Effects of Febuxostat in Early Gout: A Randomized, Double-Blind, Placebo-Controlled Study.

Objective: To assess the effect of treatment with febuxostat versus placebo on joint damage in hyperuricemic subjects with early gout (1 or 2 gout flares).

Methods: In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (increased to 80 mg if the serum UA level was ≥6.

Randomized controlled trial of febuxostat versus allopurinol or placebo in individuals with higher urinary uric acid excretion and calcium stones.

Background And Objectives: Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation. Febuxostat, a xanthine oxidoreductase inhibitor, is effective in lowering serum urate concentration and urinary uric acid excretion in healthy volunteers and people with gout. This work studied whether febuxostat, compared with allopurinol and placebo, would reduce 24-hour urinary uric acid excretion and prevent stone growth or new stone formation.

Preservation of renal function during gout treatment with febuxostat: a quantitative study.

Background: Hyperuricemia can accelerate renal decline associated with aging. Chronic kidney disease is frequently seen in patients with hyperuricemia and gout.

Objectives: Assess the impact of urate-lowering therapy on renal function in subjects with gout who were treated with febuxostat for ≤ 48 months.

The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age.

Background: The incidence of gout rises with increasing age. Management of elderly (≥65 years) gout patients can be challenging due to high rates of comorbidities, such as renal impairment and cardiovascular disease, and concomitant medication use. However, there is little data specifically addressing the efficacy and safety of available urate-lowering therapies (ULT) in the elderly.

African American patients with gout: efficacy and safety of febuxostat vs allopurinol.

Background: African Americans are twice as likely as Caucasians to develop gout, but they are less likely to be treated with urate-lowering therapy (ULT). Furthermore, African Americans typically present with more comorbidities associated with gout, such as hypertension, obesity, and renal impairment. We determined the efficacy and safety of ULT with febuxostat or allopurinol in African American subjects with gout and associated comorbidities and in comparison to Caucasian gout subjects.

Treating hyperuricemia of gout: safety and efficacy of febuxostat and allopurinol in older versus younger subjects.

Despite an increasing incidence of gout in older age patients with multiple metabolic and cardiovascular comorbidities, there are limited data addressing whether currently available urate-lowering therapy is comparably effective and safe in older (≥65 years of age) versus younger (<65 years of age) patients. In this secondary analysis of data from the CONFIRMS trial, we found that among 374 older subjects, urate-lowering therapy with approved doses of febuxostat or commonly prescribed doses of allopurinol was at least comparable to that in 1894 younger subjects and was well tolerated despite high rates of renal impairment and cardiovascular comorbidities in the older subjects.

Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol.

Objective: To compare the characteristics of female versus male gout patients and assess urate-lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout.

Methods: This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level ≥8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function).

Bringing it all together: a novel approach to the development of response criteria for chronic gout clinical trials.

Objective: To review a novel approach for constructing composite response criteria for use in chronic gout clinical trials that implements a method of multicriteria decision-making.

Methods: Preliminary work with paper patient profiles led to a restricted set of core-set domains that were examined using 1000Minds™ by rheumatologists with an interest in gout, and (separately) by OMERACT registrants prior to OMERACT 10. These results and the 1000Minds approach were discussed during OMERACT 10 to help guide next steps in developing composite response criteria.

Serum urate in chronic gout--will it be the first validated soluble biomarker in rheumatology?

Objective: To summarize evidence for and endorsement of serum urate (SU) as having fulfilled the OMERACT filter as a soluble biomarker in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10).

Methods: Data were presented to support the use of SU as a soluble biomarker in chronic gout and specifically the ability to utilize it to predict future patient-reported outcomes.

Results: SU was accepted as having fulfilled the OMERACT filter by 78% of voters.

Tophus measurement as an outcome measure for clinical trials of chronic gout: progress and research priorities.

Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed upon method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to more complex advanced imaging methods. This article summarizes methods of tophus measurement and discusses their properties.

Patient-reported outcomes in chronic gout: a report from OMERACT 10.

Objective: To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10).

Methods: During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.

Febuxostat in gout: serum urate response in uric acid overproducers and underexcretors.

Objective: Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate (sUA) levels in gouty patients who were either overproducers or underexcretors.

Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy: analysis of data from three phase III trials.

Background: Use of urate-lowering therapy (ULT), such as febuxostat or allopurinol, is recommended for the long-term management of hyperuricemia in patients with gout to reduce the incidence of acute flares. Because of the paradoxical relationship between early use of ULT and the increased incidence of gout flares, prophylaxis with either low-dose colchicine or NSAIDs has been recommended, although there have been concerns about the long-term prophylactic use of these agents.

Objectives: The present analysis examined flare rates during the 3 Phase III trials of febuxostat based on mean postbaseline serum urate (sUA) concentrations and duration of prophylaxis.

Renal function in gout: long-term treatment effects of febuxostat.

Background: The association between hyperuricemia, gout, and impaired renal function has long been recognized. Recent data provide evidence for the causal relationship between elevated serum urate (sUA) and renal changes, leading to declines in glomerular filtration rates. In healthy adults, glomerular filtration rate wanes with age.

Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer.

Purpose: Although the murine orthologue of glycoprotein nonmetastatic B (GPNMB), Osteoactivin, promotes breast cancer metastasis in an in vivo mouse model, its importance in human breast cancer is unknown. We have examined the significance of GPNMB expression as a prognostic indicator of recurrence and assessed its potential as a novel therapeutic target in breast cancer.

Experimental Design: The clinical significance of GPNMB expression in breast cancer was addressed by analyzing GPNMB levels in several published gene expression data sets and two independent tissue microarrays derived from human breast tumors.

Progress in measurement instruments for acute and chronic gout studies.

Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the gout workshop, in breakout groups, and at informal meetings of the gout group.

Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout.

Objective: To determine longterm urate-lowering efficacy and clinical benefits and safety of therapy with febuxostat or allopurinol in subjects with gout.

Methods: Subjects (n=1086) in this open-label extension study were assigned to fixed-dose daily urate-lowering treatment (ULT) with febuxostat (80 mg or 120 mg) or allopurinol (300 mg). ULT reassignment was permitted during months 1 to 6 to achieve serum urate (SUA) concentrations between 3.

Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial.

Objective: To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.

Methods: Subjects (n = 1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.

Determinants of the clinical outcomes of gout during the first year of urate-lowering therapy.

Clinical benefit early in urate-lowering treatment of gout is difficult to document. We examined data from 1,832 gouty subjects treated with either urate-lowering agents or placebo to identify determinants of gout flare incidence and tophus size during year 1 of treatment. Reductions from pretreatment serum urate levels influenced flare frequency and tophus size, but the effect of urate level on flare incidence was biphasic.

Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

Background: Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout.

Methods: We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug.

Tophaceous gout: quantitative evaluation by direct physical measurement.

Objective: The absence of accepted standardized methods for monitoring tophaceous gout limits the ability to track tophus progression or regression. This multicenter study assessed intra- and interrater reproducibility of a simple and direct physical measurement.

Methods: The quantitative evaluation was the area (mm2) of each measurable tophus and was determined independently by 2 raters on 2 occasions within 10 days.

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout.

Objective: Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.