Urate-lowering Medications Research Articles

The clinical characteristics, diagnosis and treatment of patients with gout in China

Objective: To investigate the demographic characteristics, clinical features, diagnosis and treatment of patients with gout in China. Methods: Clinical data of 6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or autonomous regions in China were collected and analyzed. Results: (1) The ratio of male to female in patients with gout was 14.7∶1. The mean age of onset was (48.8±15.1) years old. Mean serum urate level was (526.7±132.3) μmol/L. Patients' education background was of U-shaped distribution; (2) Hypertension was the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity [51.9%(3 536/6 814)]; (3) Alcohol and high-purine food intake were dominant triggering factors in men. The diagnosis of gout was made after onset in majority of patients with cardinal symptom arthralgia. Most patients had the disease less than 5 years, and the longer the course, the more flares in the previous year of entry; (4) Febuxostat was the mostly used urate-lowering medication. 20.7%(1 412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in 4 weeks, 12 weeks and 24 weeks after registration, and 18.9%(267/1 412), 29.1%(215/739) and 38.1%(101/265) of them reached the control target of serum urate levels, respectively. After treatment, patients' liver function was not affected, but serum creatinine levels decreased significantly. Conclusions: The proportion of gout patients who reach target serum urate level is very low. Further steps including education and survey need to be carried on.

Improvement in Diagnosis and Treat-to-Target Management of Hyperuricemia in Gout: Results from the GEMA-2 Transversal Study on Practice.

The objective of the study was to evaluate changes regarding main European League Against Rheumatism (EULAR) recommendations on diagnosis and treatment of gout compared to a previous assessment. The GEMA-2 (Gout Evaluation and MAnagement) is a transversal assessment of practice for gout by rheumatologists. Main outcome variables were improvement of the previous GEMA assessment regarding the rate of crystal-proven diagnosis and that reaching therapeutic serum urate target below 6mg/dl at last visit. Other management variables (prophylaxis, treatment of flares, lifestyle change advice) were also evaluated along with general characteristics. The sample was powered to include at least 483 patients for up to 50% change. Data on management of 506 patients were retrieved from 38 out of 41 rheumatology units that participated in the previous GEMA audit. Crystal-proved diagnosis rate increased from 26% to 32% (31% improvement) and was higher in gout-dedicated practices; ultrasonography contributed to diagnosis in less than 1% of cases. Therapeutic serum urate at last visit improved from 41% to 64% of all patients (66% of patients on urate-lowering medications), in any case over 50% improvement from the previous assessment. The use of any urate-lowering medication available was not prescribed as per label dosing in patients who failed to achieve target serum urate. Clinical inertia to increase doses of either allopurinol or febuxostat was still present in clinical practice. Over 50% improvement in targeting therapeutic serum urate has been observed, but clinical inertia is still present. Diagnosis is still mostly clinically based, ultrasonography not being commonly contributive. Menarini España.

Physical exercises and weight loss in obese patients help to improve uric acid.

Objectiveto assess the impact of longitudinal change of the overweight and physical activity on hyperuricemia.MethodsWe performed a retrospective cohort study. Demographic information, clinical features, laboratory findings, body weight and physical exercises pattern were documented.ResultsAltogether 4678 cases of hyperuricemia were enrolled. The median aged males were most affected. Individuals in the middle age had the highest prevalence of being overweight (2501/3382, 74.0%). Middle aged with BMI≥25 kg/m2 were more likely to lose weight (963/2807, 34.3%). BMI and waist circumference control helped to reduce serum uric acid. Overweight population was more likely to use urate-lowering or uricosuric medication (3025/3382, 89.4%). Intermediate and heavy activity were associated with bigger SUA improvement. Patients in the age of 35-60 were more likely to do physical exercises than the others.ConclusionBeing overweight is strongly associated with hyperuricemia. Successful weight control was correlated with significant uric acid reduction. Intermediate to heavy physical activity helps to reduce waist circumference and SUA. In the hyperuricemia population, obese, middle aged men were the most affected, and also the most likely to do more exercises and get their bodyweight back to normal.

Early onset hyperuricemia is a prognostic marker for kidney graft failure: Propensity score matching analysis in a Korean multicenter cohort.

