Target Serum Urate Level Research Articles

Weight Reduction and Target Serum Urate Level: A Longitudinal Study of Annual Medical Examination.

Our objective was to evaluate associations of weight reduction with serum urate (SU) changes and achieving an SU level <6 mg/dL in the real-world setting, outside of specific weight reduction interventions. We analyzed systematically collected data of annual medical examination participants from October 2012 to October 2022. Exposure was weight change (increase or decrease) between two consecutive visits, categorized as minimal (≤0.9 kg, reference), small (1.0-4.9 kg), moderate (5.0-9.9 kg), and large (≥10 kg). Outcomes included SU changes between two consecutive visits and achieving an SU level <6 mg/dL in participants with hyperuricemia (SU level ≥7 mg/dL at the previous visit). We identified 58,630 eligible participants (median age 46 years, 51.3% female, 19.4% with overweight, median SU level 5.3 mg/dL, and 5.6% with a history of gout and/or hyperuricemia) with 336,814 visits over a median of 5.3 years. After adjustment for relevant covariates, linear general estimating equations estimated mean SU changes based on observed weight reductions (vs minimal changes) were as follows: small, -0.10 mg/dL (95% confidence interval [CI] -0.10 to -0.09 mg/dL); moderate, -0.34 mg/dL (95% CI -0.36 to -0.32 mg/dL); and large, -0.64 (95% CI -0.70 to -0.58 mg/dL). In participants with hyperuricemia, adjusted relative risks for achieving an SU level <6 mg/dL by modified Poisson regression were 1.25 (95% CI 1.15-1.37) in small weight reductions, 2.82 (95% CI 2.43-3.27) in moderate weight reductions, and 5.27 (95% CI 4.15-6.70) in large weight reductions, with corresponding numbers needed to treat of 61.1 for small weight reductions, 8.5 for moderate weight reductions, and 3.6 for large weight reductions. Small weight reductions were associated with only small SU changes. Some participants with hyperuricemia can achieve the target SU level with moderate to large weight reductions.

Controversies and practical management of patients with gout and chronic kidney disease

Uric acid is a toxin retained with advancing kidney disease. Clinical manifestations of hyperuricemia include gout and systemic inflammation that are associated with increased risk for cardiovascular mortality. As many as one third of all patients with chronic kidney disease (CKD) have a history of gout, yet <25% of these patients are effectively treated to target serum urate levels of ≤6 mg/dL. A major reason for ineffective management of gout and hyperuricemia is the complexity in managing these patients, with some medications contraindicated, others requiring special dosing, potential drug interactions, and other factors. Consequently, many nephrologists do not primarily manage gout despite it being a common complication of CKD, leaving management to the primary physician or rheumatologist. We believe that kidney specialists should consider gout as a major complication of CKD and actively manage it in their patients. Here, we present insights from nephrologists and rheumatologists on a team approach to gout management that includes the nephrologist.

Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker

IntroductionUntreated gout is characterised by monosodium urate (MSU) crystal accumulation responsible for recurrent flares that are commonly separated by asymptomatic phases. Both phases are inflammatory conditions of variable intensity. Gout...

Predictors of Inadequate Serum Urate Response to Low-Dose Febuxostat in Male Patients with Gout.

This study aimed to understand predictors of inadequate response (IR) to low-dose febuxostat treatment based on clinical variables. We pooled data from 340 patients of an observational cohort and two clinical trials who received febuxostat 20 mg/day for at least 3 months. IR was defined as failure to reach the target serum urate level (sUA<6 mg/dL) at any time point during 3 months treatment. The potential predictors associated with short- or mid-term febuxostat IR after pooling the three cohorts were explored using mixed-effect logistic analysis. Machine learning models were performed to evaluate the predictors for IR using the pooled data as the discovery set and validated in an external test set. Of the 340 patients, 68.9% and 51.8% were non-responders to low-dose febuxostat during short- and mid-term follow-up, respectively. Serum urate and triglyceride (TG) levels were significantly associated with febuxostat IR, but were also selected as significant features by LASSO analysis combined with age, BMI, and C-reactive protein (CRP). These five features in combination, using the best-performing stochastic gradient descent classifier, achieved an area under the receiver operating characteristic curve of 0.873 (95% CI [0.763, 0.942]) and 0.706 (95% CI [0.636, 0.727]) in the internal and external test sets, respectively, to predict febuxostat IR. Response to low-dose febuxostat is associated with early sUA improvement in individual patients, as well as patient age, BMI, and levels of TG and CRP.

