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Background: Uncontrolled gout can cause articular impairment but is also associated with a global and cardiovascular excess mortality, especially in dialysis population. Data documented within existing research is not conclusive regarding gout flares evolution during hemodialysis and their control by urate lowering therapy (ULT). Without clear guidelines concerning hemodialysis patients management with chronic gout, this study proposes to investigate whether gout flare incidence reduction could be observed on this population treated by urate lowering therapy versus patients without treatment. Methods: We performed a retrospective cohort study in two hemodialysis centers in France. Were selected patients over 18 years old with a gout history who started hemodialysis between January 2005 and September 2015. Demographics and clinicals data were recorded at hemodialysis start and throughout 5 years of follow up. Gout flare was defined as presence of uric acid crystal in joint punction or clinically diagnosed as such with a colchicine prescription. All statistical analysis were performed in SAS® version 9.4 (SAS Institute Inc., Cary, NC). Results: One hundred eighty-one patients have been included, mean age at dialysis initiation was 68.6 years (± 12.4) with 72% of men, 54% were treated by ULT: 89.7% by allopurinol and 9.3% by febuxostat. One patient received both treatments successively. After hemodialysis initiation, 35.36% patients had experienced at least one gout flare. The appearance of at least one gout flare concerned 50% of patients in no ULT group and 22.68% patients in ULT group (p = 0.0002). Dialysis efficiency was measured at regular interval during follow-up and was similar in both groups. To study the association strength between clinical factors and gout flares occurrences, a Cox model was performed; ULT is a protector factor of gout flare (HR:0,42, CI 95: 0,25-0,71). The proportion of serum urate values within the target (median 53% vs 29.3%, p < 0.0001) was significantly higher in ULT group versus no ULT group (median 53% vs 29.3%, p < 0.0001). Conclusion: Urate lowering therapy limit new gout flares occurrence in hemodialysis patients with gout historyCollaboration between rheumatologists and nephrologists may help to update guidelines for urate-lowering therapies in patients on dialysis. [ABSTRACT FROM AUTHOR]

Abstract Background Uncontrolled gout can cause articular impairment but is also associated with a global and cardiovascular excess mortality, especially in dialysis population. Data documented within existing research is not conclusive regarding gout flares evolution during hemodialysis and their control by urate lowering therapy (ULT). Without clear guidelines concerning hemodialysis patients management with chronic gout, this study proposes to investigate whether gout flare incidence reduction could be observed on this population treated by urate lowering therapy versus patients without treatment. Methods We performed a retrospective cohort study in two hemodialysis centers in France. Were selected patients over 18 years old with a gout history who started hemodialysis between January 2005 and September 2015. Demographics and clinicals data were recorded at hemodialysis start and throughout 5 years of follow up. Gout flare was defined as presence of uric acid crystal in joint punction or clinically diagnosed as such with a colchicine prescription. All statistical analysis were performed in SAS® version 9.4 (SAS Institute Inc., Cary, NC). Results One hundred eighty-one patients have been included, mean age at dialysis initiation was 68.6 years (± 12.4) with 72% of men, 54% were treated by ULT: 89.7% by allopurinol and 9.3% by febuxostat. One patient received both treatments successively. After hemodialysis initiation, 35.36% patients had experienced at least one gout flare. The appearance of at least one gout flare concerned 50% of patients in no ULT group and 22.68% patients in ULT group (p = 0.0002). Dialysis efficiency was measured at regular interval during follow-up and was similar in both groups. To study the association strength between clinical factors and gout flares occurrences, a Cox model was performed; ULT is a protector factor of gout flare (HR:0,42, CI 95: 0,25-0,71). The proportion of serum urate values within the target (median 53% vs 29.3%, p

Aims: The aim of this study was to estimate adherence to urate‐lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient‐reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day). Methods: Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12‐month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%. We measured the correlation between the two methods of calculating PDC using a Wilcoxon signed rank test. Agreement between ULT‐taking status (self‐reports) and ULT‐dispensed status (PBS records) was tested with Cohen's kappa (κ), and positive and negative percent agreement. Results: Allopurinol was prescribed in 93.5% of participants taking ULT. Their self‐reported mean daily dose (SD) was 291 (167) mg/day. Mean PDC (SD) for allopurinol was 83% (21%) calculated using self‐reported dose, and 63% (24%) using WHO's DDD. Sixty‐three percent of allopurinol users were identified as adherent (PDC ≥80%) using self‐reported dose. There was good agreement between self‐reported ULT use and PBS dispensing claims (κ = 0.708, P <.001; positive percent agreement = 90%, negative percent agreement = 82%). Conclusions: Participant‐reported allopurinol daily doses, in addition to PBS dispensing claims, may enhance confidence in estimating PDC and adherence compared to using DDD. This approach improves adherence estimations from pharmaceutical claims datasets for medications where daily doses vary between individuals or where there is a wide therapeutic dose range. [ABSTRACT FROM AUTHOR]

