Target Serum Uric Acid Research Articles

The Impact of Uric Acid-Lowering Therapy on the Progression of Non-dialysis Chronic Kidney Disease: A Prospective Cohort Study.

Background Hyperuricemia treatment can positively influence the progression of chronic kidney disease (CKD). This study aimed to evaluate the impact of uric acid-lowering therapy on the progression of CKD after three months. Materials and methods A prospective cohort study was conducted on 126 patients with non-dialysis CKD in Can Tho Central General Hospital, Vietnam, from December 2018 to December 2019. Adopting a questionnaire survey method to collect information, including demographic characteristics, body mass index (BMI), personal history, previous medical history, diet, and use of drugs with the potential to affect the uric acid levels in the blood. Participants also underwent necessary tests, such as serum uric acid, serum creatinine, and blood lipids. Data were analyzed using SPSS software version 26.0(IBM Corp., Armonk, NY). Results The prevalence of hyperuricemia in patients with non-dialysis CKD was 77.8%, and the average serum uric acid was 494.21 ± 131.57 µmol/L. Patients with a high-purine diet were about 18.85 times as likely to have hyperuricemia as those with a low-purine diet (p < 0.001, OR = 18.85, 95%CI: 4.233-83.938). BMI, stages of CKD, and hypertension were associated with the hyperuricemia rate (p < 0.05). After three months of treatment, 46.2% of patients achieved the serum uric acid target, and the patient group combined allopurinol with changing diet had a higher rate than the patient group changing diet only (p = 0.02). There was a moderate inverse correlation between the difference in serum uric acid and the difference in estimated glomerular filtration rate (eGFR) after treatment (r = -0.5, p = 0.001). Conclusions The effective management of hyperuricemia by combining nonpharmacological (changing diet) and/or pharmacological (allopurinol) therapies may meaningfully improve the glomerular filtration rate in non-dialysis CKD patients with hyperuricemia.

Gout and Nutrition

Gout, the most common arthritis worldwide, is closely linked to cardiovascular disease and metabolic syndrome. The most impor-tant risk factor for developing gout is hyperuricemia. Serum uric acid is the end product of purine metabolism and can be partially influenced by dietary changes. Since a quarter of serum uric acid is excreted via the intestine, there is also a connection with diet here - keyword microbiome. Recently, genetic predispositions and drug therapy for gout have come to the fore. However, since cardiovascular comorbidities exist in high frequency, a dietary adjustment also makes sense to improve the comorbidities. Recently, the focus has shifted away from simply reducing purine intake in favor of introducing a largely plant-based diet. Reducing alcohol consumption makes sense for many reasons but does not lead to a significant reduction in serum uric acid. In addition to drug therapy, however, all possibilities should be exploited to enable a rapid reduction in serum uric acid to the target range; a change in diet can contribute to this. A change in diet can also have a positive effect on the frequency of gout flares. Targeted, structured information for patients promotes their knowledge of the disease and motivation to achieve their serum uric acid (SUA) goal. The right diet may be the personal contribution to quickly reaching the SUA target level and freedom from gout flares.

Adherence and Treat-to-Target Benchmarks in Older Adults With Gout Initiating Urate-Lowering Therapy in Ontario, Canada: A Population-Based Study.