Febuxostat dose requirement according to renal function in patients who achieve target serum urate levels: A retrospective cohort study

ObjectivesTo determine the febuxostat dose requirement according to renal function in patients who achieve target serum urate (SU) levels. MethodsOf 3153 gout patients who underwent febuxostat treatment, 873 patients with an initial SU level>6mg/dL were included and categorized by the estimated glomerular filtration rate: normal, chronic kidney disease (CKD) stage 3, and stages 4–5. Ninety-five patients with insufficient follow-up were further excluded. The dose of febuxostat in patients who achieved the SU target (< 6mg/dL) was defined as the average daily dosage at the time of SU target achievement. ResultsThe cohort of 778 gout patients had a median age of 52.0 years (IQR, 41.0–63.0) and comprised 711 (91.4%) men. The mean SU at febuxostat initiation was higher in the CKD 4–5 (9.6 [± 3.1] mg/dL) than in the other groups (CKD 3, 8.7 [± 1.7]; normal, 8.4 [± 1.7]; P<0.001). Patients achieved target SU at a median of 4.0 (1.9–9.6) months and in those who achieved target SU, the dose of febuxostat at the time of SU target achievement was significantly lower in the CKD 4–5 group (50.0 [± 16.5] mg) than in the other groups (vs. CKD stage 3, 60.0 [± 19.5] mg; P<0.01, vs. normal, 60.0 [± 19.8] mg; P<0.01). Furthermore, CKD stage 4–5 had a negative correlation with the febuxostat dose requirement (Beta: –2.334, P<0.05). ConclusionAmong patients who achieved SU target, those with severely decreased renal function (CKD 4–5) required a lower febuxostat dose to achieve the target SU level compared to patients with normal or mild renal impairment.

Mechanisms and rationale for uricase use in patients with gout.

Xanthine oxidase inhibitors such as allopurinol and febuxostat have been the mainstay urate-lowering therapy (ULT) for treating hyperuricaemia in patients with gout. However, not all patients receiving oral ULT achieve the target serum urate level, in part because some patients cannot tolerate, or have actual or misconceived contraindications to, their use, mainly due to comorbidities. ULT dosage is also limited by formularies and clinical inertia. This failure to sufficiently lower serum urate levels can lead to difficult-to-treat or uncontrolled gout, usually due to poorly managed and/or under-treated gout. In species other than humans, uricase (urate oxidase) converts urate to allantoin, which is more soluble in urine than uric acid. Exogenic uricases are an exciting therapeutic option for patients with gout. They can be viewed as enzyme replacement therapy. Uricases are being used to treat uncontrolled gout, and can achieve rapid reduction of hyperuricaemia, dramatic resolution of tophi, decreased chronic joint pain and improved quality of life. Availability, cost and uricase immunogenicity have limited their use. Uricases could become a leading choice in severe and difficult-to-treat gout as induction and/or debulking therapy (that is, for lowering of the urate pool) to be followed by chronic oral ULT. This Review summarizes the evidence regarding available uricases and those in the pipeline, their debulking effect and their outcomes related to gout and beyond.

Lowering serum urate with urate-lowering therapy to target and incident fracture among people with gout.

