Management Of Hyperuricemia Research Articles

Hyperuricemia: a novel old disorder-relationship and potential mechanisms in heart failure.

Uric acid, the metabolic mediator of gout and urate renal stones, is associated with increased cardiovascular risk burden. Hyperuricemia is an old emerging metabolic disorder, and interaction among uric acid and cardiovascular diseases has been clearly described. Several illness including hypertension, myocardial infarction, metabolic syndrome, and heart failure, are related with uric acid levels increase. In this review, we will discuss the pathophysiology of hyperuricemia and describe the biological plausibility for this metabolite to participate in the pathogenesis of cardiovascular disorders. In particular, we will focus on the implications of hyperuricemia in the onset and progression of heart failure, paying special attention to the pathophysiology and the possible clinical implications. We will conclude by discussing the effects of lowering plasma uric acid concentration on the prognosis of heart failure by reviewing most of available data on the different classes of drugs directly or indirectly involved in the hyperuricemia management.

Prediction of the pharmacokinetics and pharmacodynamics of topiroxostat in humans by integrating the physiologically based pharmacokinetic model with the drug-target residence time model

Topiroxostat is a selective xanthine oxidoreductase (XOR) inhibitor for the management of hyperuricemia in patients with or without gout. In this work, we aim to employ the physiologically based pharmacokinetic (PBPK) model with the drug-target residence time model to predict and characterize both the pharmacokinetics (PK) and pharmacodynamics (PD) of topiroxostat in humans. The plasma concentration-time profile of topiroxostat was simulated based on drug properties and human physiology parameters. The predictive power of this PBPK model was then demonstrated by comparison of stimulated to observed pharmacokinetic parameters. The utility of the model was further demonstrated through predicting the oral absorption and disposition characteristics of topiroxostat in humans. Finally, by combining the PBPK model and the drug-target residence time model, we successfully predicted the target occupancy and built the relationship between PK and PD using in vitro, in vivo and in silico information. The results showed that topiroxostat exhibited significant in vivo pharmacological activity even after the complete clearance of this drug from the liver (target site), which may be due to the long residence time of the binary topiroxostat–XOR complex. This work may be helpful to guide future investigations of topiroxostat and also provides a novel strategy for PK/PD studies.

Rasburicase versus intravenous allopurinol for non-malignancy-associated acute hyperuricemia in paediatric cardiology patients.

Limited data exist for management of hyperuricemia in non-oncologic patients, particularly in paediatric cardiac patients. Hyperuricemia is a risk factor for acute kidney injury and may prompt treatment in critically ill patients. The primary objective was to determine if rasburicase use was associated with greater probability normalisation of serum uric acid compared to allopurinol. Secondary outcomes included percent reduction in uric acid, changes in serum creatinine, and cost of therapy. A single-centre retrospective chart review. A 20-bed quaternary cardiovascular ICU in a university-based paediatric hospital in California. Patients admitted to cardiovascular ICU who received rasburicase or intravenous allopurinol between 2015 and 2016. None. Data from a cohort of 14 patients receiving rasburicase were compared to 7 patients receiving IV allopurinol. Patients who were administered rasburicase for hyperuricemia were more likely to have a post-treatment uric acid level less than 8 mg/dl as compared to IV allopurinol (100 versus 43%; p = 0.0058). Patients who received rasburicase had a greater absolute reduction in post-treatment day 1 uric acid (-9 mg/dl versus -1.9 mg/dl; p = 0.002). There were no differences in post-treatment day 3 or day 7 serum creatinine or time to normalisation of serum creatinine. The cost of therapy normalised to a 20 kg patient was greater in the allopurinol group ($18,720 versus $1928; p = 0.001). In a limited paediatric cardiac cohort, the use of rasburicase was associated with a greater reduction in uric acid levels and associated with a lower cost compared to IV allopurinol.

