Analysis of the effectiveness and safety of Jiedu Xiezhuo Yishen Tang in the treatment of gouty arthritis: An observational study.

This study is for exploring the effectiveness and security of Jiedu Xiezhuo Yishen Tang in the treatment of gouty arthritis. This retrospective study collected 100 patients with gouty arthritis between February 2022 and February 2023. According to the different treatment methods, the data of patients were divided into control group and experimental group. The control group received routine treatment with benzbromarone, while the experimental group received additional treatment with Xuedu Xiezhuo Yishen Tang on the basis of the control group. The evaluation indicators for the effectiveness of treatment include serum levels of 8-hydroxydeoxyguanosine, 3-NT, interleukin-6, interleukin-10, interleukin-1ß, tumor necrosis factor-α, C-reactive protein, erythrocyte sedimentation rate, urea nitrogen, creatinine, evaluation of knee joint function and pain level, traditional Chinese medicine syndrome score, and safety evaluation. After treatment, the overall treatment effect of the experimental group reached 98%, while the control group was 78%. After treatment, the differences in various indicators possessed statistical significance (SS) (P < .05). In the Lysholm score, the improvement in the experimental group was markedly more excellent than the control group, and the difference possessed SS (P < .05). In the NRS score, the experimental group's NRS score decreased from 8.39 to 1.08 before and after treatment, while the control group only decreased to 3.61. In addition, both groups of patients showed significant improvement in the joint score in the Traditional Chinese medicine syndrome sub-items. The experimental group was able to effectively improve symptoms such as joint pain, joint redness and swelling, joint fever, and limited joint mobility. After treatment, the incidence of adverse reactions in the experimental group was only 8%, while the incidence of adverse reactions in the control group was 24%. After statistical analysis of the incidence of adverse reactions during treatment among the participants, it was found that the difference possessed SS (P < .001). The combination treatment of Jiedu Xiezhuo Yishen Tang and benbromarone can effectively improve oxidative stress response and significantly reduce blood uric acid levels. Meanwhile, this combination therapy can effectively inhibit inflammatory reactions, significantly alleviate knee joint pain, and promote the recovery of knee joint function. This treatment regimen has lower toxic side effects and higher safety.

Benzbromarone as adjuvant therapy for cystic fibrosis lung disease: a pilot clinical trial.

OBJECTIVE: Cystic fibrosis (CF) affects multiple organs, the most severe consequences being observed in the lungs. Despite significant progress in developing CF transmembrane conductance regulator-specific treatments for CF lung disease, exploring alternative CF-targeted medications seems reasonable. We sought to evaluate the potential beneficial effects of oral benzbromarone as an adjuvant therapy in CF patients with reduced lung function. METHODS: This was a prospective open-label pilot study of oral benzbromarone (100 mg/day) administered once daily for 90 days. Patients were followed at a tertiary referral center in southern Brazil. Safety was assessed by the number of reported adverse events. Secondary objectives included percent predicted FEV1 (FEV1%) and pulmonary exacerbations. RESULTS: Ten patients were enrolled. Benzbromarone was found to be safe, with no serious drug-related adverse events. Eight patients completed the study; the median relative change in FEV1% tended to increase during the treatment, showing an 8% increase from baseline at the final visit. However, a nonparametric test showed that the change was not significant (p = 0.06). Of a total of ten patients, only one experienced at least one pulmonary exacerbation during the study. CONCLUSIONS: Oral benzbromarone appears to be safe, and improved FEV1% has been observed in patients with CF. Further assessment in larger trials is warranted to elucidate whether oral benzbromarone can be a potential adjuvant therapy for CF.

Urate-lowering agents do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout: a prospective open-label cohort study.

OBJECTIVE: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting. METHODS: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18-45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3. RESULTS: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9-54.3] vs 48.4%, [27.4-67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6-69.92] vs 58.5 M/mL, [49.8-116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well. CONCLUSION: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout.

Comparison of the efficacy and safety of benzbromarone and febuxostat in gout and hyperuricemia: a systematic review and meta-analysis.

