Reduction in Serum Uric Acid may be Related to Methotrexate Efficacy in Early Rheumatoid Arthritis: Data from the Canadian Early Arthritis Cohort (CATCH)

Abstract

OBJECTIVESThe mechanism of action of methotrexate in rheumatoid arthritis (RA) is complex. It may increase adenosine levels by blocking its conversion to uric acid (UA). This study was done to determine if methotrexate lowers UA in early RA (ERA).METHODSData were obtained from Canadian Early Arthritis Cohort, an incident ERA cohort. All ERA patients with serial UA measurements were included, comparing those with methotrexate use vs. no methotrexate exposure (controls). Analyses were exploratory. Patients with concomitant gout or taking UA-lowering therapies were excluded.RESULTSIn total, 49 of the 2,524 ERA patients were identified with data available for both pre-methotrexate UA levels and post-methotrexate UA levels (300 µmol/L and 273 µmol/L, respectively; P = 0.035). The control group not taking methotrexate had a mean baseline UA level of 280 µmol/L and a follow-up level of 282 µmol/L (P = 0.448); mean change in UA with methotrexate was −26.8 µmol/L vs. 2.3 µmol/L in the no methotrexate group (P = 0.042). Methotrexate users with a decrease in UA had a disease activity score of 2.37 for 28 joints when compared with the controls (3.26) at 18 months (P = 0.042). Methotrexate users with decreased UA had a lower swollen joint count (SJC) of 0.9 at 18 months, whereas methotrexate users without lowering of UA had an SJC of 4.5 (P = 0.035). Other analyses were not significant.CONCLUSIONSMethotrexate response is associated with lowering of serum UA in ERA compared to nonusers. This may be due to changes in adenosine levels. Methotrexate response is associated with lower UA and fewer swollen joints compared to nonresponders.

The effect of subcutaneous methotrexate on markers of metabolic syndrome in psoriatic patients – preliminary report

“…This may be due to changes in adenosine levels, which is a key mechanism of anti-inflammatory effects. Increased adenosine levels, theoretically, result from decreased xanthine and uric acid synthesis [ 37 ]. It is also a strong proatherogenic factor, especially in a sustained concentration above 4 mg/dl [ 38 ].…”

Diet Quality and Its Relationship with Antioxidant Status in Patients with Rheumatoid Arthritis

“…Impaired antioxidant status in the RA group may be related to the loss of antioxidant components due to the neutralisation of radicals produced as a consequence of inflammation in the joints involved, and this may be also caused by an inadequate supply of antioxidant nutrients [ 36 , 37 ]. Depletion of the antioxidant pool in RA may be also a consequence of therapy [ 38 ]. In the studied RA group, an inverse correlation of TAS with disease duration and number of swollen joints was shown.…”

“…A strong relationship between TAS values and the concentration of uric acid levels in healthy subjects, as well as populations with different chronic diseases, has been previously shown in several studies [ 20 , 41 ]. More than half of the RA group were treated with methotrexate, which could affect the level of uric acid and hence deplete the pool of low-molecular-weight antioxidants in serum [ 38 ]. The uric acid determination performed in our study, however, did not reveal significant differences between groups ( p = 0.062).…”

Recognition of gout in rheumatoid arthritis

“…[8] Moreover, MTX and LEF are commonly taken by patients with RA that reduce uric acid levels also. [9,10] A recent study has demonstrated coexistence of RA and gout are not uncommon. [11–13] However, a study by Petsch et al claimed incidence of gout with patients with RA do exist but is lower than the general population.…”

“…Meanwhile, the patient's serum uric acid level was slightly raised. It may be due to: Female patients have estrogen and progesterone which can promote the elimination of uric acid such that it can maintain the normal uric acid levels; as our patient was on MTX and LEF for the treatment of RA, it is possible that MTX can inhibit synthesis of purine and increase the level of adenosine, [9] and LEF can increase the elimination of uric acid by reducing the levels of uric acid through regulation of urate transporter in renal epithelial cells [10] ; and RF is likely to prevent the deposition of uric acid crystals. Hence, for these reasons, the level of uric acid presents to be slightly higher, or even normal.…”