Second-line treatment with lesinurad and allopurinol versus febuxostat for management of hyperuricemia: a cost-effectiveness analysis for Spanish patients

Introduction/objectivesLesinurad, in combination with allopurinol, has been approved for treatment of patients with gout which do not reach therapeutic serum urate target with xanthine oxidase inhibitors monotherapy. The study aimed to assess the incremental cost-effectiveness ratio of adding lesinurad to allopurinol as second-line therapy, compared to febuxostat for patients with gout in Spain.MethodA Markov model representing disease evolution was used to estimate the lifetime accumulated cost and benefits in terms of quality-adjusted-life-year (QALY). Patients could either continue with second-line treatment with lesinurad (200 mg/daily) plus allopurinol (400 mg/daily) or febuxostat (80 mg/daily) switch to allopurinol monotherapy (271 mg/daily) in case of intolerance or discontinue treatment. The treatment’s efficacy captured in the transition probabilities between health states were derived from CLEAR and EXCEL trials. Quality of life related to gout severity and flare frequency was considered by means of utilities. The total cost estimation (€, 2019) included drug acquisition cost, disease monitoring, and flare management cost. Unitary local costs derived from databases and literature. A 3% annual discount rate was applied for cost and outcomes.ResultsLesinurad plus allopurinol provided higher QALYs (14.79) than febuxostat (14.69). Total accrued cost/patient was lower with lesinurad and allopurinol (€50,631.51) versus febuxostat (€56,698.64). Lesinurad plus allopurinol resulted more effective and less costly (dominant option) versus febuxostat.ConclusionsLesinurad plus allopurinol therapy compared with febuxostat seems an effective option for the management of hyperuricemia in patients who did not reach serum urate target to previous allopurinol monotherapy, associated to cost-savings for the Spanish Health System.Key Points• Lesinurad, in combination with allopurinol, has been recently authorized as second-line treatment of hyperuricemia in gout patients.• Lesinurad plus allopurinol provided higher effectiveness in terms of quality-adjusted-life-years (14.79) than febuxostat (14.69).• Lesinurad plus allopurinol resulted less costly (total cost/per patient) compared with febuxostat.• Lesinurad plus allopurinol resulted a dominant option compared with febuxostat.

Association between three non-insulin-based indexes of insulin resistance and hyperuricemia.

The association between hyperuricemia and insulin resistance (IR) has been demonstrated by many studies, but the traditional IR indexes are too impractical to be used in clinical practice for the recognition of the IR state in individuals with hyperuricemia. Therefore, we aimed to further investigate the association between hyperuricemia and three non-insulin-based IR indexes in this large-scale cross-sectional study. A total of 174,695 adults without self-reported use of antihyperuricemic agents, hypoglycemic agents, or lipid-lowering drugs were included in the current analysis. The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDLc), the product of fasting triglycerides and glucose (TyG), and metabolic score for IR (METS-IR) were calculated. Then, logistic regression analyses were applied to explore their association with hyperuricemia. The TG/HDLc, TyG, and METS-IR all had positive correlations with uric acid level. However, only TG/HDLc and TyG were significantly associated with hyperuricemia in both sexes and body mass index (BMI) classification (the ORs of the highest quartile for each were 6.751 and 1.505 in females and 6.487 and 1.646 in males, respectively). The AUC values of TG/HDLc and TyG to discriminate hyperuricemia were also statistically significant in both sexes and BMI classification (all greater than 0.7). TG/HDLc and TyG are strongly associated with hyperuricemia regardless of BMI classification. These two obtainable and cost-effective non-insulin-based IR indexes could be potential monitors during the management of hyperuricemia and prevention of its IR-driven comorbidities. Key Points • In this large-scale study, we identified TG/HDLc and TyG as indicators for identification of IR in patients with hyperuricemia. • These simple and practical IR indicators are of substantial clinical importance for implementing preventive strategies against IR-driven comorbidities of hyperuricemia.