OBJECTIVE: Urate-lowering therapy (ULT) is widely recognized as the primary treatment for hyperuricemia and gout. Xanthine oxidase inhibitors (XOI), particularly febuxostat, have gained popularity as a frontline approach. However, the divergent efficacy and safety between febuxostat and the traditional ULT drug, benzbromarone, remain poorly understood. This knowledge gap necessitates a comprehensive analysis and evidence update to guide drug selection for physicians and patients. METHOD: We conducted a systematic analysis by extracting relevant clinical studies from four medical literature databases. Forest plots, funnel plots, sensitivity analysis, Egger's test, and subgroup analysis were utilized to compare relevant indicators. RESULTS: The advantages and disadvantages of the two drugs were evaluated based on various indicators such as serum uric acid (SUA), triglyceride (TG), urinary uric acid (UUA), white blood cell count (WBC), total cholesterol (TC), blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine (SC). Benzbromarone demonstrated better efficacy in rapidly reducing SUA levels and inhibiting inflammation for hyperuricemia and gout patients. Febuxostat was slightly less effective in lowering SUA, but there was no significant difference in its impact on liver and kidney function after long-term use. CONCLUSION: This study highlights the superiority of benzbromarone in rapidly reducing SUA and inhibiting inflammation. Febuxostat shows comparable effects on liver and kidney function after long-term use. These findings provide valuable insights for clinicians and patients in drug selection. Key Points • Benzbromarone stands out as a highly effective treatment for hyperuricemia and gout, offering rapid reduction of serum uric acid levels and potent anti-inflammatory effects. • When it comes to long-term use, febuxostat demonstrates comparable effects on liver and kidney function. This provides reassurance for patients who require extended treatment duration. • Moreover, our study goes beyond previous research by presenting a more comprehensive and detailed analysis.

Inhibition of mucus secretion by niclosamide and benzbromarone in airways and intestine.

The Ca2+ activated Cl- channel TMEM16A (anoctamin 1; ANO1) is expressed in secretory epithelial cells of airways and intestine. Previous studies provided evidence for a role of ANO1 in mucus secretion. In the present study we investigated the effects of the two ANO1-inhibitors niclosamide (Niclo) and benzbromarone (Benz) in vitro and in vivo in mouse models for cystic fibrosis (CF) and asthma. In human CF airway epithelial cells (CFBE), Ca2+ increase and activation of ANO1 by adenosine triphosphate (ATP) or ionomycin was strongly inhibited by 200 nM Niclo and 1 µM Benz. In asthmatic mice airway mucus secretion was inhibited by intratracheal instillation of Niclo or Benz. In homozygous F508del-cftr mice, intestinal mucus secretion and infiltration by CD45-positive cells was inhibited by intraperitoneal injection of Niclo (13 mg/kg/day for 7 days). In homozygous F508del-cftr rats intestinal mucus secretion was inhibited by oral application of Benz (5 mg/kg/day for 60 days). Taken together, well tolerated therapeutic concentrations of niclosamide and benzbromarone corresponding to plasma levels of treated patients, inhibit ANO1 and intracellular Ca2+ signals and may therefore be useful in inhibiting mucus hypersecretion and mucus obstruction in airways and intestine of patients suffering from asthma and CF, respectively.

Uric acid-lowering therapy with benzbromarone in hypertension with asymptomatic hyperuricemia: a randomized study focusing left ventricular diastolic function.