It remains inconclusive whether hyperuricemia is a true risk factor for kidney graft failure. In the current study, we investigated the association of hyperuricemia and graft outcome. We performed a multi-center cohort study that included 2620 kidney transplant recipients. The patients were classified as either normouricemic or hyperuricemic at 3 months after transplantation. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females or based on the use of urate-lowering medications. The two groups were compared before and after propensity score matching. A total of 657 (25.1%) patients were classified as hyperuricemic. The proportion of hyperuricemic patients increased over time, reaching 44.2% of the total cohort at 5 years after transplantation. Estimated glomerular filtration rate and donor type were independently associated with hyperuricemia. Hyperuricemia was associated with graft loss according to multiple Cox regression analysis before propensity score matching (hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.14–2.13, P = 0.005) as well as after matching (HR = 1.65, 95% CI = 1.13–2.42, p = 0.010). Cox regression models using time-varying hyperuricemia or marginal structural models adjusted with time-varying eGFR also demonstrated significant hazards of hyperuricemia for graft loss. Cardiovascular events and recipient survival were not associated with hyperuricemia. Overall, hyperuricemia, especially early onset after transplantation, showed an increased risk for graft failure. Further studies are warranted to determine whether lowering serum uric acid levels would be beneficial to graft survival.

Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine

BackgroundHyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. Patients and MethodsFrom December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. ResultsOne patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. ConclusionCombination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

Febuxostat for the chronic management of hyperuricemia in patients with gout

ABSTRACTFebuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR), and a major alternative to the scarce number of urate-lowering medications available in the last decades. Its inhibition of XOR is more potent than allopurinol in a mg to mg comparison, what is associated to achievement of serum urate target more frequently than allopurinol at doses tested in clinical trials, especially in patients with the highest baseline serum urate levels. Its pharmacokinetics is not greatly dependent on renal clearance, contrary to allopurinol, what may be an advantage in patients with chronic kidney disease. Several trials are further evaluating both the cardiovascular safety of febuxostat and its possible beneficial effect on renal function preservation. Still scarce, but clinically interesting, evidence on its use in transplant patients has been recently released.

Association of Visceral Fat and Liver Fat With Hyperuricemia.

To examine cross-sectionally whether intraabdominal fat area (IAFA), i.e., visceral fat, and liver fat assessed by computed tomography (CT) are independently associated with hyperuricemia. Subjects were 801 Japanese men not taking antidiabetic, antihypertensive, or urate-lowering medications, without any history of renal disease, cardiovascular disease, or cancer, and with serum creatinine <1.5 mg/dl. Abdominal, thoracic, and thigh fat areas were measured by CT. Total fat area (TFA) was the sum of these fat areas. Total subcutaneous fat area (TSFA) was TFA minus IAFA. Liver fat was assessed by liver-to-spleen (L/S) ratio measured by CT. Hyperuricemia was defined as serum uric acid level >7.0 mg/dl. Its association with adiposity was tested using logistic regression. The prevalence of hyperuricemia was 19.6% (157 men). Both greater IAFA and lower L/S ratio were independently associated with hyperuricemia in models that simultaneously included IAFA and L/S ratio: multiple-adjusted odds ratios of hyperuricemia for quintiles 3, 4, and 5 of IAFA were 2.16 (95% confidence interval [95% CI] 1.02-4.59), 2.41 (95% CI 1.13-5.16), and 4.00 (95% CI 1.81-8.85), respectively, compared to quintile 1, and the L/S ratios for quintiles 3, 2, and 1 were 2.34 (95% CI 1.16-4.75), 2.15 (95% CI 1.06-4.34), and 2.79 (95% CI 1.35-5.76), respectively, compared to quintile 5. Both IAFA and L/S ratio remained significant even after adjusting for abdominal subcutaneous fat area, TFA, TSFA, body mass index, or waist circumference. Of all fat measurements, IAFA had the strongest association with hyperuricemia by Akaike's information criteria. Greater amounts of both visceral fat and liver fat were independently associated with hyperuricemia.