SERUM URIC ACID AND LONGITUDINAL CHANGES IN LEFT VENTRICULAR STRUCTURE AND FUNCTION IN THE GENERAL POPULATION

Objective: Previous studies showed that serum uric acid as a marker of increased xanthine oxidase activity may be a useful prognosticator for incident heart failure particularly in patients with hypertension. However, population data on the longitudinal changes in left ventricular (LV) structure and function in relation to serum uric acid are sparse. We, therefore, assessed in the general population whether hyperuricemia predicts longitudinal changes in echocardiographic indexes reflecting LV structure and function. Design and method: In 641 randomly recruited Flemish participants (mean age 50.6 years, 50.9% women), we assessed echocardiographic indexes of LV structure and diastolic function at baseline and after 4.7 years. We regressed longitudinal changes in these indexes on baseline uric acid, and reported standardized effect sizes as a percentage of the SD of LV changes associated with a 1-SD of serum uric acid. Results: In multivariable-adjusted cross-sectional analyses, higher serum uric level correlated (P < 0.0018) with greater LV mass index (LVMI) and E/e′ ratio measured at follow-up. From examination 1 to 2, LVMI and E/e′ ratio increased by +3.6 ± 13.2 g/m2 and +0.37 ± 1.46, respectively (P < 0.0001). In longitudinal analyses, after full adjustment, higher baseline serum uric acid independently predicted a greater increase in LVMI (effect size: +14.8%; P = 0.0021) and E/e′ ratio (+21.6%; P < 0.0001) during follow-up. Compared to participants who had normal level of serum uric acid over time (n = 497), subjects with hyperuricemia at both visits (n = 65) experienced worse temporal changes in LVMI (+7.2 g/m2 vs +2.4 g/m2; P = 0.011) and E/e′ ratio (+0.97 vs +0.27; P = 0.0008). Conclusions: Hyperuricemia at baseline predicted worsening of LV diastolic function and LV remodeling over time. These findings suggest the importance of management of hyperuricemia in order to delay or prevent progression of adverse LV remodeling and dysfunction.

The value of low, fixed, single dose rasburicase in the prevention and treatment of tumor lysis syndrome.

e18558 Background: Rasburicase is a recombinant urate oxidase drug approved by the US FDA for the management of hyperuricemia in Tumor Lysis Syndrome (TLS). Recommended dose of 0.2 mg/kg/day for 5 days is expensive and the benefit of extended schedule compared to a single fixed dose of 1.5 mg is not known. Methods: This is a retrospective cohort study done at a tertiary medical center including 165 (144 adult and 21 pediatrics) patients admitted between January 2013 and December 2018. We analyzed the efficacy of single low dose rasburicase 1.5 mg irrespective of bodyweight in adults and in children a dose of 0.15 mg/kg (maximum 1.5 mg) intravenously over 30 min for prevention and treatment of TLS and subsequent doses were given based on clinical and biochemical response. Plasma samples for uric acid were collected at baseline, 6–24 hrs, 48 hrs post-rasburicase, and daily during treatment. The primary outcome was achieving a uric acid level less than 7.0 mg/dl after a single dose of rasburicase in the groups. Secondary outcomes included need for repeat rasburicase doses, and a cost analysis. Results: Children accounted for 12.1% (n = 20) and adults 87.9% (n = 145). The median ages in pediatric and adult groups were 7.9 years and 54 years respectively. Rasburicase was used prophylactically in 35 (21.2%), for laboratory TLS in 105 (63.6%) and for clinical TLS in 25 (15.2%) patients. SDR prevented laboratory/clinical TLS in 89% of the prophylactic group and prevented clinical TLS in 72% of the laboratory TLS group. However, 92%(n=23) of the patients with clinical TLS required more than one dose rasburicase. The average total monthly cost of rasburicase was reduced by 96% ($2850 to $114) after adoption of the above protocol. Conclusions: Single low dose rasburicase is a highly economical and clinically effective way of managing patients with TLS and could serve as an alternative to the 5-day treatment. This dose, therefore, balances cost and efficacy of treatment.