Abstract Background Gout is the most common inflammatory arthritis and is almost exclusively managed in primary care, however the course and severity of the condition is variable and poorly characterised. This research aims improve understanding about the frequency of, and factors associated with, gout flares in the UK and characterise the factors associated with the initiation of ULT. Methods Using the Clinical Practice Research Database, patients with a coded incident gout diagnosis without a prior prescription for urate-lowering therapy (ULT) were identified. Gout flares post diagnosis and ULT initiation were identified through prescribing and coded data. Patient characteristics, co-morbidities and co-prescribing were co-variants. Factors associated with gout flares and ULT initiation were analysed using cox-proportional hazard model and logistic regression. Results Fifty-one thousand seven hundred eighty-four patients were identified: 18,605 (35.9%, 95%CI 35.5–36.3%) had experienced ≥ 1 recurrent flare, 17.4% (95%CI 17.1–17.8%) within 12 months of diagnosis. Male sex, black ethnicity, higher BMI, heart failure, CKD, CVD and diuretic use were associated with flares, with the highest HR seen with high serum urate levels (≥ 540 µmol/L HR 4.63, 95%CI 4.03–5.31). ULT initiation was associated with similar variables, although higher alcohol intake and older age were associated with lower odds of ULT initiation but were not associated with flares. ULT was initiated in 27.7% (95%CI 27.3–28.0%): 5.7% (95%CI 5.5–5.9%) within 12 months of diagnosis. ULT initiation rates were higher in patients with recurrent flares. Conclusion Approximately one in six people with incident gout had a second flare within 12 months. Factors associated with flare recurrence and ULT initiation were similar, but ULT initiation occurred later after diagnosis than previously thought.

Background: Gout is the most common inflammatory arthritis and is almost exclusively managed in primary care, however the course and severity of the condition is variable and poorly characterised. This research aims improve understanding about the frequency of, and factors associated with, gout flares in the UK and characterise the factors associated with the initiation of ULT. Methods: Using the Clinical Practice Research Database, patients with a coded incident gout diagnosis without a prior prescription for urate-lowering therapy (ULT) were identified. Gout flares post diagnosis and ULT initiation were identified through prescribing and coded data. Patient characteristics, co-morbidities and co-prescribing were co-variants. Factors associated with gout flares and ULT initiation were analysed using cox-proportional hazard model and logistic regression. Results: Fifty-one thousand seven hundred eighty-four patients were identified: 18,605 (35.9%, 95%CI 35.5–36.3%) had experienced ≥ 1 recurrent flare, 17.4% (95%CI 17.1–17.8%) within 12 months of diagnosis. Male sex, black ethnicity, higher BMI, heart failure, CKD, CVD and diuretic use were associated with flares, with the highest HR seen with high serum urate levels (≥ 540 µmol/L HR 4.63, 95%CI 4.03–5.31). ULT initiation was associated with similar variables, although higher alcohol intake and older age were associated with lower odds of ULT initiation but were not associated with flares. ULT was initiated in 27.7% (95%CI 27.3–28.0%): 5.7% (95%CI 5.5–5.9%) within 12 months of diagnosis. ULT initiation rates were higher in patients with recurrent flares. Conclusion: Approximately one in six people with incident gout had a second flare within 12 months. Factors associated with flare recurrence and ULT initiation were similar, but ULT initiation occurred later after diagnosis than previously thought. [ABSTRACT FROM AUTHOR]

Background: We sought to examine the cardiovascular safety of intensive treat-to-target serum urate strategies for gout using Medicare claims data linked to electronic health record laboratory data. Methods: We selected patients with gout who initiated urate-lowering therapy. We emulated a hypothetical trial comparing the rate of major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) among seven different strategies over 24 months. Three aspects were considered in defining increasingly intensive strategies: (1) continuation of uratelowering therapy, (2) serum urate monitoring, and (3) modification of urate-lowering therapy when serum urate >6 mg/dl. We applied the "clone-censor-weight" method to account for baseline and timevarying confounding. Results: We identified 4402 patients with gout who initiated uratelowering therapy (mean age 77; male 60%). During a total of 6611 person-years (PY) of follow-up under usual care, the rate of major cardiovascular events (first and recurrent) was 4.5/100 PY (95% CI = 4.0, 5.1). The rate ratios (RRs) suggested reductions (RR point estimates 0.88-0.84) compared with usual care. All 95% CIs were imprecise, but their upper bounds excluded substantial increase in RRs. RRs were closer to 1.0 for the analysis focusing on the first major adverse cardiovascular event during follow-up and on comparison to the strategy requiring continuation of urate-lowering therapy (but not necessarily titration). Conclusions: Our treatment strategy trial emulation did not find increased risk of major adverse cardiovascular events with intensive urate-lowering strategies. Results may provide reassurance of the cardiovascular safety of intensive treat-to-target serum urate strategies recommended by rheumatology societies. [ABSTRACT FROM AUTHOR]

Gout is a commonly treated inflammatory arthritis that is often managed in the primary care setting. This disease is prevalent among the multi-ethnic Malaysian population. Unfortunately, gout is still frequently managed sub-optimally, even in the hospital and primary care settings. Gout should be considered a major disease since it can potentially lead to multiple disabilities from joint destruction, nephropathy and increased cardiovascular morbidity and mortality. The objectives of this review are to summarise the latest updated information and management of gout in the primary care setting.

