Conventional Urate-lowering Therapy Research Articles

Effects of Conventional Uric Acid-Lowering Therapy on Monosodium Urate Crystal Deposits.

Few studies have systematically and quantitatively addressed the impact of urate-lowering therapy on monosodium urate (MSU) deposits. This study was undertaken to analyze the effect of lifestyle measures and conventional urate-lowering therapy on MSU deposits in patients with gout. In this prospective study, subjects with gout according to the American College of Rheumatology/European League Against Rheumatism classification criteria and presence of MSU deposits seen on dual-energy computed tomography (DECT) scans received either lifestyle intervention or conventional urate-lowering therapy for a mean period of 18 months before a follow-up DECT scan. Detected MSU deposits were quantified by volumetric measurement and validated by semiquantitative scoring, and baseline and follow-up measurements were compared. Baseline and follow-up DECT scans were available for all 83 subjects. Six subjects discontinued treatment, and 77 subjects underwent a lifestyle intervention (n = 24) or were treated with allopurinol (n = 29), febuxostat (n = 22), or benzbromarone (n = 2) over the entire observation period. The mean serum uric acid (UA) level decreased from 7.2 to 5.8 mg/dl in the overall population. In patients who discontinued treatment, no change in MSU deposits or serum UA levels was observed. The burden of MSU deposits significantly decreased in patients undergoing lifestyle intervention (MSU volume P = 0.007; MSU score P = 0.001), and in patients treated with allopurinol (MSU volume and score P < 0.001) or febuxostat (MSU volume P < 0.001; MSU score P = 0.001). No significant decline in MSU deposits was noted in patients who discontinued treatment. These data show that lifestyle intervention and xanthine oxidase inhibitors significantly decrease the MSU deposit burden. Hence, conventional gout therapy not only lowers serum UA levels, but also reduces pathologic MSU deposits.

Impact of pegloticase on patient outcomes in refractory gout: current perspectives.

Gout is currently the most frequent cause of inflammatory arthritis worldwide and is responsible for poor health-related quality of life and loss of work productivity. It is caused by high levels of serum urate, leading to the deposition of monosodium urate crystals in joints and soft tissues. This condition is associated with acute flares and, if untreated or refractory, chronic and potentially destructive arthritis and tophi formation. Pegloticase is a recombinant, pegylated uricase used in the treatment of gout patients who fail conventional urate-lowering therapy. In this review, we discuss the impact of pegloticase on patient outcomes in refractory gout. We analyze different parameters, such as plasma uric acid concentration, frequency of flares, tophi reduction, pain, function, quality of life, and safety.

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Wood R et al. Patients with Gout Treated with Conventional Urate-lowering Therapy: Association with Disease Control, Health-related Quality of Life, and Work Productivity

Patients with Gout Treated with Conventional Urate-lowering Therapy: Association with Disease Control, Health-related Quality of Life, and Work Productivity.

Implications of inadequate gout control were assessed through health-related quality of life (HRQOL) and work productivity of patients with gout adequately controlled while taking conventional urate-lowering therapy (ULT) for ≥ 3 months vs those whose gout was inadequately controlled. Retrospective data were drawn from the Adelphi Disease Specific Programme (DSP), a cross-sectional survey of patients with gout in France, Germany, the United Kingdom, and the United States. Patients completed these questionnaires: EQ-5D (3L), Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (HAQ), and Work Productivity and Activity Impairment. Inadequate control was defined as the most recent serum uric acid (SUA) level > 6 mg/dl (> 360 µmol/l) or ≥ 2 flares in the last 12 months; adequate control as SUA level ≤ 6 mg/dl (≤ 360 µmol/l) and 0 flares. Appropriate statistical tests were used to assess differences between groups. There were 836 (69%) inadequately and 368 (31%) adequately controlled gout cases. Mean age was 61 and 63 years and duration of current ULT was 32 and 57 months, respectively. Patients experiencing inadequate control reported significantly worse functioning and HRQOL, as measured by the EQ-5D (0.790 vs 0.877; difference: -0.087; p < 0.001) and PROMIS HAQ (13.21 vs 6.91; difference: 6.30; p < 0.001) scales. Productivity was also more impaired (work time missed: 4.5% vs 1.3%; impairment while working: 19.1% vs 5.2%; overall work impairment: 20.4% vs 5.6%; activity impairment: 20.3% vs 5.3%; all p < 0.001). Less than one-third of patients had gout that was adequately controlled. Those experiencing inadequately controlled gout reported significantly worse functioning, quality of life, and work productivity. Gout treatment strategies to improve disease control may lead to improvements in HRQOL and productivity.

