Objective. To determine the efficacy and safety of increasing the allopurinol dose above the proposed creatinine clearance-based dose in patients with gout.Methods. Patients with gout who had been receiving a stable dose of allopurinol for >1 month were recruited. The dose of allopurinol was increased to obtain the target serum urate level of <0.36 mmoles/ liter (<6 mg/dl). Patients were seen monthly until the serum urate concentration was <0.36 mmoles/liter for 3 consecutive months and then were seen every 3 months for at least 12 months. Data were analyzed using the dosage of allopurinol (mg/day) greater than the recommended dosage, as defined by the Hande criteria.Results. Ninety patients were enrolled. The mean age of the patients was 58.7 years (range 27-83 years), 87.9% were male, and 81.9% were of European ancestry. Forty-five patients had a serum urate concentration of >0.36 mmoles/liter, and the dose of allopurinol was increased in these patients. Rashes developed in 3 patients, and either allopurinol was discontinued or dose escalation was ceased in these patients. Seven patients were lost to followup or developed intervening medical problems that precluded dose escalation. In 31 (88.8%) of 35 patients who completed the study, the serum urate level was <0.36 mmoles/liter at 12 months. Two of the 5 patients who had a serum urate level >0.36 mmoles/liter had undetectable levels of plasma oxypurinol, indicating noncompliance with allopurinol treatment. A significant reduction in the serum urate concentration was observed for all allopurinol doses above the recommended dose. Eighteen of 45 patients were receiving furosemide; those receiving furosemide were just as likely as those not receiving furosemide to achieve a serum urate concentration of <0.36 mmoles/ liter (72% versus 88.5%; P ‫؍‬ 0.24). Patients receiving furosemide required a higher dose of allopurinol to achieve the target serum urate concentration. No serious adverse events were observed.Conclusion. Increasing the dose of allopurinol above the proposed creatinine clearance-based dose led to a significant reduction in the serum urate concentration. Approximately 89% of patients achieved a serum urate concentration of <0.36 mmoles/liter. In this cohort, toxicity was not increased in patients receiving higher doses of allopurinol, including those with renal impairment.Gout is the most common form of arthritis in men older than age 40 years, and the incidence of gout is increasing (1). Gout is a complex inflammatory response to the presence of monosodium urate (MSU) crystals in joints. MSU crystals can form when serum urate supersaturation concentrations are reached (ϳ0.4 mmoles/liter [6.7 mg/dl] at 37°C). Gout typically presents as self-limiting episodes of acute inflammatory arthritis. With time, untreated hyperuricemia and recurrent attacks of gout lead to bone and joint damage, deposition of MSU as tophi, and ultimately disability. Gout is also associated with increased mortality, especially that related to cardiovascular disease (2-4).Lowerin...

Objective. There is evidence supporting a therapeutic range for methotrexate polyglutamate ( Conclusion. There is wide interpatient variability of RBC MTXGlu 1-5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu 1-5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered.

These data suggest that increased CCL3L1 expression may enhance inflammatory responses and increase the chance of autoimmune disease. Genetic interaction data were consistent with a biologically plausible model; CCR5Delta32 protects against RA and T1D by blocking signalling through the CCR5 pathway, mitigating the pro-inflammatory effects of excess CCL3L1.

Objective. Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) in the management of rheumatoid arthritis (RA). MTX is transported into cells

The prevalence of WG and MPA in Canterbury is the highest reported to date. Restricting the case definition of WG to the ACR classification criteria we found a prevalence equivalent to that described in northern Norway. The clinical severity and serological characteristics were similar to descriptions in other WG and MPA patient cohorts. Studies of disease prevalence in other Southern Hemisphere centres will determine if the observed north-south negative disease gradient in the Northern Hemisphere is reciprocated.

A north-south gradient in the rate of patient discharges given a diagnostic code of M313 (WG, necrotizing respiratory granulomatosis) was present in NZ. This finding supports the hypothesis that there is a latitude-dependent risk factor(s) for WG possibly common to both global hemispheres.

Objective. There are limited data suggesting that methotrexate polyglutamate (MTXGlu) concentrations can guide MTX dosing in patients with rheumatoid arthritis (RA). The aim of this study was to define a therapeutic range of red blood cell (RBC) MTXGlu n concentrations (where n refers to the number of glutamate groups), including threshold values for efficacy and adverse effects in patients receiving long-term oral MTX treatment.Methods. A cross-sectional study of 192 patients receiving oral MTX was undertaken. Disease activity was assessed by the swollen and tender joint counts, the C-reactive protein level, and the Disease Activity Score in 28 joints (DAS28). High disease activity was defined as a DAS28 of >3.2. A standardized questionnaire regarding common MTX adverse effects was completed.Results. The MTX dosage was significantly higher in patients in whom the swollen joint count and DAS28 were higher. The MTXGlu 4 , MTXGlu 5 , MTXGlu 3-5 , and MTXGlu 1-5 concentrations were significantly higher in patients with high disease activity. After correction for age, the estimated glomerular filtration rate, and the MTX dosage, the association remained significant for MTXGlu 5 . RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlu n concentration and adverse effects.Conclusion. In contrast to other studies, the results of the present study did not show a relationship between the MTXGlu n concentration and reduced disease activity in patients with RA who were receiving long-term MTX therapy. However, disease activity was influenced by the RBC folate level, which may be a more important factor than MTXGlu n concentrations for disease control. In accordance with the findings of previous studies, we were unable to show a relationship between MTXGlu n concentrations and adverse effects. Prospective studies will be important to determine whether there is a role for measuring MTXGlu n concentrations in patients receiving long-term treatment with MTX.

The treatment of gout requires a lowering of serum urate (SU) levels, and allopurinol is the drug that is most commonly used for this purpose. The objectives of this study were to define the relationships between allopurinol dose on the one hand and plasma oxypurinol, renal function, and SU levels on the other and to determine the minimum plasma oxypurinol concentration that would result in a target level of <6 mg/dl (0.36 mmol/l) of SU. For this purpose, 82 patients who had been receiving allopurinol for at least 1 month were recruited. Patients with SU <6 mg/dl were followed up quarterly for 12 months. In patients with SU ≥6 mg/dl, the dose of allopurinol was increased to bring the level of SU to <6 mg/dl. These patients were followed up once a month until the SU level remained at <6 mg/dl for 3 consecutive months; thereafter they were seen quarterly. SU, creatinine, and plasma oxypurinol were measured 6-9 hours after administration of the allopurinol dose. There were significant inverse correlations between creatinine clearance (CrCl) and plasma oxypurinol (P = 0.002), between allopurinol dose and SU (P < 0.0001) and between plasma oxypurinol and SU (P < 0.0001). Using receiver operating characteristic analysis, the target SU of <6 mg/dl was achieved in 75% of serum samples with plasma oxypurinol levels of >100 µmol/l (15.2 mg/l). Increasing the allopurinol dose resulted in increased plasma oxypurinol and reduced SU concentrations. Plasma oxypurinol concentrations >100 µmol/l were required to achieve SU <6 mg/dl.