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Serum uric acid increases in patients with systemic autoimmune rheumatic diseases after 3 months of treatment with TNF inhibitors

Abstract

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. The objective is to determine whether therapy with TNF inhibitors (TNFis) affects SUA levels in patients with systemic autoimmune rheumatic diseases (SARDs) and whether SUA changes correlate with pro-inflammatory cytokines or with the oxidative stress marker allantoin. In this study, 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, TNF-α, and allantoin levels were measured prior to and after 3 months of TNFis treatment in patients with SARDs. The values obtained in the biochemical assays were then tested for associations with the patients’ demographic and disease-related data. A total of 128 patients (rheumatoid arthritis, n = 44; ankylosing spondylitis, n = 45; psoriatic arthritis, n = 23; and adults with juvenile idiopathic arthritis, n = 16) participated in this study. Among the entire patient population, SUA levels significantly increased 3 months after starting treatment with TNFis (279.5 [84.0] vs. 299.0 [102.0] μmol/l, p < 0.0001), while the levels of CRP, IL-6, IL-8, and MCP-1 significantly decreased. Male sex was the most powerful baseline predictor of ΔSUA in univariate and multivariate models. None of the measured laboratory-based parameters had statistically significant effects on the magnitude of ΔSUA. 3 months of anti-TNF therapy increased the levels of SUA in patients with SARDs, but neither the measured pro-inflammatory cytokines nor the oxidation to allantoin appeared responsible for this effect.

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Acknowledgements

We would like to thank Dr. Laszlo Wenchich and the members of the Department of Clinical Biochemistry and Hematology (Institute of Rheumatology) for their kind assistance with the biochemical measurements.

Funding

This work was supported by the Charles University Research Grant GA UK no. 940517, the Ministry of Health of the Czech Republic (Institute of Rheumatology—Conceptual Development of Research Organization, 00023728), and the Czech Science Foundation, Grant no. 19-18005Y. LH was a recipient of the ARTICULUM Fellowship.

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All authors were involved in drafting the manuscript or revising it critically for content. LH planned and performed most of the measurements, conducted data analysis, and wrote the manuscript. MP conducted statistical data analysis and prepared the figures. HH and AM helped with measurements of cytokines and with analyzing data. PK and KK carried out mass spectrometric measurements. MH and BS provided scientific input and interpretation of data. JZ designed the project, supervised its conduct, and helped to write the manuscript. The final manuscript has been seen and approved by all authors.

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Correspondence to Jakub Zavada.

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All authors declare that there is no conflict of interest regarding the publication of this article.

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All procedures in this study were in accordance with the ethical standards of the institutional and national research committee (Czech Multicentre Research Ethics Committee, no. 201611 S300 and Institutional Ethics Committee of Institute of Rheumatology, Prague, Czech Republic, no. 10113/2016) and with the 1964 Helsinki declaration and its later amendments.

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Hasikova, L., Pavlikova, M., Hulejova, H. et al. Serum uric acid increases in patients with systemic autoimmune rheumatic diseases after 3 months of treatment with TNF inhibitors. Rheumatol Int 39, 1749–1757 (2019). https://doi.org/10.1007/s00296-019-04394-6

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  • DOI: https://doi.org/10.1007/s00296-019-04394-6

Keywords

  • Uric acid
  • Inflammation
  • Rheumatic diseases
  • Cytokines
  • Oxidative stress