We sought to evaluate urate-lowering therapy (ULT) adherence and treatment-to-target (T2T) serum uric acid (SUA) levels among older adults with gout starting ULT. We performed a population-based retrospective cohort study in Ontario, Canada in patients with gout aged ≥66 years newly dispensed ULT between 2010 and 2019. We defined successful T2T as patients having SUA levels <360 μmol/L (6 mg/dL) within 12 months after ULT dispensation. We also assessed adherence to ULT. Multilevel logistic regression clustered by ULT prescriber evaluated patient, physician, and prescription factors associated with reaching target SUA levels. Among 44,438 patients (mean ± SD age 76.0 ± 7.3 years; 64.4% male), 30,057 (67.6%) patients had ≥1 SUA test completed. Overall, 52.3% patients reached SUA target within 12 months, improving from 45.2% in 2010 to 61.2% in 2019 (P < 0.0001). ULT adherence was 55.3% overall and improved annually. Key factors associated with achieving T2T included febuxostat treatment (odds ratio [OR] 11.40, 95% confidence interval [95% CI] 5.10-25.43) (was only dispensed in 88 patients), ULT adherence (OR 5.17, 95% CI 4.89-5.47), allopurinol starting doses >50 mg (OR 2.53, 95% CI 2.14-2.99), colchicine/oral glucocorticoids co-prescription (OR 1.24, 95% CI 1.14-1.34), and ULT prescription from a rheumatologist. Only 52.3% of patients achieved an optimal SUA level within 1 year of ULT initiation. ULT adherence was suboptimal, although improving over time. ULT adherence and higher allopurinol starting doses had the strongest associations of achieving a target SUA level. This study highlights room for improvement in gout management and potential strategies to address care gaps.

Knowledge, Attitudes, and Practices about Hyperuricemia and Gout in Community Health Workers and Patients with Diabetes.

Hyperuricemia exhibits a high incidence among individuals with diabetes; however, the significance of hyperuricemia and gout is often underestimated. This study aimed to assess the knowledge, attitude, and practice of hyperuricemia and gout among community health workers and patients with diabetes. Two questionnaires were designed to investigate knowledge, attitudes, and practices of hyperuricemia and gout among community health workers and patients with diabetes in Chenghua District, Chengdu, from August 2021 to January 2022. A total of 709 community health workers were included, whose average score was 17.74/30. Approximately half of general practitioners (GPs) demonstrated knowledge regarding the target serum uric acid levels for hyperuricemia and gout. Only 11.2% of GPs were fully aware of the preferred medicine for acute gout. The majority of GPs (86.7%) demonstrated limited awareness regarding the contraindications associated with colchicine, while a significant proportion (65.1%) lacked knowledge about the specific classes of drugs that inhibit uric acid synthesis. Among the 508 patients with diabetes included in this survey, 32.3% demonstrated awareness of hyperuricemia, while 60.8% exhibited knowledge regarding gout. The average score attained by these individuals was recorded at 7.21 out of a total of 26 points. The majority of patients with diabetes (87.8%) held the mistaken belief that hyperuricemia definitely led to the development of gout. Almost 66% agreed that a massage or a hot compress could be used when acute gouty arthritis attacks. The knowledge rate of hyperuricemia and gout among community health workers was moderate, while it was low in patients with diabetes.

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

Multicenter randomized controlled trial of intensive uric acid lowering therapy for CKD patients with hyperuricemia: TARGET-UA

BackgroundWe investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients.MethodsThis was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment.ResultsThree hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups.ConclusionThis study did not reveal the benefit of Intensive ULT to improve albuminuria levels.(UMIN000026741 and jRCTs051180146).

Inhibition of the Progression of Chronic Kidney Disease With Hyperuricemia

The final product of the catabolism of purine compounds in humans is uric acid (UA), which is a weak organic acid, over 98% of which is ionized into monosodium urate. UA is excreted by the kidneys, approximately 80-99% is reabsorbed in the proximal tubules of the kidneys. About 20% of UA is excreted through the intestine, where it is destroyed by microflora to carbon dioxide and water. The reference value of UA in blood plasma is 6.5-7 mg/dl in men and 6–6.5 mg/dl in women. The content of UA in the range of 360-400 μmol/l or 6-6.8 mg / dl increases the risk of crystallization under physiological conditions, and regardless of gender. UA levels greater than 7.0 mg/dl are associated with an increased risk of developing gout or nephrolithiasis. Hyperuricemia may occur due to increased production and / or decreased renal excretion of UA. Hyperuricemia is high in the general population and is associated with the development and progression of chronic kidney disease (CKD). Currently, allopurinol and febuxostat are used to correct hyperuricemia. The use of allopurinol should begin with a low dose (50-100 mg/day) and gradually titrate until the target level of UA in the blood is reached or until it is reached to the maximum. If necessary, the dose of allopurinol is increased by 100 mg every 2–4 weeks until the target serum UA level is reached. According to EULAR's recommendations for the treatment of gout, if the target level of UA cannot be achieved with an adequate dose of allopurinol, it should be replaced with febuxostat or uricosuric or a combination of febucostat with uricosuric. Febuxostat is also indicated for allopurinol intolerance. Febuxostat in doses of 80 and 120 mg/day was more effective than allopurinol at a dose of 300 mg/day. With CKD with mild or moderate renal failure, as well as in the elderly, it is not necessary to adjust the dose of febuxostat. The likelihood of reaching the target level of UA in the blood with reduced kidney function is higher in febuxostat. If the patient does not have serious cardiovascular diseases, the patient can be transferred to febuxostat, starting with a dose of 40 mg/day, and gradually titrated, especially in the case of CKD.

