Background: Hyperuricemia associated with rheumatoid arthritis (RA) has been reported to be a risk factor for cardiovascular disease. It has been reported that uric acid (UA) levels decrease with the use of leflunomide and increase with tumor necrosis factor (TNF) inhibitor therapy. However, the effects of long-term biological disease-modifying antirheumatic drugs (bDMARDs) therapy and the effects of non-TNF inhibitor biologic therapy on UA levels have not been reported.

Objectives: We aimed to investigate the changes in UA levels during the use of TNF inhibitors and non-TNF inhibitors therapy.

Methods: Patients with RA treated with bDMARDs from 2008 to 2018 were studied based on the All Showa University of RA (ASHURA) database. The association between uric acid level reduction and treatment was evaluated. Of 629 patients treated with the bDMARDs, 256 patients with available uric acid levels medical records were included. The following background factors were investigated: age; sex; type of bDMARDs; dosage of methotrexate and prednisolone; usage of conventional synthetic DMARDs, dyslipidemia drugs and nonsteroidal anti-inflammatory drugs; body mass index; smoking history; HbA1c; presence or absence of hypertension and dyslipidemia; and serum creatinine, C-reactive protein, and matrix metalloproteinase-3 levels. We also used the simplified disease activity index (SDAI) to evaluate RA disease activity. The analysis was performed in two groups, TNF inhibitor-treated group (148 patients) and non-TNF inhibitor-treated group (108 patients, tocilizumab and abatacept).　The primary endpoint was UA levels before, and after 6 months and 1 year, which was determined using the repeated-measures analysis of variance (ANOVA) and secondary endpoint was proportion of patients with hyperuricemia (uric acid level of 7.0 or higher was defined), determined using spearman’s correlation coefficient by rank test.

Results: In TNF inhibitor-treated group, the UA levels were not increased from 4.9 ± 1.4 (mg/dl) to 4.9 ± 1.4 and 5.1 ± 1.7 before treatment and after 6 months and 1 year, respectively (p=0.50). The number of patients with hyperuricemia increased from 7 to 12 and 16 (p=0.026). In non- TNF inhibitor-treated group, the UA levels were not increased from 5.2 ± 1.4 (mg/dl) to 5.2 ± 1.4 and 5.3 ± 1.4 (p=0.78). The number of patients with hyperuricemia increased from 8 to 16 and 12 (p=0.193). There was a difference in the type of drug, but no difference in the duration of administration by repeated-measures ANOVA.

Conclusion: Our study suggests that TNF inhibitor therapy may affect increased percentage of patients with hyperuricemia. On the other hand, non-TNF inhibitor therapy may not affect increased percentage of patients with hyperuricemia and bDMARD treatment has a mild effect on UA levels in patients with RA.

Acknowledgements: Nobuyuki Yajima, Takeo Isozaki, Kuninobu Wakabayashi, Sakiko Isojima, Ryo Takahashi, Hidekazu Furuya, Takahiro Tokunaga, Sho Ishii, Shinya Seki, Mayu Saito, Shinichiro Nishimi, Airi Nishimi, Yuzo Ikari, Mika Hatano, Tomoki Hayashi, Masahiro Hosonuma, Yoichi Toyoshima and Katsunori Inagaki, Kosuke Sakurai

Disclosure of Interests: None declared