Rheumatology International

, Volume 39, Issue 10, pp 1749–1757 | Cite as

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

  • Lenka Hasikova
  • Marketa Pavlikova
  • Hana Hulejova
  • Petr Kozlik
  • Kveta Kalikova
  • Aparna Mahajan
  • Martin Herrmann
  • Blanka Stiburkova
  • Jakub ZavadaEmail author
Observational Research


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.


Uric acid Inflammation Rheumatic diseases Cytokines Oxidative stress 



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.

Author contributions

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.


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.

Compliance with ethical standards

Conflict of interest

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

Ethical approval

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of RheumatologyPrague 2Czech Republic
  2. 2.Department of Rheumatology, First Faculty of MedicineCharles UniversityPragueCzech Republic
  3. 3.Department of Probability and Mathematical Statistics, Faculty of Mathematics and PhysicsCharles UniversityPragueCzech Republic
  4. 4.Department of Analytical Chemistry, Faculty of ScienceCharles UniversityPragueCzech Republic
  5. 5.Department of Physical and Macromolecular Chemistry, Faculty of ScienceCharles UniversityPragueCzech Republic
  6. 6.Department of Internal Medicine 3, Rheumatology and ImmunologyFriedrich-Alexander University of Erlangen-NürnbergErlangenGermany
  7. 7.Department of Pediatrics and Adolescent Medicine, First Faculty of MedicineCharles University and General University Hospital in PraguePragueCzech Republic

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