Влияние терапии аллопуринолом на функцию почек у пациентов с подагрой (результаты ретроспективного когортного исследования)

Background: the treatment of hyperuricemia in gout is considered a potential nephroprotective factor. However, data on the effect of allopurinol on renal function in targeted therapy are scarce. Aim: to assess the effect of allopurinol on renal function after achieving the target serum uric acid (UA) level in patients with gout. Patients and Methods: this single-center retrospective cohort study compared changes over time in glomerular filtration rate (GFR) in patients with gout who received allopurinol for at least 12 months with serum UA level &lt;360 μmol/L (n=274, study group) and patients with gout who did not receive urate-lowering medications (n=179, comparison group). Results: the mean follow-up period was 1.9 years, which was similar in both groups. The serum UA level decreased significantly from 521±31.1 to 331±21.3 μmol/L (p&lt;0.001) in the study group, while it increased from 517±55.2 to 558±33.3 μmol/L (p&lt;0.001) in the comparison group. The mean daily dose of allopurinol in the study group was 302.2±24.2 mg. The mean GFR was 80.0±28.5 ml/min/1.73 m2 at baseline and 80.8±21.5 ml/min/1.73 m2 at the end of follow-up in the study group, and 78.2±21.5 ml/min/1.73 m2 at baseline and 76.3±27.5 ml/min/1.73 m2 at the end of follow-up in the comparison group. The study group showed significant differences in ∆GFR (0.8±0.002 ml/min/1.73 m2) and ∆creatinine (-0.9±0.003 μmol/L) compared to the comparison group (∆GFR: -1.7±0.002 ml/min/1.73 m2, p=0.003; ∆creatinine: 1.9±0.001 μmol/L, p=0.001). Conclusion: the results suggest that allopurinol, when administered at a dose sufficient to achieve serum UA levels below the target value (&lt;360 μmol/L), can preserve renal function in patients with gout. KEYWORDS: gout, allopurinol, urate-lowering therapy, uric acid, renal function. FOR CITATION: Eliseev M.S., Zhelyabina O.V. Effect of allopurinol on renal function in patients with gout (retrospective cohort study results). Russian Medical Inquiry. 2024;8(2):60–65 (in Russ.). DOI: 10.32364/2587-6821-2024-8-2-2.

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.

COMPARISON BETWEEN RENOPROTECTIVE EFFECTS OF FEBUXOSTAT AND ALLOPURINOL IN CHRONIC KIDNEY DISEASE PATIENTS WITH HYPERURICEMIA

