Achieve Target Serum Uric Acid Research Articles

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Impact of pharmacist-led collaborative gout clinic on timely achievement of serum uric acid goals

Background The concept of a pharmacist-led collaborative gout clinic is relatively new in Singapore. Objective This study examined the impact of this pilot shared care model on providing dose titration of urate lowering therapy, gout education and patient support to achieve target serum uric acid (sUA) levels. Method A retrospective pre-post study was undertaken to compare outcomes in patients who were started on either allopurinol or febuxostat in the 24 months prior to (Group A: Pre implementation) or 33 months following launch of the collaborative gout clinic (Group B: Post implementation). The collaborative gout clinic comprises of a clinical pharmacist under the supervision of a rheumatologist. Results Of 98 eligible subjects enrolled in our study, there were 50 patients (all prescribed allopurinol) for Group A and 48 patients for Group B (allopurinol n = 29, febuxostat n = 19). Among patients who achieved target sUA level of 360 μmol/L or less at 1 year of drug initiation with use of allopurinol, the median [interquartile range, IQR] time taken to attain target sUA was shorter in Group B than Group A (111 [82–308] days vs. 293 [265–414] days, p = 0.016). As compared to Group A, Group B had lesser patients experiencing gout flare (41.3% vs. 70.0%, p = 0.018) and more patients achieving target sUA (75.9% vs. 22.0%, p &lt; 0.001). Mean ± [standard deviation, SD] daily allopurinol dose to achieve target sUA levels was 276 mg ± [138 mg]. Conclusion Our results demonstrate the use of a pharmacist-led collaborative gout clinic may help to achieve better clinical outcomes in gout management.

Odds of Achieving Target Serum Uric Acid Levels Among Gout Patients: The Role of Rurality in Outcomes and Treatment Adherence.

The goal of this paper was to analyze patient outcomes related to gout treatment including, serum uric acid (sUA) measures and treatment adherence across patients in metropolitan, micropolitan or rural counties. We conducted a drug-disease cohort study among patients with gout initiating urate lowering therapy. The proportion of patients with sUA < 6 mg/dL at 1 year of follow-up is compared over the cohort groups using a chi-square test and adjusted logistic regression. Adherence to urate lowering therapy was calculated using the proportion of days covered (PDC). A T-test was used to compare the average PDC and an adjusted logistic regression model was used to estimate the odds of a PDC greater than 80%. A total of 9922 patients were included in the study. Most patients were in a metropolitan (77.4%) area, followed by micropolitan (11.8%) and finally, (10.8%) in a rural area. We found no statistically significant difference among the proportion of patients achieving target sUA of <6 mg/dL, 37.17% among metropolitan patients, 38.9% among micropolitan patients, and 37.7% for those in a rural area, P-value = .502. The proportion of patients achieving 80% treatment adherence was 49.92% in the metropolitan, 51.78% in the micropolitan, and 55.05% in the rural areas, P-value = .005. Adjusted regression models showed no statistically significant difference in proportions achieving target sUA levels or 80% adherence. Urban patients treated for gout did not have better gout outcomes compared to rural patients. Future research should consider provider-based interventions to improve outcomes.

Comparative efficacy and safety of uricosuric agents in the treatment of gout or hyperuricemia: a systematic review and network meta-analysis.

The current world witnesses a greatly increased prevalence and incidence of hyperuricemia and gout with unfortunately the comparative efficacy and safety of present available uricosuric agents remaining uncertain. We herein aimed to investigate the most appropriate uricosuric agent for gout or hyperuricemia patients. PubMed, Embase, Cochrane Library databases, and ClinicalTrials.gov from inception to 2 July 2022 were searched to retrieve eligible studies assessing efficacy and safety of uricosuric drugs in hyperuricemia or gout patients. Network meta-analysis was carried out using the Stata 16.0 software. Twelve randomized controlled trials comprising 1851 patients were eventually included. Network meta-analysis showed that dotinurad 4mg once daily, verinurad, dotinurad 2mg once daily, dotinurad 1mg once daily, and benzbromarone were the top 5 effective treatments to achieve target serum uric acid. Furthermore, dotinurad 4mg once daily was more effective at achieving urate-lowering targets (RR of dotinurad 4mg once daily vs. probenecid: 1.68, 95% CI [1.13; 2.50]) and safer (RR of probenecid vs. dotinurad 4mg once daily: 1.77, 95% CI [0.69; 4.56]) than probenecid. This network meta-analysis demonstrated an important absolute benefit of dotinurad 4mg once daily to achieve target serum uric acid and low risk of adverse events for drug treatment of gout or hyperuricemia patients. Additionally, verinurad might be used as an alternative uricosuric therapeutic option to dotinurad. These findings provided further comprehensive insight into the treatment value of current uricosuric agents for gout or hyperuricemia. Key Points 1. This is the first systematic review and network meta-analysis examining the efficacy and safety of currently available uricosuric agents in gout or hyperuricemia patients. 2. Recommended doses of dotinurad 4mg once daily used for the treatment of gout or hyperuricemia patients can significantly decrease serum uric acid levels. 3. The present findings will provide further comprehensive insight into the treatment value of certain uricosuric agents for gout or hyperuricemia.