Although several epidemiologic studies have shown the association between gout and cardiovascular outcomes, specific risk factors for developing cardiovascular diseases in Asian patients with gout are undisclosed. Thus, the purpose of this study was to investigate risks of cardiovascular outcomes and its related factors in Korean patients with gout. This retrospective clinical study used sampled cohort data from the National Health Insurance Service in Korea. Patients with gout were defined as subjects enlisted with an ICD-10 code (M10). Control patients were selected by frequency matching for age, sex, and index year. Primary outcomes included ischemic heart disease (IHD), congestive heart failure, cerebrovascular disease (CVD), or transient ischemic attack. We calculated the hazard ratio (HR) using Cox regression, adjusting potential confounders including age, sex, lifestyle habits, laboratory results, and medication. We identified 3306 patients with gout and an equal number of matched controls. Multivariate Cox regression analysis showed that gout patients had increased risks of IHD (HR: 1.860, 95% CI: 1.446–2.392), acute myocardial infarction (HR: 3.246, 95% CI: 1.460–7.217), and CVD (HR: 1.552, 95% CI: 1.177–2.036). Old age, current smoking, frequent alcohol intake, high low-density lipoprotein, and diabetes mellitus increased the risk of cardiovascular outcomes, yet hypouricemic agents decreased the risk of cerebrovascular diseases. Our data corroborate that it is crucial to identify and manage traditional cardiovascular risk factors alongside lowering urate levels in patients with gout. [ABSTRACT FROM AUTHOR]

Background. Gout is frequently accompanied by hypertension, obesity, and/or impaired glucose tolerance, which are often complicated with heavy smoking and dietary violations, especially in male patients.Objective. To determine the behavioral characteristics of gout patients that could impact the results of urate lowering therapy.Subjects and methods. The relationship between behavioral characteristics and results of urate lowering therapy were investigated in 74 male gout patients of Chengdu Rheumatism Hospital. The results of treatment were evaluated using serum uric acid contents before and after treatment, VAS pain score before and after treatment. Behavioral characteristics for the last ten years (smoking status, daily volume of drinking water, etc.) were accessed by means of retrospective survey.Results. In gout patients with poor treatment response, serum uric acid at the beginning of the treatment was already significantly lower (365.76 ± 163.06 μmol/L); this trend was also noted in a “slow progress” group, while patients with higher serum uric acid before treatment had notably better response to urate lowering therapy. During further analysis age negatively correlated with serum uric acid (r = –0.328; p = 0.002) and uric acid clearance ratio (r = –0.299; p = 0.002).In patients with uric acid clearance ratio above 40 % the prevalence of kidney diseases (stones or dysfunction) was significantly lower compared to other groups. There was no significant influence of hypertension, diabetes mellitus, fatty liver or hyperlipidaemia on uric acid clearance ratio (p > 0.05).Amount of drinking water also influenced the serum uric acid clearance ratio. Bigger amount of patients in the “fast progress” group (40.0 % compared to 30.44 and 25.0 %) tended to drink more water.Conclusion. In most gout patients, serum uric acid levels before treatment acted as the reliable predictor of good response to urate lowering therapy. Treatment response (serum uric acid clearance ratio) correlated positively with the hyperuricemia and drinking sufficient amounts of water, negatively – with prolonged smoking (more than 10 years) and age.

The burden of hyperuricaemia has been steadily increasing both globally and in India. The increasing number of hyperuricaemiaassociated co-morbidities, such as Chronic Kidney Disease (CKD), Type 2 Diabetes Mellitus (T2DM), Cardiovascular Diseases (CVD), and hypertension, implies that hyperuricaemia is associated with an increased risk of other chronic conditions or diseases. Despite the availability of several guidelines on hyperuricaemia, recommendations for appropriate titration of Urate Lowering Therapy (ULT) to achieve and maintain appropriate serum Uric Acid (sUA) levels in the Indian context are unclear. Another important challenge is the diagnosis and management of asymptomatic hyperuricaemia with ULT. This review summarises evidence-based discussion and review of literature by expert panellists on hyperuricaemia management with ULT, particularly with Xanthine Oxidase (XO) inhibitors. Based on the discussion, the experts developed a dose-titration algorithm for initiation and long-term management of hyperuricaemia with ULT, comprising febuxostat. The review also highlights some of the current challenges in hyperuricaemia management, which when addressed would benefit primary care physicians across the country for early screening and timely management of hyperuricaemia. [ABSTRACT FROM AUTHOR]