Objective: The objective of the study was to compare the renoprotective effects of febuxostat versus allopurinol in chronic kidney disease patients with hyperuricemia. Methods: One hundred and ten patients were divided randomly into two equal groups: group F (febuxostat) and group A (allopurinol). Group F patients received tablet febuxostat 40 mg OD for 4 months and group A patients received tablet allopurinol 100 mg TDS for 4 months. Following parameters such as estimated glomerular filtration (eGFR) assessment, serum creatinine, serum uric acid (SUA), total serum protein, urine creatinine, urine protein, blood urea, and number of dialysis were carried out and repeated at the end of 1st–4th month to check for the effect of the test drugs on the status of kidney function. Observations: Febuxostat caused more rise in eGFR than allopurinol. Meanwhile, the number of patients with eGFR ≤15/mL/min/1.73 m2 showed no difference between the groups. No patient showed &gt;10% decrease in the eGFR values. Febuxostat showed more decline in SUA levels than allopurinol, although the number of patients reaching the target SUA levels was the same in both groups. Febuxostat led to a more reduction in serum creatinine levels than allopurinol. Urine creatinine and urine albumin levels decline were associated more with febuxostat. No remarkable difference in comparison of both the groups in terms of total serum protein and serum globulin, although a significant rise was seen with febuxostat in serum albumin levels. Both drugs had a similar sequel in declining blood urea nitrogen levels. No discernible difference in the number of dialysis sessions needed by patients in the previous month was seen in the study groups. Conclusion: The present study concluded that febuxostat appears to be a better alternative to allopurinol for chronic kidney disease patients with hyperuricemia. Febuxostat has a superior renoprotective effect than allopurinol.

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.

Hyperuricemia, gout and comorbidity

Hyperuricemia is most often combined with lipid metabolism disorders, modifiable risk factors for coronary heart disease, stroke, abdominal obesity, type 2 diabetes mellitus, arterial hypertension, urolithiasis, chronic kidney disease. Current data indicate the presence of pro-inflammatory, pro-oxidant and vasoconstrictive effects of uric acid, which may contribute to the development of cardiometabolic disorders. Normal serum uric acid levels are &lt;6 mg / dl (&lt;360 mmol / l) for women and &lt;7 mg / dl (&lt;420 mmol / l) for men. Currently, the role of hyperuricemia as an independent biomarker of the risk of cardiovascular events is emphasized. Both gout and subclinical hyperuricemia are associated with unfavorable cardiovascular outcomes. Patients should be informed about the risk factors of hyperuricemia; the need for lifestyle modification, diet compliance, and correction of drug therapy for comorbid conditions. According to international and domestic recommendations, urate-lowering therapy is indicated for asymptomatic hyperuricemia (&gt;360 mmol / l) and high cardiovascular risk. The data available today allow us to consider the target serum uric acid level &lt;5 mg / dl (&lt;300 mmol / l) for patients with high cardiovascular risk, including at least 2 of the following risk factors: hypertension, diabetes mellitus, dyslipidemia, stroke, heart attack, chronic disease kidneys, and &lt;6 mg / dl for patients who do not have these risk factors. The urate-lowering drug is selected taking into account the concomitant pathology and the presence or absence of liver or kidney dysfunction. Xanthine oxidase inhibitors are still the first-line drugs for the correction of hyperuricemia. The superiority of xanthine oxidase inhibitors is due to the potential inhibition of the production of reactive oxygen species and their antioxidant effect. Treatment of gout is aimed at achieving clinical improvement in acute and chronic arthritis, preventing recurrence of arthritis and damage to internal organs, as well as reducing the risks of negative effects on comorbid pathology. Clinicians are faced with the task of controlling cardiovascular diseases in patients with asymptomatic hyperuricemia and gout. Further studies are needed to investigate the relationship between gout, hyperuricemia and increased risk of cardiovascular diseases, as well as to establish a more complete picture of the prevalence of a wide range of comorbid conditions.

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.

Considerations for Choosing First-Line Urate-Lowering Treatment in Older Patients with Comorbid Conditions.

