AB0124 FEBUXOSTAT MONOTHERAPY IN GOUT: BEYOND URATE-LOWERING EFFICACY – UNVEILING ANTI-INFLAMMATORY POTENTIAL THROUGH CYTOKINE AND COX-2 MODULATION
Authors: K. Kraev, B. Hristov, P. Uchikov, M. Kraeva, Y. Basheva-Kraeva, S. Popova-Belova, M. Geneva-Popova
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Gout, characterized by elevated uric acid levels and associated with increased cytokine production, necessitates effective management strategies. This study aimed to assess the impact of febuxostat monotherapy on inflammatory markers, including interleukin-1 (IL-1), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2), in gout patients, comparing them to a healthy control group. <h3>Objectives:</h3> This study aimed to assess the dual functionality of febuxostat in gout management. Objectives included evaluating its effectiveness in lowering uric acid levels, investigating its anti-inflammatory potential by analyzing cytokine (IL-1, IL-6) and COX-2 modulation, comparing these effects with healthy controls, and assessing long-term implications on clinical symptoms and recurrence rates. The study provides insights into febuxostat's broader role in gout treatment, beyond its traditional urate-lowering capacity. <h3>Methods:</h3> Sixty gout patients undergoing febuxostat monotherapy and twenty healthy controls were enrolled. Serum levels of C-reactive protein (CRP), uric acid, IL-1, IL-6, and COX-2 were measured at baseline (0 months), 3 months, and 6 months using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for within-group comparisons and independent t-tests or Mann-Whitney U tests for between-group comparisons. Clinical symptoms and gout recurrence rates were also monitored. <h3>Results:</h3> Febuxostat-treated patients exhibited a significant reduction in serum IL-1, IL-6, and COX-2 levels at 3 and 6 months, paralleled by decreased symptoms and lower recurrence rates. These anti-inflammatory effects were clinically significant when compared to healthy controls. Uric acid levels also showed sustained decreases over the study period. <h3>Conclusion:</h3> In conclusion, febuxostat monotherapy not only effectively lowered uric acid levels but also demonstrated significant anti-inflammatory effects, as evidenced by reduced cytokine and COX-2 levels. This dual functionality positions febuxostat as a promising therapeutic option for gout, addressing both hyperuricemia and the underlying inflammatory processes. The study suggests that febuxostat may serve not only as a urate-lowering agent but also as a substance with broader anti-inflammatory impacts. Further research is needed to elucidate the precise mechanisms and long-term implications of febuxostat's anti-inflammatory effects, reinforcing its integral role in comprehensive gout management. <h3>REFERENCES:</h3> [1] Hao, G., Duan, W., Sun, J., Liu, J., &amp; Peng, B. (2019). Effects of febuxostat on serum cytokines IL-1, IL-4, IL-6, IL-8, TNF-α and COX-2. <i>Experimental and therapeutic medicine</i>, <i>17</i>(1), 812–816. [2] Collison J. Crystal arthritis: Febuxostat reduces synovitis in early gout. <i>Nat Rev Rheumatol.</i> 2017;13:694. doi: 10.1038/nrrheum.2017.175. [3] Dalbeth N, Saag KG, Palmer WE, Choi HK, Hunt B, MacDonald PA, Thienel U, Gunawardhana L. Effects of febuxostat in early gout: A randomized, double-blind, placebo-controlled study. <i>Arthritis Rheumatol.</i> 2017;69:2386–2395. doi: 10.1002/art.40233. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>