Gout Assessment Questionnaire: Initial results of reliability, validity and responsiveness.

We evaluated the psychometric properties of a new gout-specific patient reported outcomes questionnaire. The Gout Assessment Questionnaire (GAQ) and the SF-36 were administered to 126 subjects in a multicenter Phase II program of febuxostat, an investigational treatment for hyperuricemia (serum uric acid >8.0 mg/dl) in patients with chronic gout. The questionnaire was administered at baseline and 1, 6 and 12 months later. The majority of subjects, mean age 54 years, were male, Caucasian and had experienced a gout flare within the last year. Seven domains were identified, all met criteria for reliability and validity. Cronbach's alpha ranged from 0.78 to 0.97. Pearson correlations between GAQ and SF-36 scales were generally low to moderate, with the highest correlation between Gout Pain and Severity and SF-36 Bodily Pain, r = 0.45. Guyatt's statistic (measure of responsiveness) ranged from 0.24 to 1.00 at 12 months. Minimal clinically important differences ranged from 2 (Gout Concern) to 10 points (Productivity). The GAQ has acceptable psychometric properties. Further research is required to confirm results, which may provide more information to improve the GAQ for use in clinical trials.

Magnetic resonance imaging in the quantitative assessment of gouty tophi.

Measurements of tophus size can be important in monitoring the course of gout therapy, as tophus resolution is proposed as one measure of success of treatment. This multicentre study assessed the intra- and interreader reproducibility of quantitative tophus volume measurements from magnetic resonance images (MRI) in subjects with palpable gouty tophi. Subjects first underwent radiographic imaging of a selected tophus followed by MRI before and at

Febuxostat (TMX-67), a novel, non-purine, selective inhibitor of xanthine oxidase, is safe and decreases serum urate in healthy volunteers.

In order to evaluate the safety, pharmacological properties, and urate-lowering efficacy of febuxostat, a non-purine, selective inhibitor of xanthine oxidase, a Phase 1, 2-week, multiple-dose, placebo-controlled, dose-escalation study was conducted in 154 healthy adults of both sexes. Daily febuxostat doses in the range 10 mg to 120 mg resulted in proportional mean serum urate reductions ranging from 25% to 70% and in proportional increases in maximum febuxostat plasma concentrations and area under plasma concentration versus time curves. Accompanying the hypouricemic effect were increases in serum xanthine concentrations, decreases in urinary uric acid excretion, and increases in urinary xanthine and hypoxanthine excretion, confirming inhibition of xanthine oxidase activity by febuxostat. Hepatic conjugation and oxidative metabolism were the major pathways of elimination of febuxostat from the body, and renal elimination did not appear to play a significant role. Although not uncommon, adverse events were mild and self-limited, and no deaths or serious adverse events were observed. Febuxostat is a safe and potent hypouricemic agent in healthy humans.