The burden of hyperuricaemia has been steadily increasing both globally and in India. The increasing number of hyperuricaemia-associated co-morbidities, such as Chronic Kidney Disease (CKD), Type 2 Diabetes Mellitus (T2DM), Cardiovascular Diseases (CVD), and hypertension, implies that hyperuricaemia is associated with an increased risk of other chronic conditions or diseases. Despite the availability of several guidelines on hyperuricaemia, recommendations for appropriate titration of Urate Lowering Therapy (ULT) to achieve and maintain appropriate serum Uric Acid (sUA) levels in the Indian context are unclear. Another important challenge is the diagnosis and management of asymptomatic hyperuricaemia with ULT. This review summarises evidence-based discussion and review of literature by expert panellists on hyperuricaemia management with ULT, particularly with Xanthine Oxidase (XO) inhibitors. Based on the discussion, the experts developed a dose-titration algorithm for initiation and long-term management of hyperuricaemia with ULT, comprising febuxostat. The review also highlights some of the current challenges in hyperuricaemia management, which when addressed would benefit primary care physicians across the country for early screening and timely management of hyperuricaemia.

Although several epidemiologic studies have shown the association between gout and cardiovascular outcomes, specific risk factors for developing cardiovascular diseases in Asian patients with gout are undisclosed. Thus, the purpose of this study was to investigate risks of cardiovascular outcomes and its related factors in Korean patients with gout. This retrospective clinical study used sampled cohort data from the National Health Insurance Service in Korea. Patients with gout were defined as subjects enlisted with an ICD-10 code (M10). Control patients were selected by frequency matching for age, sex, and index year. Primary outcomes included ischemic heart disease (IHD), congestive heart failure, cerebrovascular disease (CVD), or transient ischemic attack. We calculated the hazard ratio (HR) using Cox regression, adjusting potential confounders including age, sex, lifestyle habits, laboratory results, and medication. We identified 3306 patients with gout and an equal number of matched controls. Multivariate Cox regression analysis showed that gout patients had increased risks of IHD (HR: 1.860, 95% CI: 1.446–2.392), acute myocardial infarction (HR: 3.246, 95% CI: 1.460–7.217), and CVD (HR: 1.552, 95% CI: 1.177–2.036). Old age, current smoking, frequent alcohol intake, high low-density lipoprotein, and diabetes mellitus increased the risk of cardiovascular outcomes, yet hypouricemic agents decreased the risk of cerebrovascular diseases. Our data corroborate that it is crucial to identify and manage traditional cardiovascular risk factors alongside lowering urate levels in patients with gout.

Objectives: To determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.Methods: We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.Results: We included 79 gouty patients [mean (±SD) age 61.8±14 years, 91% males, median disease duration 4 (IQR 1.5;10) years]. Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥50% at M6 was more frequent without than with relapse (54% vs. 26%, P=0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse [AUC 0.649 (95% confidence interval 0.488; 0.809)]. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 [OR 3.35 (95% confidence interval 0.98; 11.44)].Conclusion: A high reduction in US tophus size is associated with lower probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: To develop French Society of Rheumatology-endorsed recommendations for the management of urate-lowering therapy (ULT).Methods: Evidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and two Delphi rounds to finalize them.Results: A set of 3 overarching principles and 5 recommendations was elaborated. The overarching principles emphasize the importance of patient education, especially the need for explaining the objective of lowering serum urate (SU) level to obtain crystal dissolution, clinical symptoms disappearance and avoidance of complications. ULT is indicated as soon as the diagnosis of gout is established. SU level must be decreased below 300μmol/l (50mg/l) in all gout patients or at least below 360μmol/l (60ml/l) when the 300μmol/l target cannot be reached, and must be maintained at these targets and monitored life-long. The choice of the ULT primarily relies on renal function: in patients whose estimated glomerular filtration rate (eGFR) is above 60ml/min/1.73m2, first-line ULT is allopurinol; in those with eGFR between 30 and 60ml/min/1.73m2, allopurinol use must be cautious and febuxostat can be considered as an alternative; and in those whose eGFR is below 30ml/min/1.73m2, allopurinol must be avoided and febuxostat should be preferred. Prophylaxis of ULT-induced gout flares involves progressive increase of ULT dosage and low-dose colchicine for at least 6 months. Cardiovascular risk factors and diseases, the metabolic syndrome and chronic kidney disease must be screened and managed.Conclusion: These recommendations aim to provide simple and clear guidance for the management of ULT in France. [ABSTRACT FROM AUTHOR]