SAT0541 Gout Patients Treated with Conventional Urate-Lowering Therapy: Association between Disease Control and Health-Related Quality of Life

BackgroundGout patients have impaired quality of life compared with the general population [1]. Gout is a chronic, progressive disease and many patients treated with conventional urate-lowering therapy (ULT) are inadequately...

SAT0540 Gout Patients Treated with Conventional Urate-Lowering Therapy: Association between Disease Control and Work Productivity

BackgroundInadequate control of hyperuricaemia in gout patients can lead to loss of work productivity, activity limitations [1] and higher gout-related treatment costs [2]. Some patients treated with conventional urate-lowering therapy...

THU0529 Assessment of the Autoinflammation Impact in Gouty Patients in Spain

BackgroundGout prevalence is increasing mainly due to an increase in the overall longevity and in the prevalence of risk factors such as obesity, alcohol, high intake of purines, hypertension, and...

Lack of change in urate deposition by dual-energy computed tomography among clinically stable patients with long-standing tophaceous gout: a prospective longitudinal study

IntroductionDual-energy computed tomography (DECT) has potential for monitoring urate deposition in patients with gout. The aim of this prospective longitudinal study was to analyse measurement error of DECT urate volume measurement in clinically stable patients with tophaceous gout.MethodsSeventy-three patients with tophaceous gout on stable therapy attended study visits at baseline and twelve months. All patients had a comprehensive clinical assessment including serum urate testing and DECT scanning of both feet. Two readers analysed the DECT scans for the total urate volume in both feet. Analysis included inter-reader intraclass correlation coefficients (ICCs) and limits of agreement, and calculation of the smallest detectable change.ResultsMean (standard deviation) serum urate concentration over the study period was 0.38 (0.09) mmol/L. Urate-lowering therapy was prescribed in 70 (96%) patients. The median (interquartile range) baseline DECT urate volume was 0.49 (0.16, 2.18) cm3, and change in DECT urate volume was -0.01 (-0.40, 0.28) cm3. Inter-reader ICCs were 1.00 for baseline DECT volumes and 0.93 for change values. Inter-reader bias (standard deviation) for baseline volumes was -0.18 (0.63) cm3 and for change was -0.10 (0.93) cm3. The smallest detectable change was 0.91 cm3. There were 47 (64%) patients with baseline DECT urate volumes <0.91 cm3. Higher serum urate concentrations were observed in patients with increased DECT urate volumes above the smallest detectable change (P = 0.006). However, a relationship between changes in DECT urate volumes and serum urate concentrations was not observed in the entire group.ConclusionsIn patients with tophaceous gout on stable conventional urate-lowering therapy the measurement error for DECT urate volume assessment is substantially greater than the median baseline DECT volume. Analysis of patients commencing or intensifying urate-lowering therapy should clarify the optimal use of DECT as a potential outcome measure in studies of chronic gout.

Comorbidity Burden, Healthcare Resource Utilization, and Costs in Chronic Gout Patients Refractory to Conventional Urate-Lowering Therapy