Dual-Energy CT in Patients with Suspected Gouty Arthritis:: Effects on Treatment Regimen and Clinical Outcome

This investigation aimed to evaluate the impact on treatment regimen and clinical outcome of dual-energy computed tomography (DECT) in patients with suspected gouty arthritis. We retrospectively analyzed electronic medical records (EMR) of 39 patients (36 male, 3 female; age range, 36-85 years) who underwent DECT of peripheral joints because of suspected gouty arthritis. We assessed the prior medical history, lab results, treatment regimen, and medications before and after DECT, and changes in subjective severity of symptoms as stated by patients in the EMR. The presence of monosodium urate (MSU) crystals in the index joint was verified with DECT. Several patients had a prior diagnosis of gout (n = 9), hyperuricemia (n = 6), rheumatoid arthritis (n = 3), or psoriatic arthritis (n = 3). Elevated uric acid blood levels were detected in 32 patients (82%) before DECT. On DECT, MSU crystals were detected in 23 patients (59%). Of the 36 cases, the current treatment regimen was modified after DECT to gout-specific therapy in 22 cases and other rheumatic diseases were targeted in 14 cases. Several medications were prescribed more frequently based after DECT compared to before DECT imaging, including steroids (n = 20 vs. n = 12, respectively), colchicine (n = 13 vs. n = 4, respectively), and urate-lowering medication (n = 18 vs. n = 11, respectively). A subjective reduction of clinical symptoms during cumulative follow-up was reported by 34 patients (87.2%). Both positive and negative findings of MSU crystals on DECT have a significant impact on the treatment regimen and clinical outcome of patients with suspected gouty arthritis and facilitate differentiation from other rheumatic diseases.

SAT0509 Factors Associated to the Development of Tophi in Patients with Gout

Backgrounddevelopment of tophi has been associated with increasing level of serum urate (Gutman AB, A&R 1973), whereas other factors have not been clearly stated, such as gender, comorbidities or concomitant...

Efficacy and Safety of Febuxostat, a Novel Nonpurine Selective Inhibitor of Xanthine Oxidase for the Treatment of Hyperuricemia in Kidney Transplant Recipients

BackgroundFebuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia. In this study, we evaluated the efficacy and safety of febuxostat for the management of hyperuricemia in renal transplant recipients. Patients and methodsBetween June 2012 and January 2013, a total of 22 renal transplant recipients (56 ± 10 years old) with hyperuricemia were enrolled in this study. All patients underwent de novo kidney transplantation, except for 1 patient, who received a second kidney transplant. Ten patients receiving allopurinol and 3 patients receiving benzbromarone were converted to febuxostat at doses of 10–20 mg/d. In the remaining 9 patients, who did not have a history of other urate-lowering medications, febuxostat was initiated at a dose of 10 mg/d. ResultsUric acid levels after initiation of febuxostat were significantly lower than before treatment (5.7 ± 0.7 mg/mL vs 8.0 ± 0.8 mg/mL; P < .001). At last follow-up visit, 16 of the 22 patients (73%) achieved uric acid levels of ≤6.0 mg/dL, despite the low dosage of febuxostat. All patients were maintained on febuxostat without serious adverse events, except for 1 patient, who discontinued febuxostat because of numbness in the arms. ConclusionsLow-dose febuxostat is a promising alternative to allopurinol or benzbromarone for the treatment of hyperuricemia in kidney transplant recipients. The long-term urate-lowering efficacy and safety of febuxostat with regard to renal function in kidney transplant recipients with hyperuricemia requires further investigation.

Metabolite profiling reveals new insights into the regulation of serum urate in humans

Serum urate, the final breakdown product of purine metabolism, is causally involved in the pathogenesis of gout, and implicated in cardiovascular disease and type 2 diabetes. Serum urate levels highly differ between men and women; however the underlying biological processes in its regulation are still not completely understood and are assumed to result from a complex interplay between genetic, environmental and lifestyle factors. In order to describe the metabolic vicinity of serum urate, we analyzed 355 metabolites in 1,764 individuals of the population-based KORA F4 study and constructed a metabolite network around serum urate using Gaussian Graphical Modeling in a hypothesis-free approach. We subsequently investigated the effect of sex and urate lowering medication on all 38 metabolites assigned to the network. Within the resulting network three main clusters could be detected around urate, including the well-known pathway of purine metabolism, as well as several dipeptides, a group of essential amino acids, and a group of steroids. Of the 38 assigned metabolites, 25 showed strong differences between sexes. Association with uricostatic medication intake was not only confined to purine metabolism but seen for seven metabolites within the network. Our findings highlight pathways that are important in the regulation of serum urate and suggest that dipeptides, amino acids, and steroid hormones are playing a role in its regulation. The findings might have an impact on the development of specific targets in the treatment and prevention of hyperuricemia.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-013-0565-2) contains supplementary material, which is available to authorized users.