P150 Benzbromarone treatment in complex gout: experience in University Sussex Hospitals (East)

Abstract Background/Aims Benzbromarone is a potent uricosuric drug and has been shown to be highly effective and well tolerated in the management of gout including in impaired renal function. It can be combined with xanthine oxidase inhibitors. There have, however, been reports of severe hepatotoxicity with rare reports of death. These concerns resulted in benzbromarone losing its licence in the UK. The risk of serious hepatotoxicity in Europe is approximately 1 in 17000. Although this drug is still used around the world, in the UK it is used infrequently and restricted to specialist prescribing. We have performed a retrospective review of our experience of benzbromarone use in UHS (East). Our aims were to assess the outcome of benzbromarone in achieving target serum uric acid (SUA) &amp;lt; 0.36 mmol/L in complex gout patients intolerant of or who have contraindications to usual ULTs. Methods Retrospective observational review. Data collected from electronic and paper notes from 2008-2020 in patients who commenced benzbromarone by Rheumatology. Patient demographics, co-morbidities, previous medications, reported symptoms, adverse events, blood monitoring (liver function, renal function and SUA), documented prophylaxis and drug adherence were extracted. Results 54 patients were included in the analysis; five additional patients were excluded due to incomplete data. Mean patient age: 74 years old. Male n = 36 (67%); Female n = 18 (33%). Mean dose of benzbromarone 126mg and median dose 100mg. Previous medication: allopurinol n = 52 (96%), febuxostat n = 16 (30%), sulfinpyrazone n = 2 (4%) patients. Co-morbidities: hypertension n = 41 (76%); hyperlipidaemia n = 15 (28%); ischaemic heart disease/congestive heart failure n = 40 (74%); diabetes n = 18 (33%); obesity= 7 (13%); osteoarthritis n = 44 (81%); renal stones n = 4 (7%). Documented prophylaxis n = 47 (87%). Mean SUA pre benzbromarone treatment with 0.59 mmol/L; 3 months post treatment SUA 0.36 mmol/L and 1 year post treatment SUA 0.34 mmol/L. Achievement of target SUA at 3 months n = 29 (54%) and 1 year n = 24 (44%). 25/54 (46%) patients reported no gout symptoms within the year. 17/54 (31%) patients stopped treatment due to the following adverse events: n = 4 patients transaminitis within the first year of these only two stopped treatment. N = 7 patients stopped due to drug intolerance (six patients gastrointestinal side effect, one patient had rash). N = 3 patients stopped due to reduced renal function. N = 3 patients stopped due to treatment adherence. N = 2 patients died due to natural death unrelated to benzbromarone. Conclusion Our study shows that benzbromarone is effective and tolerated in our patient cohort and is a reasonable second- or third-line option. We ensured patients have regular follow up and blood monitoring monthly for the first 3 months and 3 monthly thereafter to ensure safety. This drug has been recommended as an option in the 2017 BSR gout guidelines. Disclosure K. Halai: None. K.M. Jordon: Other; unpaid Trustee/Director of the UK Gout Society.

How much does fat mass change affect serum uric acid levels among apparently clinically healthy Korean men?

