Background Methotrexate is the cornerstone DMARD in the treatment of rheumatoid arthritis. The exact mechanism of action is elusive, but it may be related to increase in adenosine levels. Methotrexate may be increasing the adenosine levels by blocking its natural conversion to uric acid.
Objectives The purpose of this study was to determine if methotrexate therapy lowers serum uric acid levels in patients with early rheumatoid arthritis compared to controls who were not treated with methotrexate.
Methods Data were obtained from CATCH (Canadian Early Arthritis Cohort), a prospective early RA cohort. This was a nested case control study. All patients with methotrexate use and a diagnosis of early rheumatoid arthritis (ERA) were included if they had a serum uric acid performed before starting methotrexate and again while taking methotrexate. Patients with ERA who did not receive any methotrexate were used as controls if they had serial uric acid measurements.
Results Forty-nine ERA patients, out of 2524, in the CATCH database on methotrexate therapy with serial serum uric acid measurements were identified. In this group, the mean pre-methotrexate uric acid level was 300 μmol/L with a mean post-methotrexate uric acid level of 273 μmol/L (p 0.035). The control group of ERA patients not taking methotrexate during this time had a mean baseline uric acid level of 280 μmol/L and a follow-up level of 282 μmol/L (p 0.448). The mean change in uric acid levels in serum in patients treated with methotrexate was -26.8 μmol/L, while the control group had a mean change of 2.3 μmol/L (p=0.042). Patients who experienced a decrease in serum uric acid levels in relation to their methotrexate treatment had a DAS28 score of 2.37 at 18 months, while the control group had a DAS28 of 3.26 (p=0.042). Patients treated with methotrexate who experienced a decrease in uric acid levels had a SJC28 of 0.89 at 18 months, while patients on methotrexate who did not experience a decrease in uric acid levels had a SJC28 of 4.47 (p=0.035).
Conclusions Methotrexate is fundamental in the treatment of ERA and it is thought to work through increase in adenosine levels. By this postulated mechanism of action, uric acid levels were shown to be decreased in a clinical setting for patients taking methotrexate for ERA. This could be an indirect mechanism whereby methotrexate improves cardiovascular risk
Disclosure of Interest None declared
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