BACKGROUND: Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure with preserved ejection fraction (HFpEF). However, there is limited evidence on the effect of uric acid-lowering therapy on left ventricular (LV) diastolic function in this population. In this randomized study, we prescribed benzbromarone, a uric acid-lowering drug, to those with hypertension and asymptomatic hyperuricemia to investigate its clinical benefits by evaluating LV diastolic function, incidence of HFpEF and hospitalization for heart failure and cardiovascular death. METHODS: 230 participants were randomly assigned into two groups: uric acid-lowering group (benzbromarone) and control groups (without uric acid-lowering drug). The primary endpoint was LV diastolic function evaluated by echocardiography. The secondary endpoint of composite endpoints is the combination of new-onset HFpEF, hospitalization for heart failure and cardiovascular death. RESULTS: After a median of 23.5 months' follow-up (16-30 months), the primary endpoint reflected by E/e' in benzbromarone group reached a significant improvement when compared to control group (p <.001). Composite endpoints occurred in 11 patients of the control group while only 3 patients occurred in the benzbromarone group (p = .027). We also presented the favorable trend of freedom from the composite endpoints or new-onset HFpEF using Kaplan-Meier curve by log-rank test in benzbromarone group (p = .037 and p = .054). CONCLUSIONS: Our study demonstrated the efficiency of benzbromarone in hypertensive patients with concomitant asymptomatic hyperuricemia, including the benefits on ameliorating LV diastolic dysfunction as well as improving composite endpoints.

Comparison of benzbromarone and allopurinol on the risk of chronic kidney disease in people with asymptomatic hyperuricemia.

OBJECTIVE: The objective of the study was to compare the relative effects of benzbromarone and allopurinol on the risk of developing chronic kidney disease in persons with asymptomatic hyperuricemia. METHODS: A retrospective cohort study was conducted to analyze a 2003-2015 national database including all claims data of 2 million beneficiaries in Taiwan. Asymptomatic hyperuricemia was defined as follows: persons using urate-lowering drugs who never developed gout flares. The benzbromarone group included persons ages 20-84 that had asymptomatic hyperuricemia and received benzbromarone alone. The allopurinol group included persons ages 20-84 that had asymptomatic hyperuricemia and received allopurinol alone. The maximum follow-up time was set as 5 years in this study. The main outcome was defined as follows: persons were newly diagnosed with chronic kidney disease. A Cox proportional hazards regression analysis was performed to test the association between variables and the risk of chronic kidney disease. RESULTS: After propensity score matching, 9107 persons in the benzbromarone group and 4554 persons in the allopurinol group were eligible for the study. Approximately 71% of the study subjects were males. The mean age was 56 years old. The incidence rate of chronic kidney disease was lower in the benzbromarone group than in the allopurinol group (1.18 versus 1.99/per 100 person-years, incidence ratio = 0.60, and 95% confidence interval = 0.52-0.68).The Cox proportional hazards regression analysis disclosed that after adjusting for co-variables, there was a decreased risk of developing chronic kidney disease in the benzbromarone group as compared with the allopurinol group (hazard ratio = 0.59, 95% confidence interval = 0.52-0.67 and P<0.001). CONCLUSIONS: The use of benzbromarone is associated with a lower hazard of developing chronic kidney disease as compared to allopurinol use among persons ages 20-84 with asymptomatic hyperuricemia. More studies are needed to confirm our findings.

Comparison of the efficacy of febuxostat vs. benzbromarone in the treatment of gout: a meta-analysis in Chinese gout patients.

OBJECTIVE: Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to compare the efficacy of febuxostat and benzbromarone in the treatment of gout. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for articles related to febuxostat and benzbromarone in the treatment of gout from inception to January 7, 2023. Titles and abstracts were reviewed in accordance with predesigned inclusion and exclusion criteria, and data were extracted independently. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies, and the continuous variables were expressed as the standard mean square error (SMD) by STATA 16 (Stata Corp., College Station, TX, USA). The sensitivity analysis was conducted by randomly removing a study, and the heterogeneity was analyzed by funnel plots and Egger's test. RESULTS: According to the search strategy, a total of 1,043 publications were retrieved from the three aforementioned databases, of which 45 publications were excluded due to duplication. Fourteen studies remained after screening titles and abstracts, and a total of 7 studies met the inclusion criteria after a comprehensive evaluation of the 14 studies. Meta-analysis showed that the uric acid (UA)-reducing effect of febuxostat is better than that of benzbromarone, while febuxostat showed a better ability to improve the estimated glomerular filtration rate (eGFR) and reduce Cr and blood urea nitrogen (BUN). In terms of hepatotoxicity, benzbromarone was not as potent as febuxostat in increasing alanine transaminase (ALT) and aspartate transaminase (AST), suggesting that benzbromarone has less hepatotoxicity. Moreover, there was no significant difference in the effect on blood lipid levels between the two drugs. CONCLUSIONS: The beneficial effect of febuxostat on renal function-related indexes such as the eGFR, Cr and BUN is significant, while benzbromarone is more effective in reducing UA and has relatively less hepatotoxicity. The specific efficacy of the two drugs needs to be confirmed by further research.