Gout is the most common inflammatory arthritis in adults. The prevalence of gout increases with age. Urate-lowering treatment (ULT) among older patients is often challenging in that patients frequently suffer insufficient effectiveness or adverse events due to comorbidities, concurrentmedications, and altered pharmacokinetics. The large-scale randomized controlled trials (RCTs) directly investigating gout patients regarding cardiovascular (CV) safety have only recently been introduced; CARES and FAST compared the CV safety of the two xanthine oxidase inhibitors (XOis), febuxostat versus allopurinol, in patients with gout. Based on the CARES trial that showed CV concerns with febuxostat, the current international guidelines recommend allopurinol as first-line ULT in gout, while preserving other agents as a second-line treatment, despite a higher potency of febuxostat. XOis would be more suitable than uricosurics to treat older patients with gout due to the high prevalence of chronic kidney disease (CKD) in older patients. However, allopurinol alone might not achieve the target serum uric acid levels below 6 mg/dL and CKD might confer an increased risk of allopurinol induced cutaneous adverse reactions in older patients. Furthermore, as well as the later analysis of CARES participants who were lost to follow-up, data from the FAST trial and real-world studies suggest non-inferior CV safety for febuxostat compared to allopurinol even in the presence of CV diseases. Thus, febuxostat use in older patients with renal impairment may be more positively considered. The combination therapy of a novel uricosuric, verinurad, plus febuxostat reduced albuminuria in hyperuricemic patients with type 2 diabetes and CKD in a phase 2a trial, and further RCTs are awaited. Finally, the sodium-glucose cotransporter-2 inhibitor class of oral hypoglycemic agents, known to exert beneficial CV and renal effects independent of glycemic control, have shown a uricosuric effect and could be used as adjunctive therapy in older patients with cardiorenal comorbidities.

Achievement of serum uric acid target by rheumatology clinic pharmacists compared with primary care providers in patients with gout

BackgroundThe American College of Rheumatology strongly recommends a treat-to-target management strategy to achieve and maintain serum uric acid (sUA) less than 6 mg/dL to decrease risk of gouty flare recurrence and permanent joint damage. ObjectiveTo compare the effectiveness of rheumatology clinic pharmacists and primary care providers (PCPs) in achieving a target sUA goal in patients with gout. MethodsThis retrospective chart review included patients aged 18 years and older starting urate-lowering therapy (ULT) (allopurinol, febuxostat, or probenecid) for gout between January 1, 2015, and December 31, 2019. Exclusion criteria were ULT use within the previous 6 months, baseline sUA less than 6 mg/dL, and death within 12 months of starting ULT. From ULT initiation, data were collected until sUA less than 6 mg/dL was achieved or a maximum of 12 months. The primary outcome was the percentage of patients who achieved sUA less than 6 mg/dL. Key secondary outcomes were percent reduction in sUA and time to sUA target achievement. ResultsOf 62 patients included in each group, 75.8% of patients in the pharmacist cohort versus 30.6% of patients in the PCP cohort achieved target sUA less than 6 mg/dL (odds ratio 7.09, 95% confidence interval 3.28–16.11, P < 0.001). Patients in the pharmacist-managed group also achieved a greater reduction in mean sUA (−36.7% vs. −26.9% respectively, P = 0.001). Among patients achieving target sUA, median time to target was similar at 92 and 86 days, respectively, despite significantly lower initial mean allopurinol doses in the pharmacist-managed group (102 mg/d vs. 145 mg/d, P < 0.001). ConclusionThe odds of achieving target sUA within 12 months were 7 times higher if gout was managed by a rheumatology clinic pharmacist as compared with a PCP. This study suggests the need for prescriber education and supports expansion of pharmacist-led gout management to primary care settings.

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.