SAT0376 Uric Acid Levels as a Biomarker of Efficacy and Safety in Patients Treated with Pegloticase: Lessons Learned from us Clinical Experience

BackgroundPegloticase is a recombinant uricase recently approved in the EU for the treatment of severe, debilitating chronic tophaceous gout refractory to xanthine oxidase inhibitors (XOIs) or when XOIs are contraindicated....

FRI0391 Musculoskeletal high resolution ultrasonography assessment in real life outpatients with GOUT

BackgroundThe musculoskeletal high resolution ultrasonography (HRU) is useful in the gout diagnosis, the assessment of UMS deposits extension and following up the response to urate lowering therapy.Therefore we consider that...

New developments in gout

Gout is the most common type of inflammatory arthritis. This review summarizes the most recent studies on newer therapeutics, disease management strategies and treatment recommendations. There are several new therapeutic agents being investigated both for the management of the acute gout symptoms, targeting interleukin-1β, as well as urate-lowering therapies including uricase and inhibitors of renal urate transporter proteins. Interventions led by pharmacists and nurses, which include patient education, lifestyle advice, monitoring and titration of urate-lowering medications have been implemented to improve gout management. Recently, the American College of Rheumatology has published guidelines for nonpharmacologic and pharmacologic therapeutic approaches for hyperuricemia and acute gouty arthritis. New therapeutic agents targeting the mechanism of inflammation (IL-1β) are under investigation. In addition, new urate-lowering medications to be used alone or in combination with allopurinol are undergoing rigorous evaluation to use for patients not responding to or unable to take current therapies. There is also increasing interest in redesigning clinical care to improve patient education, self-management training and urate-lowering medication titration. Although we await results of these investigations, the American College of Rheumatology treatment guidelines provide a framework for clinicians in order to provide optimal gout care.

Patients’ knowledge and beliefs concerning gout and its treatment: a population based study

BackgroundFor patients to effectively manage gout, they need to be aware of the impact of diet, alcohol use, and medications on their condition. We sought to examine patients’ knowledge and beliefs concerning gout and its treatment in order to identify barriers to optimal patient self-management.MethodsWe identified patients (≥18 years of age) cared for in the setting of a multispecialty group practice with documentation of at least one health care encounter associated with a gout diagnosis during the period 2008–2009 (n = 1346). Patients were sent a questionnaire assessing knowledge with regard to gout, beliefs about prescription medications used to treat gout, and trust in the physician. Administrative electronic health records were used to identify prescription drug use and health care utilization.ResultsTwo hundred and forty patients returned surveys out of the 500 contacted for participation. Most were male (80%), white (94%), and aged 65 and older (66%). Only 14 (6%) patients were treated by a rheumatologist. Only a minority of patients were aware of common foods known to trigger gout (e.g., seafood [23%], beef [22%], pork [7%], and beer [43%]). Of those receiving a urate-lowering medication, only 12% were aware of the short-term risks of worsening gout with initiation. These deficits were more common in those with active as compared to inactive gout.ConclusionKnowledge deficits about dietary triggers and chronic medications were common, but worse in those with active gout. More attention is needed on patient education on gout and self-management training.

Improving the Use of Allopurinol in Chronic Gout: Monitoring Oxypurinol Levels to Guide Therapy

Urate-lowering therapy (ULT), adjusted to achieve and maintain a serum uric acid (SUA) of <6mg/dl, remains the standard of care for the chronic management of gout. New urate-lowering medications are important options; however, these agents should be reserved for patients who do not tolerate or cannot achieve SUA <6mg/dl on allopurinol. The result of oxypurinol monitoring to guide allopurinol therapy suggests that allopurinol should still be considered first-line ULT for gout.

Pegloticase for chronic gout.