Objectives: Gout is an independent cardiovascular (CV) risk factor with significant morbidity and mortality. We aimed to estimate the prevalence of gout, characteristics and management in a hospitalized population for CV disease, a topic that remains to be defined.Methods: An observational, descriptive, cross-sectional study was carried out in patients admitted for CV events in the Cardiology, Neurology, and Vascular Surgery units of a tertiary center. Patients were selected following a non-consecutive, systematic sampling. Data about CV disease and gout were obtained from face-to-face interviews and patients' records. Gout diagnosis was established using the 2015 ACR/EULAR clinical classification criteria. The registration rate of gout was assessed by auditing patients' records and hospital discharge reports of CV events from the units of interest in the previous 2 years. To predict the presence of gout, multivariate logistic regression models were built to study the possible explanatory variables.Results: Two hundred and sixty six participants were recruited, predominantly males (69.9%) and Caucasians (96.6%) with a mean age of 68 years. Gout was identified in 40 individuals; thus, the prevalence was 15.0% (95% CI 10.9–19.2%). In 35% of cases, the diagnosis was absent from patients' records. Gout was found in 1.4–2.6% of hospital discharge reports of CV events, also indicating under-registration. The disease was long-standing, but with low reported rates of flares, involved joints, and tophi. At admission, only half of the gout patients were on urate-lowering therapy, being 38.5% of them on serum urate

BACKGROUND Gout is the most common form of inflammatory arthritis worldwide and its prevalence is rising. In Switzerland, there are no data available on the characteristics and treatment of gout patients. In this study, we aimed to describe numbers of patients affected by gout and hyperuricaemia and unveil approaches Swiss primary care physicians (PCPs) use for the management. METHODS This was a retrospective observational study using electronic medical routine data provided from 242 Swiss PCPs. Included were all their patients receiving urate-lowering therapy (ULT), with a diagnostic code for gout or who had a serum uric acid (SUA) measurement. According to their disease status, patients were classified into four subgroups (normal urate, hyperuricaemia, untreated gout, treated gout). For treatment analysis, patients with SUA measurements before and after ULT initiation were included. Comorbidities and risk factors for secondary causes relevant in the context of gout were collected. Outcomes were prevalence of gout and hyperuricaemia, characteristics of patients according to subgroup, number of SUA measurements, levels of SUA and patients who reached the treatment goal of a SUA level

The definition and management of asymptomatic hyperuricemia has been an area of controversy for many decades. Debate persists regarding the benefit of treating all cases of asymptomatic hyperuricemia and hence, unsurprisingly there are no clear clinical practice guidelines from our country. Ten members consisting of eminent physicians, endocrinologists, nephrologist and a rheumatologist were selected by the Integrated Diabetes & Endocrine Academy (IDEA) for a closed meeting with the aim to come to a consensus. A literature search was performed using PubMed and Cochrane library following which published articles in indexed peer review journals were selected. Each participant voiced their opinion after reviewing the available data and a consensus was reached after three meetings by voting. Recommendations were made on important areas such as definition, investigation and management of asymptomatic hyperuricemia. • There are no clear clinical practice guidelines on management of asymptomatic hyperuricemia from India. • Unnecessary investigation of serum uric acid for all patients with rheumatological symptoms should be discouraged. • Urate lowering therapy are well known for its side effects however, new evidence showing benefit of therapy cannot be ignored. • This consensus statement aims to lay down clear recommendations in the management of asymptomatic hyperuricemia. [ABSTRACT FROM AUTHOR]

Thanda Aung,* Gihyun Myung,* John D FitzGerald Division of Rheumatology/Department of Internal Medicine, University of California, Los Angeles, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Gout is the most common inflammatory arthritis characterized by painful disabling acute attacks. It is caused by hyperuricemia and deposition of urate crystals in and around the joints. Long-standing untreated hyperuricemia can lead to chronic arthritis with joint damage, tophi formation and urate nephropathy. Gout is associated with significant morbidity and health care associated cost. The goal of long-term therapy is to lower the serum urate level to promote dissolution of urate crystals, reduce recurrent acute gout flares, resolve tophi and prevent joint damage. Despite the presence of established gout treatment guidelines and effective medications to manage gout, patient outcomes are often poor. Etiology for these shortcomings is multifactorial including both physician and patient characteristics. Poor adherence to urate-lowering therapy (ULT) is prevalent and is a significant contributor to poor patient outcomes. This article reviews the treatment strategies for the management of hyperuricemia in chronic gout, gaps in quality of care in gout management, factors contributing to poor adherence to ULT and discusses potential interventions to achieve improved gout-related outcomes. These interventions include initiation of prophylactic anti-inflammatory medication when starting ULT, frequent follow-ups, regular serum urate monitoring and improved patient education, which can be achieved through pharmacist- or nurse-assisted programs. Interventions such as these could improve adherence to ULT and, ultimately, result in optimal gout-related outcomes. Keywords: gout, adherence, urate-lowering therapy