Discovery of novel benzbromarone analogs with improved pharmacokinetics and benign toxicity profiles as antihyperuricemic agents.

Benzbromarone (BM) is a potent URAT1 inhibitor approved for the treatment of gout. However, the low URAT1-selectivity and hepatotoxcity limit its clinical use. To solve these problems, we rationally designed and synthesized a series of BM derivatives by chemotype hybridization and bioisosteric replacement. Most compounds exhibited potent inhibitory activities against URAT1 with IC50 values ranging from 5.83 µM to 0.80 µM. Among them, JNS4 exhibited the highest URAT1 inhibitory activity with an IC50 of 0.80 µM, comparable to that of BM (IC50 = 0.53 µM). Molecular dynamic simulations showed that JNS4 formed π-cation interaction with R477, the same as BM. Different from BM, JNS4 bound to W357 and H245 via π-π interactions and formed a hydrogen bond with S35, which might contribute to the high URAT1 binding affinity of JNS4. JNS4 hardly inhibited GLUT9 (IC50 > 20 µM), another urate reabsorption transporter. In addition, JNS4 showed little inhibitory effects against OAT1 and ABCG2 with IC50 of 4.04 µM and 10.16 µM, respectively. Importantly, JNS4 displayed higher in vivo urate-lowering effects at doses of 1-4 mg/kg in a mouse model of hyperuricemia, as compared to BM and lesinurad. Furthermore, JNS4 possessed favorable pharmacokinetic properties with an oral bioavailability of 55.28%, significantly higher than that of BM (36.11%). Moreover, JNS4 demonstrated benign toxicity profiles (no cytotoxicities against HepG2 and HK2 cells; no hepatic and renal toxicities observed in vivo). Collectively, these results suggest that JNS4 represents a novel, safe and selective URAT1 inhibitor with excellent druggabilities and is worthy of further investigation as an anti-hyperuricemic agent.

Superiority of Low-Dose Benzbromarone to Low-Dose Febuxostat in a Prospective, Randomized Comparative Effectiveness Trial in Gout Patients With Renal Uric Acid Underexcretion.

OBJECTIVE: The predominant mechanism driving hyperuricemia in gout is renal uric acid underexcretion; however, the standard urate-lowering therapy (ULT) recommendation is first-line xanthine oxidase inhibitor (XOI), irrespective of the cause of hyperuricemia. This comparative effectiveness clinical trial was undertaken to compare first-line nontitrated low-dose benzbromarone (LDBen) uricosuric therapy to XOI ULT with low-dose febuxostat (LDFeb) in gout patients with renal uric acid underexcretion. METHODS: We conducted a prospective, randomized, single-center, open-label trial in men with gout and renal uric acid underexcretion (defined as fractional excretion of urate <5.5% and uric acid excretion ≤600 mg/day/1.73 m2 ). A total of 196 participants were randomly assigned to receive LDBen 25 mg daily or LDFeb 20 mg daily for 12 weeks. All participants received daily urine alkalization with oral sodium bicarbonate. The primary end point was the rate of achieving the serum urate target of <6 mg/dl. RESULTS: More participants in the LDBen group achieved the serum urate target than those in the LDFeb group (61% compared to 32%, P < 0.001). Rates of adverse events, including gout flares and urolithiasis, did not differ between groups, with the exception of greater transaminase elevation in the LDFeb group (4% for LDBen compared to 15% for LDFeb, P = 0.008). CONCLUSION: Compared to LDFeb, LDBen has superior urate-lowering efficacy and similar safety in treating relatively young and healthy patients with renal uric acid underexcretion-type gout.