Pegloticase is a potential new treatment option for patients with chronic gout intolerant to other urate-lowering therapies. To assess safety (adverse events, death) and efficacy (pain, function, frequency of flares, quality of life, uric acid level, radiographic damage) of pegloticase in various doses or as compared to placebo or other interventions for treatment of hyperuricemia in patients with chronic gout. We searched six databases: The Cochrane Central Register of Controlled Trials (CENTRAL), via The Cochrane Library, OVID MEDLINE, CINAHL (via EBSCOHost), OVID SPORTdiscus, EMBASE and the Science Citation Index (Web of Science). All published randomized controlled trials (RCTs) or controlled clinical trials that compared various doses of pegloticase alone or pegloticase alone or in combination with other urate-lowering or anti-inflammatory medications to placebo alone or placebo in combination with these medications, in patients with gout. Two review authors (AA, JS) independently extracted data from the included trials, including trial and population characteristics, primary and secondary outcomes. For dichotomous and continuous outcomes, we calculated the risk ratio and mean difference, respectively with 95% confidence interval. Major outcomes were: (a) frequency of gout flares and change in serum uric acid; and (b) safety: adverse events, serious adverse events, withdrawals and death. Minor/secondary outcomes were pain, patient/physician global assessment, tophus burden, health related quality of life, function and radiographic progression. Only one open-label, phase-II RCT (n=41) met the selection criteria that compared various doses of pegloticase without comparison to placebo or another treatment. Patients were randomized to one of the four doses of pegloticase for 12 to 14 weeks - 4mg every 2 weeks, 8mg every 2 weeks, 8mg every 4 weeks and 12mg every 4 weeks. Percent responders (uric acid below 6 mg/dl 80% or more time) in the four dose groups were 56%, 88%, 52% and 62%. Percent time without hyperuricemia (uric acid below 6 mg/dl) was 78%, 92%, 76% and 76% respectively. No between dose differences were noted. Most common adverse events (10% or more patients) included nephrolithiasis, arthralgia, anemia, dyspnea, headache, muscle spasms, nausea and pyrexia. 89% reported one or more gout flares during the study. Pain, patient/physician global, function, quality of life, tophus size/regression and radiographic progression were not reported in this study. There are no published double-blind, placebo-controlled RCTs of pegloticase. More evidence is needed to assess risks/benefits of pegloticase in patients with chronic gout.

Quality of care indicators for gout management.

Despite the significant health impact of gout, there is no consensus on management standards. To guide physician practice, we sought to develop quality of care indicators for gout management. A systematic literature review of gout therapy was performed using the Medline database. Two abstractors independently reviewed each of the articles for relevance and satisfaction of minimal inclusion criteria. Based on the review of the literature, 11 preliminary quality indicators were developed and then reviewed and refined by an initial feasibility panel of community and academic rheumatologists. A twelfth indicator was added at the request of the first panel. Using a modification of the RAND/University of California at Los Angeles appropriateness method (bridging teleconference and white-board Internet technology were added), a second expert panel rated each of the proposed indicators for validity using a 9-point scale, in which ratings of 1-3, 4-6, and 7-9 were considered "invalid," "indeterminate," and "highly valid," respectively. Indicators were considered valid if the median panel rating was > or =7 and there was no evidence of panel disagreement (defined to occur when 2 of 6 panelists provided a validity rating of 1-3 and 2 panelists provided a validity rating of 7-9). Ten of the 12 draft indicators were rated to be valid by our second expert panel. Validated indicators pertained to 1) the use of urate-lowering medications in chronic gout, 2) the use of antiinflammatory drugs, and 3) counseling on lifestyle modifications. Using a combination of evidence and expert opinion, 10 indicators for quality of gout care were developed. These indicators represent an important initial step in quality improvement initiatives for gout care.

INTERMITTENT CONTROL OF HYPERURICEMIA IN THE TREATMENT OF GOUT: 186

The conventional treatment of those patients with gout in whom urate-lowering medication is considered desirable is to administer such drugs continuously for an indefinite period.It has been shown that dissolution rates of urate crystals in normouricemic or hyperuricemic solutions in vitro are very fast compared with rates of crystal growth in supersaturated solutions. Our previous clinical studies have shown that after discontinuing treatment with allopurinol the serum uric acid level returns rapidly to pre-treatment values, but long periods may pass before the return of gouty arthritis. In the light of these observations it seems logical to assess the effect of intermittent control of hyperuricemia in the treatment of gout.In a preliminary trial, six patients have been taking allopurinol for only two months in a year. The biochemical response has been as anticipated - normouricemia during treatment, with hyperuricemia resumed once the drug is stopped. However, to date the clinical response seems to have been comparable to that normally obtained with continuous therapy. The results are sufficiently encouraging to justify setting up a formal trial comparing continuous with intermittent treatment.