Gout is associated with a higher risk of fracture; however, the associations of hyperuricemia and urate-lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e., <360 μmol/L) reduces risk of fracture among people with gout. We emulated analyses of a hypothetical target trial using a "cloning, censoring, and weighting" approach to examine the association between lowering SU with ULT to the target levels and the risk of fracture using data from The Health Improvement Network, a United Kingdom primary care database. Individuals with gout who were 40 years or older and initiated ULT were included in the study. Among 28,554 people with gout, the 5-year risk of hip fracture was 0.5% for the "achieving the target SU level" arm and 0.8% for "not achieving the target SU level" arm, respectively. The risk difference and hazard ratio for "achieving the target SU level" arm was -0.3% (95% confidence interval [CI]: -0.5% to -0.1%) and 0.66 (95% CI: 0.46 to 0.93), respectively, compared with "not achieving the target SU level". Similar results were observed when the associations of lowering SU level with ULT to the target levels with the risk of composite fracture, major osteoporotic fracture, vertebral fracture, and non-vertebral fracture were assessed. In this population-based study, lowering the SU level with ULT to the guideline-based target level is associated with a lower risk of incident fracture in people with gout.

Musculoskeletal Ultrasound in Monitoring the Efficacy of Gout: A Prospective Study Based on Tophus and Double Contour Sign

In patients with gout receiving uric acid-lowering therapy, musculoskeletal ultrasound has the potential to observe changes in gout lesions. To analyze the effectiveness of uric acid-lowering therapy in patients with gout over one year using musculoskeletal ultrasound as a monitoring technique. Prospective cohort study. A total of 215 patients meeting the 1977 American College of Rheumatology gout classification criteria and treated with uric acid-lowering therapy were separated into two groups, treat-to-target and treat-to-non-target depending on the target serum urate levels. Lower extremity joints were evaluated by ultrasound before therapy (M0), as well as three (M3), six (M6), and twelve (M12) months after therapy. At various moments during uric acid-lowering therapy, the tophus size and the semiquantitative ultrasound scoring system of double contour sign were measured in the treat-to-target and treat-to-non-target groups. Ninety-five tophi (45 in treat-to-target and 50 in treat-to-non-target) and sixty-seven double contour sign (34 in treat-to-target and 33 in treat-to-non-target) were evaluated longitudinally. In both groups, the long diameter, short diameter, and area of tophus in treat-to-target decreased as the duration of uric acid-lowering treatment increased. Differences in the long diameter of tophus between M12 and M0, M3 and M6 were statistically significant (P < 0.05), while differences between the other time points were not significant (P > 0.05). No statistically significant differences were observed in the short diameter and the area of tophus between M0 and M3 (P > 0.05), while there were statistically significant differences between other periods (P < 0.05). In treat-to-non-target, the long diameter, short diameter, and area of tophus showed a slight increase at different uric acid-lowering therapy time points. The differences in the long diameter, short diameter, and area of tophus at different uric acid-lowering therapy time points were not significant (P > 0.05). The semiquantitative ultrasound scoring system of double contour sign of treat-to-target and treat-to-non-target showed a decreasing trend with increasing uric acid-lowering therapy time, with a more pronounced drop in treat-to-target than treat-to-non-target. In treat-to-target, the difference in the semiquantitative ultrasound scoring system of double contour sign at each uric acidlowering therapy time point was significant (P < 0.05). In treat-tonon- target, the difference in semiquantitative ultrasound scoring system of double contour sign scores between M0 and M3 was not statistically significant (P >0.05), but it was statistically significant for the remaining time points (P < 0.05). After one year of uric acid-lowering therapy in patients with gout, an ultrasound indicated that the size of tophus and the semiquantitative ultrasound scoring system of double contour sign score decreased dramatically in the treat-to-target group. Semiquantitative ultrasound scoring system of double contour sign score was dramatically reduced in the treat-to-non-target group, but the size of the tophus remained the same. Therefore, musculoskeletal ultrasound is an effective tool to monitor the efficacy of uric acid-lowering therapy.