Objective:The aim of this study was to examine the impact of fat mass alteration on serum uric acid (SUA) levels in apparently clinically healthy men.Methods:We evaluated 27,387 men who consecutively underwent health check ups between 2015 and 2017. We assessed the likelihood of achieving a SUA level of <0.41 mmol/L and compared the SUA levels according to fat mass changes.Results:Compared with those without fat mass change (the reference group), the odds ratios (95% confidence interval) of achieving a SUA level of <0.41 mmol/L for fat mass decreases of ⩾2.5, 1.5–2.5, and 0.5–1.5 kg were 1.63 (1.45–1.82), 1.19 (1.06–1.34), and 1.07 (0.97–1.18), respectively, while those for a fat mass increase of ⩾2.5, 1.5–2.5, and 0.5–1.5 kg were 0.71 (0.64–0.78), 0.87 (0.79–0.97), and 0.95 (0.86–1.04), respectively. The corresponding beta-coefficients of SUA levels (mmol/L) were –0.26 [–0.29–(–0.23)], –0.12 [–0.16–(–0.09)], and –0.09 [–0.12–(–0.06)] for fat mass decreases of ⩾2.5, 1.5–2.5, and 0.5–1.5 kg, respectively. Every 1-kg fat mass reduction was associated with 9% increased odds of achieving the target SUA level. The multivariate SUA level difference per 1-kg fat mass gain was 2.97 µmol/L. Similar levels of association persisted among the prespecified subgroups.Conclusion:We quantitatively demonstrated that fat mass reduction contributes to a clinically relevant decrease in SUA levels and a significant increase in the likelihood of achieving target SUA levels. Our findings may help to provide clear clinical guidance on fat mass alteration to reduce SUA levels in patients with hyperuricemia.

Factors associated with achieving target serum uric acid level and occurrence of gouty arthritis: A retrospective observational study of Japanese health insurance claims data.

PurposeThis study assessed factors associated with achieving target serum uric acid (sUA) level and occurrence of gouty arthritis in Japanese clinical practice.MethodsJapanese health insurance claims and medical check‐up data from October 2015 to March 2017 were analyzed to assess factors associated with target sUA achievement in gout and asymptomatic hyperuricemia and gouty arthritis in gout. Target sUA was further assessed by subgroup analysis of urate‐lowering therapy (ULT) prescriptions and outcomes, stratified by renal function.ResultsPatients achieving target sUA tended toward older, female, higher ULT dose, higher adherence, more comorbidities, and/or antidiabetic drugs prescribed. Renal dysfunction and/or diuretic prescriptions were associated with reduced achievement of target sUA. Severe renal dysfunction was particularly influential (odds ratio [OR] = 0.22 [95% confidence interval (CI): 0.10‐0.48] for <15, 0.15 [0.10‐0.23] for ≥15 to <30, compared with eGFR ≥90 mL/min/1.73 m2). Across all renal function categories, mean prescribed ULT dose was low (febuxostat 17.0‐21.0 mg/day, allopurinol 123.1‐139.6 mg/day), and target sUA achievement was reduced among renal dysfunction patients. Gouty arthritis was more likely in patients with a prior history of such occurrences, and less likely for higher ULT adherence, sUA monitored regularly at medical facilities, and/or more comorbidities.ConclusionIn a real‐world setting, severe renal dysfunction is the most important risk factor for failure to achieve the target sUA, suggesting suboptimal disease management in patients with gout or hyperuricemia complicated by this condition. Findings associated with gouty arthritis suggest that these occurrences could be successfully managed by regular monitoring of sUA and closer adherence to ULT.

Ultra-performance hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma: Application to pharmacokinetic study in rats.