A critical review on the status of clinical practice guideline development in China and an introduction of the Protocol of '2018 Chinese Society of Endocrinology Guideline for Diagnosis and Management of Hyperuricemia and Gout’

In 2013, the Chinese Society of Endocrinology published the 'Management of hyperuricemia and gout: Chinese experts consensus’. In the following five years, a large number of basic researches, clinical studies, and epidemiological results had emerged and need to be popularized in order to improve the understanding and standardizing management of these conditions in general physicians. On the other hand, the methodology of developing clinical guidelines has become more and more scientific, standardized and international. Therefore, based on the 2013 version of the consensus, Chinese Society of Endocrinology decided to develop a guideline for the diagnosis and management of hyperuricemia and gout under standardized methods and procedures of evidence-based clinical practice guidelines. This article will give a review of the status of clinical practice guideline development in China and explain the methods and procedures followed when developing this guideline. We hope this work may provide some useful recommendations for other developers to draft evidence-based clinical practice guidelines. Key words: Guideline; Hyperuricemia; Gout; Critical review

BPI19-016: Evaluation of the Use of a Single Dose Rasburicase in Prophylaxis and Management of Tumor Lysis Syndrome (TLS) Among Cancer Patients in Qatar

Introduction: Rasburicase is a urate oxidase enzyme used for prophylaxis and treatment of hyperuricemia associated with TLS. The recommended dose of rasburicase is 0.2 mg/kg/day for 5 days; however, recent studies have demonstrated the effectiveness of a single rasburicase dose in prophylaxis and management of hyperuricemia associated with TLS. Our institution’s TLS guideline was updated to recommend the use of a single rasburicase dose (0.2 mg/kg). The primary objective of this study was to assess the efficacy of a single rasburicase dose in controlling uric acid (UA); the secondary objective was to evaluate the impact of the institutional TLS guidelines update on consumption and cost of rasburicase. Methods: This is a single center retrospective cohort study including all patients who received rasburicase from August 2012 to March 2016 at the National Center for Cancer Care and Research (NCCCR) in Qatar. Patients were divided into 2 groups based on the prescribed number of rasburicase doses (single dose vs multiple doses). Collected data included patients’ diagnosis, laboratory parameters rasburicase dose, duration, and number of dispensed vials. UA levels within 24 hours and on day 5 of initial rasburicase dose were evaluated. Risk stratification was determined according to institutional guidelines based on disease, white blood cell count, lactate dehydrogenase level, renal function, and UA level. Results: A total of 103 patients who received rasburicase were evaluated retrospectively; rasburicase was prescribed as single dose for 65 patients (63%) and multiple doses for 38 patients (37%). The majority of patients who received rasburicase as single or multiple doses were at high risk of developing TLS, representing 68% and 84%, respectively. Baseline mean UA levels were similar in both groups: 5.4±2.9 mg/dL vs 4.7±3.2 mg/L respectively (P=.7). Normal or undetectable UA levels were observed within 24 hours in 98% of patients in the single dose group and 100% of patients in the multiple doses group. All patients in both groups had normal UA on day 5 of rasburicase with relatively similar UA levels: 1.5±1.2 mg/dL vs 0.8±1 mg/dL (P=.18). Rasburicase consumption and cost were reduced by 42.5% after the guidelines update. Conclusion: The single rasburicase dose demonstrated efficacy in controlling serum UA levels. Updating the institutional TLS guidelines had a significant impact on rasburicase consumption and led to significant cost reduction.

Febuxostat and Cardiovascular Events: A Systematic Review and Meta-Analysis.

Background Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial. Objective To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group. Methods We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI). Results Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03). Conclusions Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.