PS-C04-6: ASSOCIATION BETWEEN SERUM URATE LEVEL AND CAROTID ATHEROSCLEROSIS: AN INSIGHT FROM A POST-HOC ANALYSIS OF THE RANDOMIZED CLINICAL TRIAL (PRIZE)

Objectives: Elevated serum urate (SU) levels are associated with arterial atherosclerosis and subsequent cardiovascular events. However, an optimal therapeutic target SU level for delaying atherosclerotic progression in patients with hyperuricemia remains uncertain. The aim of this analysis was to assess an association between changes in SU level and carotid intima-media thickness (IMT) to examine whether an optimal SU concentration exists to delay atherosclerotic progression. Design and method: This was a post-hoc analysis of the PRIZE (program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled) study of Japanese adults with asymptomatic hyperuricemia (UMIN000041322). Among the full analysis set population treated with febuxostat (n = 239), subjects who had both data on SU level and mean common carotid artery (CCA)-IMT at baseline and 24 months were included in the present analysis. The primary endpoint of this analysis was an association between changes in SU levels and mean CCA-IMT after 24 months of febuxostat treatment. Results: A total of 204 eligible subjects were included in this analysis. The mean age was 69.1 +/- 9.6 years, and one fifth were female. Most had a history of treated hypertension and/or dyslipidemia. The mean baseline SU level was 7.7 ± 1.0 mg/dL, and febuxostat treatment significantly reduced SU concentrations at 24 months (estimated mean change -3.1 mg/dL, 95% confidence interval -3.2 to -2.9). A multivariable linear regression analysis revealed that a reduction in SU level was associated with changes in mean CCA-IMT values at 24 months (Figure A). In contrast, the achieved SU concentrations were not associated with changes in mean CCA-IMT at 24 months (Figure B). Conclusion: A greater reduction in SU, but not its achieved concentrations, may be associated with delayed progression of carotid IMT in patients with asymptomatic hyperuricemia treated with febuxostat.

Hyperuricemia: contemporary treatment in patients with cardiovascular disease

The prevalence of hyperuricemia is due to the epidemic of obesity, changes in eating behavior in the population with the rise of purines, alcohol and fructose consumption, as well as the increased use of diuretics. It’s important to mention that over the past 20 years there has been an increase in the prevalence of such concomitant diseases and conditions as arterial hypertension (+15%), diabetes mellitus (+19%), decreased kidney function (+17%), hyperlipidemia (+40%) and obesity (+19%). Hyperuricemia (and/or gout) can be both a cause and a consequence of various comorbid conditions. That is why their treatment is closely connected with the treatments of hyperuricemia, especially of asymptomatic one.It’s important to determine not only the upper limit of the uric acid in patients, when the therapy is being initiated, but to assess the target levels of uric acid, that must be achieved in patients receiving optimal treatment.In this review article the main principles of both non-pharmacological and pharmacological treatment in patients with cardiovascular diseases are described. The need for medical treatment, target serum urate levels in patients with cardiovascular risk factors are discussed, as well as further perspectives in the field of research in patients with hyperuricemia and cardiovascular diseases.Allopurinol is currently the key drug prescribed to patients with hyperuricemia and cardiovascular risk factors. The most important advantage is its safety profile. Patients receiving renal replacement therapy can also safely receive the drug.The need to reduce the level of uric acid in patients with cardiovascular disease is currently beyond doubt. In the group of patients with additional risk factors, such as diabetes mellitus, metabolic syndrome and CKD, lifestyle modification in combination with urate-lowering therapy improves both the quality of life and prognosis. Currently, allopurinol is the drug of choice for the treatment of AH in combination with AH, taking into account both the efficacy and safety of its administration to this group of patients. However, it is obvious that further studies with clearer inclusion criteria are needed to analyze the effect of therapy on cardiovascular events, as well as combined endpoints.

Association between serum urate level and carotid atherosclerosis: an insight from a post hoc analysis of the PRIZE randomised clinical trial

ObjectivesElevated serum urate (SU) levels are associated with arterial atherosclerosis and subsequent cardiovascular events. However, an optimal therapeutic target SU level for delaying atherosclerotic progression in patients with hyperuricaemia remains...

Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management

BackgroundThe relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues.MethodsParticipants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events.ResultsThis study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P<0.001 for noninferiority). Overall, 80% of participants achieved mean target urates during phase 2 with no differences by treatment. There were no treatment differences (including cardiovascular events) in serious adverse events.ConclusionsAllopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; ClinicalTrials.gov identifier, NCT02579096.)

Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease : A Population-Based Cohort Study.

Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown. To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD. Cohort study. The Health Improvement Network U.K. primary care database (2000 to 2019). Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD. The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators. Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07). Residual confounding cannot be ruled out. In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD. Project Program of National Clinical Research Center for Geriatric Disorders.

Dotinurad: a novel selective urate reabsorption inhibitor for the treatment of hyperuricemia and gout

ABSTRACT Introduction Gout is an inflammatory disease triggered by deposition of urate crystals secondary to longstanding hyperuricemia, and its management implies both the treatment of flares and management of hyperuricemia. Dotinurad is a selective urate reabsorption inhibitor (SURI), potently inhibits urate transporter 1 in the apical surface of renal proximal tubular cells, and has been approved for the treatment of gout and hyperuricemia in Japan. Areas covered This overview of dotinurad covers nonclinical and clinical pharmacology studies in special populations and its efficacy and safety in Japanese hyperuricemic patients with and without gout. Expert opinion Dotinurad, as an SURI, is expected to inhibit urate reabsorption more effectively than conventional urate-lowering agents. It is noninferior to benzbromarone or febuxostat in reducing serum urate levels in hyperuricemic patients with or without gout. Its efficacy is not attenuated in patients with mild to moderate renal impairment or with hepatic impairment. At a maintenance dose of 2 or 4 mg once daily, most patients achieved the target serum urate level of ≤6 mg/dL in a long-term study. No findings that raised safety concerns, including liver injury, were identified. Dotinurad is expected to be a new therapeutic option in hyperuricemic patients with and without gout.

Epidemiology of gout in Hong Kong: a population-based study from 2006 to 2016

ObjectiveTo determine the incidence and prevalence of gout in the general population and the utilisation of urate-lowering therapy (ULT) among patients with gout in Hong Kong.MethodsA total of 2,741,862 subjects who attended any outpatient clinics or accident and emergency department (with or without hospitalisation) in 2005 and did not die before 2006 were identified from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority in Hong Kong. All subjects were followed until the end of 2016 or death.Demographics, diagnosis of gout, serum urate levels, and ULT prescriptions were retrieved from CDARS. Gout was defined by the diagnosis codes in CDARS. The serum urate levels achieved after prescribing ULT were the means of all serum urate levels measured 6 months after prescriptions. Results were analysed by R version 3.3.3 with package ‘prevalence’ version 0.4.0.ResultsThe crude incidence of gout increased from 113.05/100,000 person-years (PY) in 2006 to 211.62/100,000 PY in 2016. The crude prevalence of gout increased from 1.56% in 2006 to 2.92% in 2016. Only 25.55% of patients with gout were prescribed ULT in 2016. 35.8% of patients treated with ULT were able to achieve the target serum urate level of < 6 mg/dL.ConclusionsPopulation ageing as well as other risk factors contributed to an increase in the incidence and prevalence of gout in Hong Kong. In 2016, the crude prevalence of gout in Hong Kong was comparable to that in many western countries. However, only one in four patients with gout in Hong Kong was prescribed ULT.

Achievement of the target serum urate level among patients with gout treated with allopurinol or febuxostat in an arthritis clinic in the Philippines

Objective Gout is an important cause of disability among Filipinos, despite measures for effective management. This study aims to determine attainment of target serum uric acid level (SUA ≤ 6 mg/dl) among patients with gout given urate-lowering therapy (ULT) over 6–12 months. Methods This is a single-center, prospective cohort study conducted in one adult Arthritis Clinic at the University of the Philippines-Philippine General Hospital which included 138 patients with gout (1977 ACR criteria), SUA ≥ 6 mg/dl prior to ULT, initiated on ULT (allopurinol or febuxostat), with six months minimum follow-up and with SUA determination post-treatment. Results 37.7% (52/138) and 36.2% (50/138), achieved target SUA at 6 and 12 months. The factors associated with achieving target SUA in 6 months are BMI > 25 kg/m2 [OR 6.98, 95% confidence interval (CI) 1.44–33.88, p value = .016], allopurinol dose ≥ 300 mg (OR 15.76, 95% CI 2.24–111.06, p value = .006), and baseline SUA (OR 0.52, 95% CI 0.33–0.82, p value = .005). The factors associated with achieving target SUA in 12 months are employment (OR 5.51, 95% CI 1.00–30.33, p value = .050), baseline SUA (OR 0.45, 95% CI 0.28–0.74, p value = .002), and age at onset of gout (OR 1.08, 95% CI 1.01–1.15, p value = .026). Conclusion Target SUA level was not achieved at 6 and 12 months of ULT in most of this cohort. This mirrors the deficient control of gout and should urge health professionals to fully study and address the problem.