Patients with chronic gout refractory to conventional urate-lowering therapy have high rates of flares and incidence of tophi, which impose a significant disease and potentially economic burden. This study examined healthcare resource use and costs stratified by disease burden. Adult patients diagnosed with gout (ICD-9-CM:274.xx) and having had ≥3 flares defined by clinical surrogates within a 12-month period were selected for the case cohort from the Thomson MarketScan databases (2003/Q3-2008/Q3). Only patients who had received allopurinol treatment and a diagnosis of tophi (ICD-9-CM:274.8x) at any time before the first flare (index date) or within 12 months postindex were included and were matched in a 1:1 ratio with control gout-free subjects. The comorbidity burden, healthcare resource use, and annual healthcare costs (2008 US$) in the 12-month postindex period were compared between both cohorts using regression models adjusted for demographic characteristic and stratified for patients with ≥6 flares. A total of 679 gout patients met the inclusion criteria for the study and had a higher prevalence of comorbidities than their matched controls. Gout cohort had a significantly higher incidence of emergency room, hospitalizations, outpatient visits, and other medical services than did their matched controls (all comparisons, uncorrected P < 0.01). After adjusting for baseline characteristics, the refractory gout cohort incurred an incremental total annual healthcare cost of $10,222 where 40% of the annual medical cost was for gout-related care compared with control cohort (P < 0.01). Patients with refractory gout have a significant economic burden compared with a gout-free population.

Pegloticase

Intravenous pegloticase offers a novel approach to treating chronic gout refractory to conventional therapy. Pegloticase is a recombinant polyethylene glycol-conjugated form of uricase (a uric acid-specific enzyme lacking in humans) that catalyses the oxidation of uric acid to allantoin. In randomized, placebo-controlled, double-blind, 6-month, phase III trials, intravenous pegloticase 8 mg every 2 or 4 weeks provided sustained reductions in plasma uric acid levels to less than the therapeutic target of 6 mg/dL in a substantial proportion of patients with chronic gout who were refractory to, or intolerant of, conventional urate-lowering therapy. Pegloticase 8 mg every 2 weeks was associated with disease-modifying benefits relative to placebo, as shown by significant improvements from baseline in tophi resolution, frequency of gout flares and tender joint count, and clinically relevant and statistically significant improvements from baseline in health-related quality-of-life parameters related to disability, pain and physical function. Pegloticase 8 mg every 4 weeks was also significantly more effective than placebo with regard to most, but not all, of these endpoints. Preliminary data from an open-label extension of the phase III trials indicate that long-term treatment with pegloticase 8 mg every 2 or 4 weeks may maintain plasma uric acid normalization in patients who experienced a sustained uric acid response during the phase III trials. The most common serious adverse events associated with pegloticase are gout flares, infusion reactions and anaphylaxis. In addition, exacerbation of pre-existing congestive heart failure was reported in 2% of patients receiving pegloticase 8 mg every 2 weeks in the phase III trials.

Efficacy and Tolerability of Pegloticase for the Treatment of Chronic Gout in Patients Refractory to Conventional Treatment

Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. clinicaltrials.gov Identifier: NCT00325195.

Quality of Life and Disability in Patients with Treatment-Failure Gout

The relationship between self-reported quality of life and disability and disease severity was evaluated in subjects with treatment-failure gout (n = 110) in a prospective, 52-week, observational study. Subjects had symptomatic crystal-proven gout of at least 2 years' duration and intolerance or refractoriness to conventional urate-lowering therapy. Serum uric acid (sUA) concentration, swollen and tender joint counts, frequency and severity of gout flares, tophus assessments, comorbidities, and patient-reported outcomes data [Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire-Damage Index] were collected. Analyses included correlations of patient-reported outcomes with clinical variables and changes in clinical status. Mean age of study subjects was 59 years. Mean scores on SF-36 physical functioning subscales were 34.2-46.8, analogous to persons aged >or= 75 years in the general population. Subjects with more severe gout at baseline had worse health-related quality of life (HRQOL) in all areas (p < 0.02 for all measures), compared to patients with mild-moderate disease. Number of flares reported in past year, number of tender joints, swollen joints, and tophi correlated significantly with some or all HRQOL and disability measures. sUA was not significantly correlated with any HRQOL or disability measure. Subjects with comorbidities experienced worse physical, but not mental, functioning. Severe gout is associated with poor HRQOL and disability, especially for patients who experience more gout flares and have a greater number of involved joints. Subject perceptions of gout-related functioning and pain severity appear to be highly sensitive indicators of HRQOL and disability.