A Review on Gouty Arthritis

Gout is the inflammatory disease which is characterised by the deposition of the Mono Sodium Urate in joints. The joint infection is quickly reassured by Non-Steroidal Anti-inflammatory Drugs. The most common symptoms are pain, redness, and swelling. Gout is primarily detected by recognition of the signs and symptoms of Mono Sodium Urate crystals clumps together in the joints especially in phalanges. The major risk factor occurs in young people because of heavy alcohol intake and they may cause the major symptoms. Metabolism of purine in the liver can produce acute as well as chronic conditions of gout. Hence it is considered by repeated; throbbing attacks of severe arthritis the treatment for gouty arthritis are classified into by their types chronic and acute. The prevalence of gout is over comes around 1000 persons. When compared to woman, the action of gout is high in men. Chronicity might be an aspect of inflammatory disease. It produce unrelieved swelling that follows continual attacks of inflammatory disease. Acute gouty arthritis can be managed by using NSAID's and physical exercise and chronic gout can be managed by physician advisable drugs. Pharmacological management of hyper-uricemia in arthritis is mostly terribly successful. Main cause for the treatment malfunction is due to the reduced actions, and patient education improves observance.

&lt;b&gt;Development of Guideline for the management of hyperuricemia and gout in Japan 3rd edition&lt;/b&gt;

&lt;b&gt;Development of Guideline for the management of hyperuricemia and gout in Japan 3rd edition&lt;/b&gt;

Knowledge and practice in the management of asymptomatic hyperuricemia among primary health care physicians in Jeddah, Western Region of Saudi Arabia.

Objectives:To assess knowledge and practice levels in asymptomatic hyperuricemia (AH) and investigate predictors of urate-lowering therapy (ULT) misprescribing among primary health care (PHC) physicians.Methods:A cross-sectional study was conducted among 201 PHC physicians from December 2017 to May 2018. A based clinical guidelines for hyperuricemia management from American Professional Organizations, a semi-structured questionnaire was administered to collect demographic and professional data; knowledge and practice levels in management of AH; and barriers to the management of hyperuricemia and gout, with focus of the misprescribing of ULT in AH. A 2-stage stratified sampling technique was used to select 4 PHC centers were from each of the 5 advisory sectors in Jeddah, Kingdom of Saudi Arabia; and to recruit a minimum of 10 eligible participants per primary health care center (PHCC). Binary logistic regression was used to analyze predictors of ULT misuse in AH.Results:Only 32.8% participating physicians had adequate knowledge about AH. Regarding practice, while majority (88.1%) correctly recommended a low-purine diet and lifestyle changes to patients, almost half misprescribed ULT and 10.9% misprescribed non-steroid anti-inflammatory drugs. Lack of knowledge and awareness about guidelines were the most frequently self-reported barriers to adequate practice. Predictors of ULT misuse included the percentage of patients having gout (1-10%: OR=5.40, p=0.047) or receiving ULT (>10-20%: OR=20.02, p=0.001)among patients seen in clinic, attendance of rheumatology conferences (OR=2.55, p=0.017), and having a close relative with hyperuricemia or gout (OR=2.45, p=0.026).Conclusion:There are inadequate levels of knowledge regarding AH among Saudi PHC physicians increasing risk of malpractice including misprescription of ULT and anti-inflammatory medications.

Association between hyperuricemia and nontraditional adiposity indices.

The association between several novel adiposity indices and hyperuricemia is inconclusive. Therefore, we aimed to investigate this association so as to provide theoretical support for the management of hyperuricemia in overweight/obese individuals. A cross-sectional study was carried out among 174,698 adults. The values of body adiposity index (BAI), conicity index (CI), a body shape index (ABSI), body roundness index (BRI), visceral adiposity index (VAI), lipid accumulation product (LAP) index, and cardiometabolic index (CMI) were divided into four quartiles, and multivariate logistic analysis was used to analyze the association between them and hyperuricemia. Receiver operating characteristic curve and area under curve (AUC) were used to evaluate the power of predictions for hyperuricemia. After adjusting for confounding variables, LAP and CMI exhibited stronger association with hyperuricemia than other indices. The odd ratio (OR) for hyperuricemia in the highest quartile of the LAP and CMI was 2.049 (CI 95% = 1.824-2.302) and 4.332(CI 95% = 3.938-4.765). The AUC value of LAP was 0.632 (95% CI = 0.626-0.637), p < 0.001; and the AUC value of CMI was 0.687 (95% CI = 0.682-0.692), p < 0.001. The optimal cutoff values of LAP and CMI were 26.21 and 0.485, respectively. LAP and CMI, combination of WC and lipid parameters and reliable visceral adiposity indices, were strongly associated with hyperuricemia than other indices. So they could be potential monitoring indicators for hyperuricemia management in overweight/obese individuals.