Comparison of efficacy and safety of urate-lowering therapies for hyperuricemic patients with gout: a meta-analysis of randomized, controlled trials.

To assess the efficacy and safety of the commonly used urate-lowering therapies (ULTs): febuxostat, allopurinol, and lesinurad in hyperuricemic patients with gout. We included all randomized controlled trials (RCTs) that compared ULTs with placebo or head to head. The primary efficacy endpoint was the proportion of subjects achieving the target serum urate (SU) level at month 6. Safety outcomes included total adverse events (AEs), serious AEs, withdrawals due to AEs, and AEs per organ system. A Bayesian network model was used to compare all ULTs with placebo and among themselves. Fifteen RCTs were included for the analysis, in which 7968 patients were randomly assigned to take either placebo or one of 11 ULTs: allopurinol, febuxostat 40/80/120/240mg/day, lesinurad 400mg/day, lesinurad 200/400/600mg/day plus allopurinol, and lesinurad 200/400mg/day plus febuxostat. All ULTs were effective in achieving the target SU level at month 6 compared with placebo (ORs between 26.81 and 1928). Febuxostat 80/120/240mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. Furthermore, the lesinurad combination with xanthine oxidase inhibitor (XOI) groups had a higher proportion of patients achieving the target SU level than the febuxostat 40mg/day group (ORs between 2.89 and 9.17), the allopurinol group (ORs between 3.56 and 11.27), or the lesinurad 400mg/day monotherapy group (ORs between 12.30 and 39.17) but might have a high risk of AEs. All ULTs are effective in achieving the target SU level compared with placebo in hyperuricemic patients with gout. Lesinurad in combination with febuxostat or allopurinol is effective in urate lowering, especially for patients with inadequate response to XOI monotherapy. Key Points • All urate-lowering therapies (ULTs) were effective in achieving the target serum urate (SU) level at month 6 compared with placebo in hyperuricemic patients with gout. • Febuxostat 80/120/240mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. • Lesinurad in combination with febuxostat or allopurinol was effective in urate lowering, especially for patients with inadequate response to xanthine oxidase inhibitor monotherapy, but might have a high risk of AEs.

Efficacy of febuxostat versus allopurinol and the predictors of achieving target serum urate in a cohort of Thai people with gout.

The objectives of our study were to compare the efficacy of febuxostat with allopurinol in Thai subjects with gout, as well as to determine the predictive factors of responsiveness to urate-lowering agents and to evaluate the safety of febuxostat in a real-world setting. The study was a retrospective cohort study; a total of 354 gout patients were recruited from February 2015 to November 2018. The patients were categorized according to prescription of allopurinol or febuxostat. Demographic data, comorbidities, concomitant medications, gout-related clinical parameters, and the laboratory results were collected. The serial serum urate (sUA) levels were recorded at the beginning of the treatment (baseline), and after treatment at 12weeks, 18weeks, and 27weeks. The primary efficacy endpoint was the achievement of target urate of < 6mg/dl in people taking febuxostat, compared with those taking allopurinol. The secondary endpoints were the predictive factors of achieving target urate level and adverse drug reactions in patients taking febuxostat. Multivariable regression analysis was used to determine factors associated with achieving target serum urate. After the treatment, the febuxostat groups had significantly lower mean sUA compared with the allopurinol groups across all follow-up periods. The proportion of people who achieved target serum urate was also higher in the febuxostat groups compared with the allopurinol groups throughout the follow-up periods. The multivariable regression analysis showed that febuxostat 40mg (OR = 10.96 (95% CI 4.32-27.80); p value < 0.001), febuxostat 80mg (OR = 9.54 (95% CI 3.91-23.28), smoking (OR = 2.35 (95% CI 1.13-4.91); p value = 0.023), and low baseline serum urate (OR = 0.62 (95% CI 0.52-0.74); p value <0.001) were associated with the achievement of target serum urate. No adverse drug reaction from febuxostat was observed even among people with renal insufficiency. In a Thai cohort, people receiving febuxostat are more likely to achieve target serum urate level, compared with people receiving allopurinol. Febuxostat (40 or 80mg), smoking, and low baseline serum urate were associated with the achievement of target serum urate. • Febuxostat showed superior urate-lowering efficacy compared with allopurinol in an Asian population. • In addition to febuxostat, lower baseline serum urate level and history of smoking were associated with achieving target serum urate in gout patients.