CSL Tan,1 GG Teng,1,2 KJ Chong,2 PP Cheung,1,2 AYN Lim,1,2 HL Wee,3,4 A Santosa1,2 1University Medicine Cluster, Division of Rheumatology, National University Health System, 2Department of Medicine, Yong Loo Lin School of Medicine, 3Department of Pharmacy, Faculty of Science, 4Saw Swee Hock School of Public Health, National University of Singapore, Singapore Background: The outcomes of any chronic illness often depend on patients’ adherence with their treatment. A tool is lacking to assess adherence in gout that is standardized, allows real-time feedback, and is easy to understand.Objective: We set out to evaluate the utility of the 8-item Morisky Medication Adherence Scale (MMAS-8) in monitoring medication adherence in a multiethnic Asian gout cohort on urate-lowering therapy (ULT).Methods: This cohort study recruited patients with gout where baseline and 6-monthly clinical data, self-report of adherence, and health status by Gout Impact Scale (GIS) and EuroQoL-5 dimension 3 levels were collected. Those who received at least 9 months of ULT were analyzed. Convergent and construct validities of MMAS-8 were evaluated against medication possession ratio (MPR) and known groups, clinical outcomes, and patient-reported outcomes. Internal consistency and test–retest reliability were assessed using Cronbach’s alpha and intraclass correlation coefficient (ICC), respectively.Results: Of 91 patients, 92.3% were male, 72.5% Chinese with mean age 53.5 years. MMAS-8 (mean 6.17) and MPR (mean 96.3%) were poorly correlated (r=0.069, P=0.521). MMAS-8 did not differ between those who did or did not achieve target serum urate (SU)

Objectives We aimed to determine the ability of ultrasonography (US) to show disappearance of urate deposits in gouty patients requiring urate-lowering therapy (ULT). Methods We performed a 6-month multicentre prospective study including patients with: proven gout; presence of US features of gout (tophus and/or double contour sign) at the knee and/or first metatarsophalangeal joints; and no current ULT. US evaluations were performed at baseline and at months 3 and 6 (M3, M6) after starting ULT. Outcomes were: the change in US features of gout at M6 according to final (M6) serum urate (SU) level (high, > 360 μmol/l, i.e. > 6 mg/dl; low, 300–360 μmol/l, i.e. 5-6 mg/dl; very low, < 300 μmol/l, i.e. < 5 mg/dl); and correlation between changed US features and final SU level. Results We included 79 gouty patients (mean ± s. d. age 61.8 (14) years, 91% males, disease duration 6.3 (6.1) years). Baseline SU level was 530 ± 97 µmol/l (i.e. 8.9 mg/dl ± 1.6mg/dl). At least one US tophus and double contour sign was observed in 74 (94%) and 68 (86%) patients, respectively. Among the 67 completers at M6, 18 and 39 achieved a very low and low SU level, respectively. We found a significant decrease in US features of gout among patients with the lowest SU level (P < 0.001). Final M6 SU level was positively correlated with decreased size of tophus (r = 0.54 [95% CI: 0.34, 0.70], P < 0.0001), and inversely correlated with proportion of double contour sign disappearance (r=−0.59 [−0.74, −0.40]). Conclusion US can show decreased urate deposition after ULT, which is correlated with decreased SU level. The responsiveness of US in gout is demonstrated and can be useful for gout follow-up and adherence to ULT. [ABSTRACT FROM AUTHOR]

Gout is an inflammatory musculoskeletal disorder with a prevalence of 1.6–6.8% in Australia. Gout is characterised by acute attacks of severe joint pain secondary to raised serum concentrations of uric acid and joint deposits of monosodium urate crystals. Recurrent attacks can affect quality of life and lead to irreversible joint damage. The prevalence of gout is increased in older people, and age‐related renal impairment, altered drug distribution and increased prevalence of comorbidities have significant consequences for safe and effective gout pharmacotherapy. For treatment of acute attacks in older people, dose reduction of colchicine may be needed due to renal impairment, and potential drug interactions require consideration. Use of non‐steroidal anti‐inflammatory drugs is limited by peptic ulceration, ischaemic heart disease, hypertension and renal impairment. Short courses of oral glucocorticoids may be preferable. For long‐term urate‐lowering therapy, allopurinol, probenecid and febuxostat are available in Australia. Lower starting doses of allopurinol are recommended in patients with renal impairment, but dose escalation to achieve target urate should follow. Concerns regarding increased cardiovascular risk with febuxostat are relevant to older patients. Despite the availability of effective therapy, gout remains undertreated, with maintenance of urate‐lowering therapy a major challenge. Education of patients and health professionals is essential to improve adherence to therapy. [ABSTRACT FROM AUTHOR]

Background Gout patients do not routinely achieve optimal outcomes related in part to suboptimal administration of urate lowering therapy (ULT) including first-line xanthine oxidase inhibitors allopurinol or febuxostat. Studies leading to the approval of febuxostat compared this agent to allopurinol in inappropriately low, fixed doses. We will compare allopurinol with febuxostat in gout using appropriately titrated doses of both agents and a “treat-to-target” strategy congruent with specialty guidelines. Methods We have planned and initiated the Veterans Affairs (VA) Cooperative Study Program (CSP) 594, Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study. This large double-blind, non-inferiority trial will enroll 950 gout patients randomized to receive allopurinol or febuxostat. Patients will be followed for a total of 72 weeks encompassing 3 distinct 24-week study phases. During Phase I (0–24 weeks), participants will undergo gradual dose titration of ULT until achievement of serum uric acid (sUA) <6.0 mg/dL or <5.0 mg/dL if tophi are present. Dose escalation will not be allowed during final three study visits of Phase 2 (24–48 weeks) and during Phase 3 (48–72 weeks). The primary study outcome is the proportion of participants experiencing at least one gout flare during Phase 3. Subsequent to the 72-week study, participants will be followed passively for up to 10 years after the study to assess long-term health outcomes. Conclusion With its completion, the VA Comparative Effectiveness in Gout: Allopurinol vs Febuxostat study will demonstrate the central role of gradual ULT dose escalation and a treat-to-target strategy in gout management. [ABSTRACT FROM AUTHOR]