Febuxostat for the treatment of hyperuricaemia in gout

ABSTRACTIntroduction: Febuxostat is a potent non-purine selective xanthine oxidase inhibitor approved by the FDA in 2009 for management of hyperuricemia in people with gout.Areas covered: The authors summarize the pre-clinical studies and pivotal randomized controlled trials of febuxostat when used as a treatment for hyperuricaemia in goutExpert opinion: Febuxostat has clinical efficacy in serum urate lowering, and long-term use leads to improved outcomes such as gout flare frequency and tophus burden. Recently published post-approval placebo-controlled trials have demonstrated urate-lowering efficacy and safety of febuxostat in patients with chronic kidney disease, and reduced frequency of gout flares in people with early onset of gout. In November 2017, the FDA issued a drug safety communication based on the preliminary results of the CARES trial. This cardiovascular safety study of 6190 patients with gout and established cardiovascular disease comparing febuxostat and allopurinol showed no difference in the primary endpoint (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization), but did report higher all-cause mortality (hazard ratio 1.22) and cardiovascular mortality (hazard ratio 1.34) with febuxostat. Based on currently available data, it seems likely that allopurinol, rather than febuxostat, will remain first line urate-lowering therapy for people with gout.

Management of hyperuricemia and gouty arthritis with unani murakkab advia and Hijama-bil-Shart

Management of hyperuricemia and gouty arthritis with unani murakkab advia and Hijama-bil-Shart

Efficacy and safety of febuxostat for treating hyperuricemia in patients with chronic kidney disease and in renal transplant recipients: A systematic review and meta‑analysis

Febuxostat is potent and well-tolerated in the management of chronic gout. However, its clinical efficacy and safety in the treatment of hyperuricemia in patients with chronic kidney disease (CKD) and in renal transplant recipients have remained to be fully determined. The MEDLINE, EMBASE and Cochrane Library databases were searched for relevant articles. Data were extracted and pooled results were estimated from the standard mean difference (SMD) with 95% confidence intervals (95% CIs). The quality of the studies included was assessed, and their publication bias was examined. Four prospective randomized controlled trials and two retrospective observational studies were included in the systematic review and meta-analysis. Febuxostat administration significantly reduced the serum uric acid concentration in patients with CKD and in renal transplant recipients when compared with allopurinol or placebo in the short-term (1 month: SMD, −2.24; 95% CI, −3.59 to −0.89; P-value of SMD=0.001; I2, 92.4%; 3 months: SMD, −1.20; 95% CI, −2.04 to −0.36; P-value of SMD=0.005; I2, 88.9%; 6 months: SMD, −1.49; 95% CI, −2.68 to −0.30; P-value of SMD=0.014; I2, 92.9%). Furthermore, the increase in the estimated glomerular filtration rate in the febuxostat group was significantly higher than that in the control group (SMD, 0.30; 95% CI, 0.031 to 0.58; P-value of SMD=0.029; I2, 0.0%). No significant difference in the changes in serum creatinine (Scr), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) was identified between the two groups (Scr: SMD, −0.17; 95% CI, −0.97 to 0.63; P-value of SMD=0.67; I2, 79.2%; LDL: SMD, −0.21; 95% CI, −0.49 to 0.07; P-value of SMD=0.13; I2, 34.1%; HDL: SMD, −0.05; 95% CI, −0.70 to 0.61; P-value of SMD=0.89; I2, 69.2%). In conclusion, febuxostat is a potent and well-tolerated agent for the short-term management of hyperuricemia in patients with CKD and in renal transplant recipients. However, these data should be interpreted with caution due to the varied design of the studies included in the present meta-analysis.