A fixed dose combination of lesinurad and allopurinol has been recently approved by USFDA and EMA for treatment of gout-associated hyperuricemia in patients who have not achieved target serum uric acid levels with allopurinol alone. In this study, an ultra-performance hydrophilic interaction liquid chromatography (UPHILIC) coupled with tandem mass spectrometry method was developed and validated for simultaneous determination of allopurinol, oxypurinol and lesinurad in rat plasma. Liquid liquid extraction using ethyl acetate as extracting agent was used for samples extraction procedure. Acquity UPLC HILIC column (100 mm x 2.1, 1.7μm) was used for separation of allopurinol, oxypurinol, lesinurad and internal standard (5-Florouracil). The mobile phase consisting of acetonitrile, water and formic acid (95:5:0.1, v/v/v), were eluted at 0.3 mL/min flow rate having total chromatographic run time of 3 min per sample. The analytes were detected on Acquity triple quadrupole mass spectrometer equipped with a Z-Spray electrospray ionization (ESI). The ESI source was operated in negative mode and multiple reaction monitoring was used for ion transition for all compounds. The precursor to product ion transition of m/z 134.94 > 64.07 for allopurinol, 150.89 > 41.91 for oxypurinol, 401.90 > 176.79 for lesinurad and 128.85 >41.92 for internal standard were used for identification and quantification. The calibration curves for all analytes were found to be linear with weighing factor of 1/x2 using regression analysis. The developed assay was successfully applied in an oral pharmacokinetic study of allopurinol, oxypurinol and lesinurad in rats.

Achievement of Target Serum Uric Acid Levels and Factors Associated with Therapeutic Failure among Japanese Men Treated for Hyperuricemia/Gout.

Objective To assess the rate of successfully achieving treatment goals among Japanese men with hyperuricemia/gout and identify factors influencing the success rate. Methods This cross-sectional study, conducted from January to December 2012, examined the serum uric acid (SUA) levels and clinical characteristics of 2,103 men with hyperuricemia/gout selected from an initial population of 136,770 individuals who participated in a workplace health checkup. The success rates (defined as SUA ≤6.0 mg/dL) were calculated, and a multivariate analysis was used to identify factors associated with “therapeutic failure” to achieve target SUA levels. Results The rate of successfully achieving the target SUA level was 37.5%. The body mass index (BMI) was significantly associated with therapeutic failure [25.0≤ Category (C)2<27.5, adjusted odds ratio (AOR) =1.35; 27.5≤C3<30.0, AOR=1.69; C4 ≥ 30.0, AOR=1.94; relative to C1<25.0]. A significant positive association was also observed between waist circumference (WC) and therapeutic failure (85≤C2<90, OR=1.29; 90≤C3<95, OR=1.41; 95≤C4, OR=2.28; relative to C1<85.0 cm). Those with higher BMI/WC measurements were significantly more likely to have higher SUA levels than those with lower such measurements. The ongoing intake of dyslipidemia medication was identified as a protective factor against therapeutic failure. Discussion Our findings suggest a possible association between obesity and therapeutic failure, underscoring the importance of maintaining lipid profiles as part of managing SUA levels. Better management of both obesity and dyslipidemia may prevent future cardiovascular disorders by ensuring healthier SUA levels.

Preparation, Pharmaceutical Properties and Stability of Lesinurad Co-crystals and Solvate

Lesinurad is a BCS class 2, low solubility drug, indicated for hyperglycemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. Co-crystallization and solvate formation with pharmaceutically acceptable coformers and solvents are one of the best ways to improve solubility of BCS class 2 drugs. Lesinurad DMSO (dimethyl sulphoxide) solvate (1:1 mole ratio), urea and 4-Hydroxy benzoic acid co-crystals (1:1 mole ratio) prepared and scaled up to 100g and characterized using PXRD, FTIR, DSC, TGA, solid state 13C NMR and H1 NMR. Unique PXRD pattern, red shift in acid carbonyl stretching of Lesinurad in DMSO solvent, Urea co-crystal and parahydroxybenzoic acid co-crystals are the evidence of solvate and co-crystal formation. Urea co-crystal is further characterized using 13C solid state NMR. Deshielding of acid carbonyl carbon from δppm of 168.98 to 173.12 and shielding of urea carbonyl carbon from δppm of 169 to 164.56 indicates co-crystal formation between lesinurad and urea. DMSO solvate has shown 1.26 fold increase in Intrinsic dissolution rate measurement (IDR) over marketed Form-II and urea co-crystal. DMSO solvate, urea and 4-Hydroxy benzoic acid cocrystals of lesinurad are stable for six months at 40 °C and 75%RH.

Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To evaluate the efficacy and safety of lesinurad for the treatment of hyperuricemia in patients with gout. Systematic review and meta-analysis of randomized controlled trials (RCTs). Five RCTs, which included 1959 patients, compared the efficacy and safety of lesinurad in patients with hyperuricemia associated with gout. Relevant studies were identified from PubMed, EMBASE, Cochrane Library databases, and the ClinicalTrials.gov registry. Two reviewers independently assessed the studies. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random-effect model. The primary outcomes were the proportion of patients achieving target serum uric acid (sUA) levels by month 6 and the mean sUA levels at month 6 and month 12. Gout-related outcomes were also assessed. The secondary outcome was the number of treatment-emergent adverse events (TEAEs). Compared with xanthine oxidase inhibitor (XOI) monotherapy, lesinurad 200mg or 400mg in combination with allopurinol or febuxostat exhibited a higher proportion of patients achieving target sUA levels of < 6.0mg/dl or < 5.0mg/dl, respectively, by month 6. Lesinurad-plus-XOI groups also significantly sustained lower mean sUA levels at month 6 and month 12 compared to XOI alone group. In gout-related outcomes, no significant treatment group differences favored lesinurad. The number of TEAEs was comparable between the lesinurad 200mg-plus-XOI group and the XOI-monotherapy group. Although lesinurad 400mg monotherapy demonstrated superior efficacy compared with placebo, significantly more TEAEs occurred. Although the combination of lesinurad 200mg and XOI is effective and well tolerated for treating patients with gout who have not achieved an adequate response to XOI monotherapy, clinical gout-related outcomes were not improved. Therefore, additional studies investigating the long-term clinical implication of lesinurad are warranted.

Lesinurad in hyperuricaemia of gout: a profile of its use in the EU

Up to 90% of gout patients experience low uric acid (UA) excretion rather than high UA production. The selective UA reabsorption inhibitor lesinurad (Zurampic®) is an effective and generally well tolerated option for the adjunctive treatment of hyperuricaemia in patients with gout who have not achieved target serum uric acid (sUA) levels with monotherapy with an adequate dosage of a xanthine oxidase inhibitor, a class of drugs that acts on UA production. In phase 3 trials of lesinurad + allopurinol in adults with gout inadequately responsive to allopurinol, and lesinurad + febuxostat in adults with tophaceous gout, the addition of once-daily oral lesinurad enabled many patients to achieve target sUA levels, and improved clinical parameters (e.g. tophus number/size) in the long term.

New urate-lowing therapies.

To discuss recent studies of lesinurad and arhalofenate. Lesinurad acts by blocking urate reabsorption channels URAT-1 and OAT-4. It has urate-lowering effect when used alone and in combination with xanthine oxidase inhibitors (XOIs). Its uricosuric activity depends on glomerular filtration, and its' efficacy is impaired at eGFR less than 30 ml/min. Lesinurad monotherapy (400 mg/day) associates with serum creatinine elevations. However, this risk is substantially attenuated with coprescription of a XOI and when prescribed at a dose of 200 mg/day. Given its' modest urate-lowering effect, and the risk of serum creatinine elevation when used alone, it is licenced for use in combination with XOI for people unable to achieve target serum uric acid with XOI alone. Lesinurad does not have the drug interactions associated with probenecid, however, it is metabolized by CYP2C9, and should be used with caution if CYP2C9 inhibitors are coprescribed. Arhalofenate also acts by blocking URAT-1; however, it also blocks the NALP-3 inflammasome providing gout-specific anti-inflammatory effect. Arhalofenate has a weaker urate-lowering effect than lesinurad and further phase III evaluation is planned. Lesinurad provides an additional option for people with gout unable to achieve target serum uric acid with XOI alone.

Management of gout by UK rheumatologists: a British Society for Rheumatology national audit.