Efficacy of Xanthine Oxidase Inhibitors in Lowering Serum Uric Acid in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Objective: Current guidelines for gout recommend a treat-to-target approach with serum uric acid (SUA). However, there is little evidence for the dose-dependent effects of urate-lowering therapy (ULT). Herein, we analyzed the reported SUA-lowering effect and SUA target achievement differences for various doses of xanthine oxidase inhibitors. Methods: Approved ULT drugs were selected from the FDA Drug Database. We included prospective randomized controlled trials of ULT drugs from ClinicalTrials.gov, articles published in the journal “Drugs”, and Embase, a literature database. A meta-analysis was performed to determine the ability of different ULT drugs and doses to lower and maintain a target SUA < 6 mg/dL. Results: We identified 35 trials including 8172 patients with a baseline SUA of 8.92 mg/dL. The allopurinol, febuxostat, and topiroxostat showed dose-proportional SUA-lowering responses. Compared with allopurinol 300 mg daily, febuxostat 80 mg daily and 120 mg daily more effectively maintained SUA < 6 mg/dL. Conclusion: Allopurinol, febuxostat, and topiroxostat showed dose-proportional ability to lower and achieve a target SUA < 6 mg/dL. Significance and Innovations. We showed dose-dependent SUA lowering effects of allopurinol, febuxostat, and topiroxostat. Febuxostat is effective at ULT compared to allopurinol and could be potentially offered as an alternative agent when patients (1) have CKD, (2) have the human leukocyte antigen HLA-B*5801 allele, and (3) become refractory to allopurinol. Gradual allopurinol dose increase with a lower starting dose is needed in CKD.

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.

Comparative efficacy and safety of topiroxostat at different dosages in hyperuricemic patients with or without gout: A network meta-analysis of randomized controlled trials.

We aimed to assess the relative efficacy and safety of topiroxostat at different dosages in hyperuricemic patients with or without gout. A Bayesian network meta-analysis was performed to combine direct and indirect evidence from randomized controlled trials (RCTs) for evaluating the efficacy and safety of topiroxostat at different dosages, allopurinol 200mg, and placebo in hyperuricemic patients with or without gout. Five RCTs, including 733 patients, fulfilled the inclusion criteria. The number of patients who had achieved a target serum uric acid (sUA) level was significantly higher in the topiroxostat 200mg group than in the placebo group (odds ratio, 1,023; 95% credible interval, 157.7-26,260). Similarly, the number of patients who had achieved the target sUA level was significantly higher with topiroxostat at other dosages and allopurinol than with placebo. The ranking probability based on the surface under the cumulative ranking curve indicated that topiroxostat 200mg was more likely to achieve the best target sUA level, followed by topiroxostat 80mg, allopurinol 200mg, topiroxostat 120mg, topiroxostat 160mg, topiroxostat 60mg, topiroxostat 40mg, and placebo. The frequency of adverse events (AEs) in the placebo group was lower than that in the topiroxostat 40mg, topiroxostat 60mg, and topiroxostat 200mg groups. Topiroxostat 200mg was the most effective treatment option for hyperuricemic patients with or without gout, with an increased risk of AEs.

Comparative efficacy and safety ofdotinurad, febuxostat, and benzbromarone in hyperuricemic patients with or without gout: Anetwork meta-analysis of randomized controlled trials.

We aimed to assess the relative efficacy and safety of dotinurad (2 mg), benzbromarone (50 mg), and febuxostat (40 mg) in hyperuricemic patients with or without gout. A Bayesian network meta-analysis was performed to combine direct and indirect evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of dotinurad (2 mg), benzbromarone (50mg), febuxostat (40 mg), and placebo in hyperuricemic patients with or without gout. Four RCTs, including 516 patients, fulfilled the inclusion criteria. The number of patients who achieved the target serum uric acid (sUA) level was significantly higher in the febuxostat 40-mg group than in the placebo group (OR 660.50, 95% credible interval (CrI) 75.47-19,584.80). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that febuxostat 40 mg was more likely to achieve the best target sUA level (SUCRA = 0.849), followed by dotinurad 2 mg (SUCRA = 0.651), benzbromarone 50 mg (SUCRA = 0.501), and placebo (SUCRA < 0.001). The frequency of adverse drug reactions in the dotinurad 2-mg group, and in the benzbromarone 50-mg group tended to be lower than in the febuxostat 40-mg group. Febuxostat 40 mg and dotinurad 2 mg tended to be more effective than benzbromarone 50 mg, while dotinurad 2 mg and benzbromarone 50 mg tended to be safer than febuxostat 40 mg in hyperuricemic patients with or without gout.