Efficacy and safety of febuxostat extended release and immediate release in patients with gout and moderate renal impairment: phase II placebo-controlled study

BackgroundFebuxostat immediate release (IR), a xanthine oxidase inhibitor, is indicated for the management of hyperuricemia in patients with gout by lowering urate levels. An extended release (XR) formulation of febuxostat was developed to provide equal or superior efficacy on urate lowering compared with the IR formulation and potentially lower the risk of treatment-initiated gout flares due to an altered pattern of drug exposure. The present study evaluated the efficacy and safety of febuxostat XR and IR formulations in patients with gout and moderate renal impairment (estimated glomerular filtrate rate ≥ 30 and < 60 ml/min).MethodsThis was an exploratory, 3-month, phase II, multicenter, placebo-controlled, double-blind proof-of-concept study. Patients (n = 189) were randomized 1:1:1:1:1 to receive placebo or febuxostat IR 40 mg, XR 40 mg, IR 80 mg, or XR 80 mg once daily. Endpoints included: proportion of patients with serum uric acid (sUA) < 5.0 mg/dl at month 3 (primary endpoint), proportion of patients with sUA < 6.0 mg/dl at month 3, and proportion of patients with ≥ 1 gout flare requiring treatment over 3 months.ResultsAt month 3, all febuxostat treatment groups were associated with greater proportions of patients achieving sUA < 5.0 mg/dl (p < 0.05 vs placebo). A greater proportion of patients receiving XR 40 mg achieved sUA < 5.0 mg/dl versus those receiving IR 40 mg (p = 0.034); proportions were similar in the IR 80 mg and XR 80 mg groups. Higher proportions of febuxostat-treated patients achieved sUA < 6.0 mg/dl at month 3 (p < 0.05 vs placebo) and experienced ≥ 1 gout flare (significant for all comparisons, except XR 40 mg). Incidences of treatment-related adverse events were low across all treatment groups; the majority were mild or moderate with no apparent trends correlating with IR or XR doses. The most common treatment-emergent adverse event was hypertension. One death (unrelated to the study drug) was reported.ConclusionsThese exploratory data demonstrate that febuxostat (XR and IR) formulations were effective and well tolerated in patients with gout and moderate renal impairment.Trial registrationClinicalTrials.gov, NCT02128490 Registered on 29 April 2014.

Glycogen storage disease type Ⅰa: a rare cause of gout in adolescent and young adult patients

Objective: To analyze the clinical features of secondary gout in glycogen storage disease type Ⅰa (GSD Ⅰa), so as to improve the awareness of this disease. Methods: The clinical features, laboratory findings, treatments and prognosis of 5 GSD Ⅰa patients with secondary gout who had been admitted to the Peking Union Medical College Hospital during 2006 to 2016 were collected and analyzed. GSD Ⅰa was confirmed by liver biopsy and genotyping. Results: Among the 5 patients (median age: 27 years), 3 were males and 2 were females. The mean age of gout onset was 17 ranging from 10 to 22 years old. The common manifestations of GSD included hepatomegaly since childhood, hypoglycemia, growth retardation, anemia, hyperlactacidemia and hyperlipidemia. All the 5 patients were complicated with gouty tophi and kidney stone. Gouty tophi and kidney stone were identified 3.8 years and 10.2 years after the first occurrence of articular symptoms, respectively. Renal damage occurred in 3 cases. All the patients underwent several therapeutic modalities including lifestyle intervention, allopurinol, and raw corn starch treatment. Conclusions: Determination of the presence of primary disease should be performed actively for young-onset gout with early occurrence of gouty tophi. GSD should be suspected if there exist clinical manifestations like hepatomegaly, recurrent hypoglycemia, growth retardation. Early management of hyperuricemia and gout in GSD patients is important to prevent complications and improve prognosis.

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.