Objective In the management of chronic gout, a large proportion of patients need long-term management with urate lowering therapy (ULT). This study reviews medication adherence to ULT and summarizes factors associated with adherence. Methods We performed a systematic literature search for studies on adherence to ULT among gout patients in PubMed, Embase, CINAHL, and PsycINFO. We conducted meta-analysis, with a random effect model, for the studies reporting the proportion of patients considered adherent to at least 80% of prescribed medication or time taken. We explored potential sources of heterogeneity, including geographic area and measure of adherence. Narrative summaries were made for data on adherence assessed/defined by Medication Event Monitoring System (MEMS)/pill-count or patient-reported, occurrence of a gap in therapy ≥30 days (non-persistence), and factors associated with adherence. Results Of the 24 studies, 16 assessed adherence using prescription/claims data, two by the MEMS or pill count, and six by patient-reported data. The pooled proportion of adherent patients ( n = 13) was 46% (95% CI: 41–51); 45% across studies conducted in the USA (n = 8) and 48% in other countries ( n = 5). Adherence assessed by MEMS/pill count and patient-reported was much higher than by studies using prescription/claims data. Non-persistence ( n = 6) ranged from 54% to 87%. Factors associated with adherence were investigated in 18 studies. Strong evidence for a positive association with older age, more comorbidities, and the presence of diabetes or hypertension was found. Conclusion Medication adherence to ULT among gout patients was poor. Better insight into reasons and consequences or poor adherence is needed. [ABSTRACT FROM AUTHOR]

If hyperuricemia is an independent risk factor in blood-pressure control, urate-lowering therapy should be used to reduce cardiovascular risk. It may also act as a prognostic marker of other abnormalities. This review presents current evidence on the relationship between hyperuricemia and hypertension. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In patients with gout, serum uric acid (sUA) concentrations should be lowered at least below the target of 6 mg/dL (even below 5 mg/dL in patients with severe gout). To achieve this goal, urate lowering medications (ULMs) should be considered. Currently- used ULMs include xanthine-oxidase inhibitors such as allopurinol, febuxostat, as well as available uricosuric agents. However, evidence comparing these agents remains scant. We have conducted a systematic review and meta-analysis to retrieve evidence on the clinical trials on the above-mentioned drugs in the treatment of gout. MATERIALS AND METHODS: The following efficacy outcomes were considered in the metaanalysis: (1)% of patients meeting the therapeutic target for sUA level (<6 mg/dl) and (2) percentage reduction in sUA concentration at the end of the study compared with baseline values. An explorative analysis on safety was also conducted. RESULTS: In total, 16 papers concerned febuxostat, 15 allopurinol, 4 benzbromarone and none involved probenecid. Overall, 70.7% of patients reached the target of sUA with febuxostat therapy; the reduction in sUA was 45.3%. Corresponding figures with allopurinol were 44.4% and 33.8%, respectively. The number of patients on benzbromarone (N=129) was too low to retrieve definitive findings. The advantage for febuxostat over allopurinol was evident also in patients with renal dysfunction. Safety analysis favored febuxostat over allopurinol (OR 0.85; 95% CI: 0.75-0.97). CONCLUSIONS: On the basis of the reported data, febuxostat can play a major role in the treatment of hyperuricaemia and gout. Febuxostat is a suitable pharmacological option for first line treatment of gout, given its established efficacy and safety, documented in a high number of clinical studies and in daily practice. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia may contribute to renal injury. We do not know whether use of treatments that lower urate reduce the progression of chronic kidney disease (CKD) and cardiovascular disease. We performed a systematic review and meta-analysis of randomized controlled trials to assess the benefits and risks of treatments that lower urate in patients with stages 3-5 CKD. Methods: We searched MEDLINE, EMBASE, CENTRAL, Web of Science and trial registers for randomized controlled trials (RCTs) without language restriction. Two authors independently screened articles, assessed risk of bias and extracted data. Data obtained included serum uric acid, serum creatinine or other estimates of glomerular filtration rate, incidence of end-stage renal disease (ESRD), systolic and diastolic blood pressure, proteinuria, cardiovascular disease and adverse events. Results: From the 5497 citations screened, 19 RCTs enrolling 992 participants met our inclusion criteria. Given significant heterogeneity in duration of follow-up and study comparators, only trials greater than 3 months comparing allopurinol and inactive control were meta-analyzed using random effects models. Pooled estimate for eGFR was in favour of allopurinol with a mean difference (MD) of 3.2 ml/min/1.73 m2, 95% CI 0.16-6.2 ml/min/1.73 m2, p=0.039 and this was consistent with results for serum creatinine. Statistically significant reductions in serum uric acid, systolic and diastolic blood pressure were found, favouring allopurinol. There were insufficient data on adverse events, incidence of ESRD and cardiovascular disease for analysis. Conclusions: Adequately powered RCTs are needed to establish whether treatments that lower urate have beneficial renal and cardiovascular effects. [ABSTRACT FROM AUTHOR]