To assess the concordance of gout management by UK rheumatologists with evidence-based best-practice recommendations. Data were collected on patients newly referred to UK rheumatology out-patient departments over an 8-week period. Baseline data included demographics, method of diagnosis, clinical features, comorbidities, urate-lowering therapy (ULT), prophylaxis and blood tests. Twelve months later, the most recent serum uric acid level was collected. Management was compared with audit standards derived from the 2006 EULAR recommendations, 2007 British Society for Rheumatology/British Health Professionals in Rheumatology guideline and the National Institute for Health and Care Excellence febuxostat technology appraisal. Data were collected for 434 patients from 91 rheumatology departments (mean age 59.8 years, 82% male). Diagnosis was crystal-proven in 13%. Of 106 taking a diuretic, this was reduced/stopped in 29%. ULT was continued/initiated in 76% of those with one or more indication for ULT. One hundred and fifty-eight patients started allopurinol: the starting dose was most commonly 100 mg daily (82%); in those with estimated glomerular filtration rate <60 ml/min the highest starting dose was 100 mg daily. Of 199 who started ULT, prophylaxis was co-prescribed for 94%. Fifty patients started a uricosuric or febuxostat: 84% had taken allopurinol previously. Of 44 commenced on febuxostat, 18% had a history of heart disease. By 12 months, serum uric acid levels ⩽360 and <300 μmol/l were achieved by 45 and 25%, respectively. Gout management by UK rheumatologists concords well with guidelines for most audit standards. However, fewer than half of patients achieved a target serum uric level over 12 months. Rheumatologists should help ensure that ULT is optimized to achieve target serum uric acid levels to benefit patients.

Lesinurad: what the nephrologist should know.

Lesinurad is an oral inhibitor of the monocarboxylic/urate transporter URAT1 encoded by the SLC22A12 gene. Market authorization was granted in February 2016 in Europe and December 2015 in the USA. As a potentially nephrotoxic uricosuric drug acting on the kidney, nephrologists should become familiar with its indications and safety profile. The approved indication is treatment of gout in combination with a xanthine oxidase (XO) inhibitor in adult patients who have not achieved target serum uric acid levels with an XO inhibitor alone. It is not indicated for asymptomatic hyperuricaemia or for patients with estimated creatinine clearance <45 mL/min. The only authorized daily dose is 200 mg and cannot be exceeded because of the nephrotoxicity risk. Nephrotoxicity is thought to be related to uricosuria. At the 200 mg/day dose, serum creatinine more than doubled in 1.8% of lesinurad patients (versus 0% in placebo) and in 11% of these it was not reversible. In addition, it is subject to a risk management plan given the potential association with cardiovascular events. In randomized clinical trials, the association of lesinurad with either allopurinol or febuxostat achieved a greater reduction in serum uric acid (∼1 mg/dL lower) than the XO inhibitors alone, and this allowed the serum uric acid target to be met in a higher proportion of patients, which was the primary endpoint. However, no clinical differences were observed in gout flares or tophi, although these were not the primary endpoints.

Novel medication approved for gout

Novel medication approved for gout

A Pharmacist-Staffed, Virtual Gout Management Clinic for Achieving Target Serum Uric Acid Levels: A Randomized Clinical Trial.

Relatively few patients with gout receive appropriate treatment. To determine whether a pharmacist-staffed gout management program is more effective than usual care in achieving target serum uric acid (sUA) levels in gout patients. A parallel-group, randomized controlled trial of a pharmacist-staffed, telephone-based program for managing hyperuricemia vs usual care. Trial duration was 26 weeks. Primary outcome measure was achieving sUA levels at or below 6 mg/dL at the 26-week visit. Secondary outcome was mean change in sUA levels in the control and intervention groups. Participants were adults with recurrent gout and sUA levels above 6.0 mg/dL. Participants were randomly assigned to management by a clinical pharmacist following protocol or to monitoring of sUA levels but management of their gout by their usual treating physician. Of 102 patients who met eligibility criteria, 77 subjects obtained a baseline sUA measurement and were entered into the trial. Among 37 participants in the intervention group, 13 (35%) had sUA levels at or below 6.0 mg/dL at 26 weeks, compared with 5 (13%) of 40 participants in the control group (risk ratio = 2.8, 95% confidence interval [CI] = 1.1 to 7.1, p = 0.03). The mean change in sUA levels among controls was +0.1 mg/dL compared with -1.5 mg/dL in the intervention group (sUA difference = -1.6, 95% CI = -0.9 to -2.4, p < 0.001). A structured pharmacist-staffed program was more effective than usual care for achieving target sUA levels. These results suggest a structured program could greatly improve gout management.

A Real-World Study of Switching From Allopurinol to Febuxostat in a Health Plan Database.

