between the male and female patients argue for a role of the sex hormones. We cannot exclude the possibility that an underreported differential in the use of NSAIDs, known for their uricosuric effect, may have partly biassed our observations. <h3>Acknowledgements</h3> This work was supported by the Charles University research grant GA UK No.940517 and by the project (Ministry of Health, Czech Republic) for consensual development of research organisation 0 23 728. LP is a recipient of an ARTICULUM Fellowship. <h3>Disclosure of Interest</h3> None declared