Management of patients with gout and achievement of target serum urate levels at a tertiary rheumatology service in Australia.

Gout is common crystal arthritis that is often managed sub-optimally. To determine what proportion of patients treated for gout by the tertiary level rheumatology service at the Royal Brisbane Hospital between 2014 and 2018 reached target serum urate (SU) levels. Secondary aims included exploring the demographic characteristics of those who did and did not reach target. The records of patients who were treated at least once either as in inpatient or outpatient by the rheumatology service at the Royal Brisbane Hospital between 1 January 2014 and 31 December 2018 were reviewed. Clinical status, treatment characteristics and outcome were recorded and analysed. There were 129 patients who met the inclusion criteria for the study, the majority of patients were male and 39% had tophaceous gout. Fifty-four (42%) had been intentionally discharged from clinic, 50 (85%) of those patients had reached their SU target, the remaining eight (15%) were discharged with a plan for other services to continue their therapy to reach SU target. Forty patients (31%) had ongoing follow up, with 16 (40%) of these at target and 24 (60%) not at target. Thirty-five (27%) were not attending, five (4%) had died and 30 (23%) had failed to attend follow-up appointments, none of these patients was at target at their last known SU level. Despite effective therapy the number of patients treated for gout at a large public metropolitan teaching hospital reaching SU target was low. Almost one-quarter of patients in the study discontinued contact with the clinic. The reasons for this are not clear and are likely multifactorial.

Facilitating equitable prevention and management of gout for Māori in Northland, New Zealand, through a collaborative primary care approach.

INTRODUCTION The Gout Stop Programme was developed for primary care in Northland, New Zealand, to address inequitable health outcomes for Māori and Pacific people with gout. AIM The aim of the programme was to make it easier for clinicians to prescribe urate-lowering treatment, facilitate patient adherence through education and support, and reduce barriers to gout prevention and long-term management. METHODS From 2015 to 2017, patients with acute gout who met inclusion criteria were prescribed treatment according to a 'Gout Stop Pack' option, based on renal function and diabetes status. Patients were monitored by community pharmacists. Gout educators and a Gout Kaiāwhina (community support worker) provided education and support to patients and whānau (families). Patient completion of the programme and outcomes, according to target serum urate level, were recorded. Patient experience was documented using a questionnaire and rating scale. RESULTS In total, 160 clinicians prescribed therapy at 887 patient presentations; 71% were Māori and Pacific patients. The completion rate was 55% in this group and 84% for the non-Māori and non-Pacific group. In the Māori and Pacific group, 40% reached the target serum urate level (≤0.36 mmol L-1) in 91 days, and 26% required further titration. In the non-Māori/non-Pacific group, these rates were 51% and 19% respectively. Following programme completion, 68% of Māori and Pacific patients and 65% of non-Māori and non-Pacific patients continued to take allopurinol. The 21 patients interviewed rated the programme as excellent or very good. DISCUSSION Culturally appropriate education and support for patients and the primary care team was essential. Collaboration between prescribers, community pharmacists and support workers reduced barriers to initiating prevention and long-term urate-lowering treatment and urate testing in this high-needs gout population.