Gout is a commonly treated inflammatory arthritis that is often managed in the primary care setting. This disease is prevalent among the multi-ethnic Malaysian population. Unfortunately, gout is still frequently managed sub-optimally, even in the hospital and primary care settings. Gout should be considered a major disease since it can potentially lead to multiple disabilities from joint destruction, nephropathy and increased cardiovascular morbidity and mortality. The objectives of this review are to summarise the latest updated information and management of gout in the primary care setting., (© Academy of Family Physicians of Malaysia.)

Introduction: There has been a resurgence in gout therapeutics in the last decade, not only for the management of gout flares, but also for the treatment of hyperuricemia. This editorial summarizes new, emerging therapies for people with gout. Areas covered: We review several new therapies for gout, including those that are focused on lowering serum urate (levotofisopam, ulodesine, verinurad, merbarone, KUX-1151, UR-1102, FYU-981, SEL-212), or treating gout flares (canakinumab, bucillamine) or both (arhalofenate, diacerein). Expert opinion: Among therapies with both urate lowering and anti-inflammatory action, arhalofenate seems promising, but more data are needed. Examining therapies aimed at treating gout flares [anti-inflammatory action], bucillamine has some potential, but more data and Phase III studies are needed, to better understand its efficacy and safety. Among the urate-lowering therapies (ULTs), verinurad seems to be the most promising, while levotofisopam and ulodesine require more data. A uricase-replacement therapy with improved immune reaction (SLE-212) is in a Phase II trial. A number of ULTs including KUX-1151, UR-1102 and FYU-981 are in early development and more will be known once initial data and studies are published.

Background and Objectives: Higher serum uric acid levels, even within the reference range, are strongly associated with increased activity of the renin-angiotensin system (RAS) and risk of incident hypertension. However, the effect of lowering serum uric acid on RAS activity in humans is unknown, although the data that lowering serum uric acid can reduce BP are conflicting., Design, Setting, Participants, & Measurements: In a double-blind placebo-controlled trial conducted from 2011 to 2015, we randomly assigned 149 overweight or obese adults with serum uric acid ≥5.0 mg/dl to uric acid lowering with either probenecid or allopurinol, or to placebo. The primary endpoints were kidney-specific and systemic RAS activity. Secondary endpoints included mean 24-hour systolic BP, mean awake and asleep BP, and nocturnal dipping., Results: Allopurinol and probenecid markedly lowered serum uric acid after 4 and 8 weeks compared with placebo (mean serum uric acid in allopurinol, probenecid, and placebo at 8 weeks was 2.9, 3.5, and 5.6 mg/dl, respectively). The change in kidney-specific RAS activity, measured as change in the median (interquartile range) renal plasma flow response to captopril (in ml/min per 1.73 m 2 ) from baseline to 8 weeks, was -4 (-25 to 32) in the probenecid group ( P =0.83), -4 (-16 to 9) in the allopurinol group ( P =0.32), and 1 (-21 to 17) in the placebo group ( P =0.96), with no significant treatment effect ( P =0.77). Similarly, plasma renin activity and plasma angiotensin II levels did not significantly change with treatment. The change in mean (±SD) 24-hour systolic BPs from baseline to 8 weeks was -1.6±10.1 with probenecid ( P =0.43), -0.4±6.1 with allopurinol ( P =0.76), and 0.5±6.0 with placebo ( P =0.65); there was no significant treatment effect ( P =0.58). Adverse events occurred in 9%, 12%, and 2% of those given probenecid, allopurinol, or placebo, respectively., Conclusions: In contrast to animal experiments and observational studies, this randomized, placebo-controlled trial found that uric acid lowering had no effect on kidney-specific or systemic RAS activity after 8 weeks or on mean systolic BP. These data do not support the hypothesis that higher levels of uric acid are a reversible risk factor for increased BP., (Copyright © 2017 by the American Society of Nephrology.)

Evidence is accumulating indicating a role for uric acid in the genesis and progression of kidney disease, and a few studies are beginning to show a possible beneficial effect of urate-lowering therapy. Whether this holds true for renal allograft recipients is not clear. In this short review evidence from epidemiological as well as intervention studies is summarized and discussed, with some practical considerations presented at the end.