The objective of this study was to assess the real-world comparative effectiveness of continuing on allopurinol versus switching to febuxostat. In a retrospective claims data study of enrollees in health plans affiliated with Optum, we evaluated patients from February 1, 2009, to May 31, 2012, with a gout diagnosis, a pharmacy claim for allopurinol or febuxostat, and at least 1 serum uric acid (SUA) result available during the follow-up period. Univariate and multivariable-adjusted analyses (controlling for patient demographics and clinical factors) assessed the likelihood of SUA lowering and achievement of target SUA of less than 6.0 mg/dL or less than 5.0 mg/dL in allopurinol continuers versus febuxostat switchers. The final study population included 748 subjects who switched to febuxostat from allopurinol and 4795 continuing users of allopurinol. The most common doses of allopurinol were 300 mg/d or less in 95% of allopurinol continuers and 93% of febuxostat switchers (prior to switching); the most common dose of febuxostat was 40 mg/d, in 77% of febuxostat switchers (after switching). Compared with allopurinol continuers, febuxostat switchers had greater (1) mean preindex SUA, 8.0 mg/dL versus 6.6 mg/dL (P < 0.001); (2) likelihood of postindex SUA of less than 6.0 mg/dL, 62.2% versus 58.7% (P = 0.072); (3) likelihood of postindex SUA of less than 5.0 mg/dL, 38.9% versus 29.6% (P < 0.001); and (4) decrease in SUA, 1.8 (SD, 2.2) mg/dL versus 0.4 (SD, 1.7) mg/dL (P < 0.001). In multivariable-adjusted analyses, compared with allopurinol continuers, febuxostat switchers had significantly higher likelihood of achieving SUA of less than 6.0 mg/dL (40% higher) and SUA of less than 5.0 mg/dL (83% higher). In this "real-world" setting, many patients with gout not surprisingly were not treated with maximum permitted doses of allopurinol. Patients switched to febuxostat were more likely to achieve target SUA levels than those who continued on generally stable doses of allopurinol.

Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response.

The first-line treatment of hyperuricemia, which causes gout, is allopurinol. The allopurinol response is highly variable, with many users failing to achieve target serum uric acid (SUA) levels. No genome-wide association study (GWAS) has examined the genetic factors affecting allopurinol effectiveness. Using 2,027 subjects in Kaiser Permanente's Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort, we conducted a GWAS of allopurinol-related SUA reduction, first in the largest ethnic group, non-Hispanic white (NHW) subjects, and then in a stratified transethnic meta-analysis. ABCG2, encoding the efflux pump BCRP, was associated with SUA reduction in NHW subjects (P = 2 × 10(-8) ), and a missense allele (rs2231142) was associated with a reduced response (P = 3 × 10(-7) ) in the meta-analysis. Isotopic uptake studies in cells demonstrated that BCRP transports allopurinol and genetic variants in ABCG2 affect this transport. Collectively, this first GWAS of allopurinol response demonstrates that ABCG2 is a key determinant of response to the drug.

Current gout treatment and flare in South Korea: Prophylactic duration associated with fewer gout flares.

To evaluate treatment patterns and clinical factors affecting gout flare in South Korea. We retrospectively examined data from 401 patients seen at nine rheumatology multicenter clinics, under urate lowering therapy (ULT) more than 6months after stopping prophylactic medication. Demographic data, clinical and laboratory features were collected at the initiation of ULT, upon stopping prophylaxis, and 6months after. The mean age was 52.2years and mean disease duration was 25.0months. The male-to-female count was 387:14. The most common ULT starting agent was allopurinol 83.8%. Colchicine (62.3%) was the most commonly prescribed prophylactic agent. During ULT, 134 of the 401 patients (33.4%) experienced at least one gouty attack in the period from stopping prophylaxis to 6months later. The duration of prophylaxis was different between those with serum uric acid levels below 6mg/dL and those over 6mg/dL (P=0.001). Of the 179 patients (44.6%) who attained target serum uric acid (SUA) levels (6mg/dL) at the end of prophylaxis, those taking <6months of prophylaxis suffered more frequent flares than those taking it ≥6months (42.9% vs. 26.3%, P=0.041). The time interval to the first attack after stopping prophylaxis was shorter in the <6months group than the ≥6months group (13.5weeks vs. 22.5weeks, P=0.007). Prophylaxis more than 6months from initiation of ULT, and achieving target SUA (<6mg/dL) at the time of stopping prophylaxis is associated with fewer gout flares during ULT.