Effectiveness of benzbromarone versus febuxostat in gouty patients: a retrospective study.

OBJECTIVES: Benzbromarone and febuxostat use different mechanisms to reduce serum urate. However, the effectiveness of benzbromarone versus febuxostat in reducing serum urate in gouty patients classified with different types of hyperuricaemia remains unclear. METHOD: In this retrospective study from January 1, 2018, to September 30, 2020, subjects were identified if they were newly treated with benzbromarone 25 mg daily or febuxostat 20 mg daily. The subjects were classified into four types according to their 24-h urinary uric acid and fractional excretion of uric acid. The baseline data and follow-up information after 28 ± 3 days of treatment were collected. RESULTS: Seventy-three subjects with gout were finally enrolled. Among them, 50 were treated with benzbromarone. The percent changes in serum urate from the baseline were - 33.71 ± 13.59% and - 29.45 ± 10.62% in the benzbromarone and febuxostat group, respectively, without a significant difference between the groups (P = 0.188). No differences were found between the groups in subjects classified as the renal underexcretion type, combined type, or "normal" type. In patients with eGFR ≥ 70 mL/min/1.73 m2, the rate of serum urate lowering was higher in those treated with benzbromarone than in those treated with febuxostat. Febuxostat treatment significantly lowered serum creatinine from the baseline (P = 0.001). CONCLUSIONS: Benzbromarone 25 mg daily and febuxostat 20 mg daily may have comparable effectiveness in lowering the serum urate among different types of hyperuricaemia. Benzbromarone was more effective than febuxostat in lowering serum urate in subjects with eGFR ≥ 70 mL/min/1.73 m2, while febuxostat had a renal protective effect. Key Points • Benzbromarone 25 mg daily and febuxostat 20 mg daily may have comparable effectiveness in lowering the serum urate in patients with different types of hyperuricaemia. • Benzbromarone 25 mg daily was more effective than febuxostat 20 mg daily in lowering serum urate in subjects with eGFR ≥ 70 mL/min/1.73 m2. • Febuxostat had a renal protective effect after about 1 month treatment.

SGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function.

BACKGROUND AND OBJECTIVES: Sodium-glucose transporter 2 (SGLT2) inhibitor-induced uric acid lowering may contribute to kidney-protective effects of the drug class in people with type 2 diabetes. This study investigates mechanisms of plasma uric acid lowering by SGLT2 inhibitors in people with type 2 diabetes with a focus on urate transporter 1. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an analysis of two randomized clinical trials. First, in the Renoprotective Effects of Dapagliflozin in Type 2 Diabetes study, 44 people with type 2 diabetes were randomized to dapagliflozin or gliclazide for 12 weeks. Plasma uric acid, fractional uric acid excretion, and hemodynamic kidney function were measured in the fasted state and during clamped euglycemia or hyperglycemia. Second, in the Uric Acid Excretion study, ten people with type 2 diabetes received 1 week of empagliflozin, urate transporter 1 blocker benzbromarone, or their combination in a crossover design, and effects on plasma uric acid, fractional uric acid excretion, and 24-hour uric acid excretion were measured. RESULTS: In the Renoprotective Effects of Dapagliflozin in Type 2 Diabetes study, compared with the fasted state (5.3±1.1 mg/dl), acute hyperinsulinemia and hyperglycemia significantly reduced plasma uric acid by 0.2±0.3 and 0.4±0.3 mg/dl (both P<0.001) while increasing fractional uric acid excretion (by 3.2%±3.1% and 8.9%±4.5%, respectively; both P<0.001). Dapagliflozin reduced plasma uric acid by 0.8±0.8 during fasting, 1.0±1.0 in hyperinsulinemic-euglycemic state, and 0.8±0.7 mg/dl during hyperglycemic conditions (P<0.001), respectively, whereas fractional uric acid excretion in 24-hour urine increased by 3.0%±2.1% (P<0.001) and 2.6%±4.5% during hyperinsulinemic-euglycemic conditions (P=0.003). Fractional uric acid excretion strongly correlated to fractional glucose excretion (r=0.35; P=0.02). In the Uric Acid Excretion study, empagliflozin and benzbromarone both significantly reduced plasma uric acid and increased fractional uric acid excretion. Effects of combination therapy did not differ from benzbromarone monotherapy. CONCLUSIONS: In conclusion, SGLT2 inhibitors induce uric acid excretion, which is strongly linked to urinary glucose excretion and is attenuated during concomitant pharmacologic blockade of urate transporter 1. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Renoprotective Effects of Dapagliflozin in Type 2 Diabetes (RED), NCT02682563; SGLT2 Inhibition: Uric Acid Excretion Study (UREX), NCT05210517.

Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update.

This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that further well-designed clinical research is needed to deepen their efficacy and safety profile.

The efficacy and safety of citrate mixture vs sodium bicarbonate on urine alkalization in Chinese primary gout patients with benzbromarone: a prospective, randomized controlled study.

OBJECTIVES: To compare the efficacy and safety of citrate mixture and sodium bicarbonate on urine alkalization in gout patients under benzbromarone treatment. METHODS: A prospective, randomized, parallel controlled trial was conducted among 200 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University. The participants were randomly divided into two groups (1:1), sodium bicarbonate group (3 g/day) and citrate mixture group (7 g/day). All patients were prescribed with 25 mg/day benzbromarone at initiation and maintained at a dose of 50 mg/day. Clinical and biochemical data were collected at each follow-up time point (baseline, weeks 2, 4, 8 and 12). RESULTS: A total of 182 patients completed the 12-week urine alkalization study. The urine pH value of both groups increased significantly from the baseline to the final follow-up time point (sodium bicarbonate group, 5.50-6.00, P < 0.05; citrate mixture group, 5.53-5.93, P < 0.05). While the comparisons regarding urine pH between treatment groups showed no significant differences for each time point. The estimated glomerular filtration rate (eGFR) dropped significantly after 12 weeks' trial in the sodium bicarbonate group (P < 0.01), while it was comparable between baseline and the last follow-up (P > 0.05) in the citrate mixture group. Results of urine analysis showed that the incident rate of occult blood in the sodium bicarbonate group was higher than that in the citrate mixture group (38 vs 24%, P < 0.05), accompanied by a similar occurrence of kidney stones. After 12-week follow-up, the frequency of twice gout flare in the citrate mixture group was significantly lower than that in sodium bicarbonate group (4 vs 12%, P = 0.037). No treatment-emergent adverse events occurred. CONCLUSION: The efficacy of citrate mixture on urine alkalization is comparable to sodium bicarbonate under benzbromarone treatment without significant adverse events. Citrate mixture is superior to sodium bicarbonate in lowering the incidence of urine occult blood and the frequency of gout attacks. TRIAL REGISTRATION: Registered with ChiCTR (http://www.chictr.org.cn), No. ChiCTR1800018518.

Randomized, Open-Label, Cross-Over Comparison of the Effects of Benzbromarone and Febuxostat on Endothelial Function in Patients with Hyperuricemia.

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.

Effects of Conventional Uric Acid-Lowering Therapy on Monosodium Urate Crystal Deposits.

OBJECTIVE: Few studies have systematically and quantitatively addressed the impact of urate-lowering therapy on monosodium urate (MSU) deposits. This study was undertaken to analyze the effect of lifestyle measures and conventional urate-lowering therapy on MSU deposits in patients with gout. METHODS: In this prospective study, subjects with gout according to the American College of Rheumatology/European League Against Rheumatism classification criteria and presence of MSU deposits seen on dual-energy computed tomography (DECT) scans received either lifestyle intervention or conventional urate-lowering therapy for a mean period of 18 months before a follow-up DECT scan. Detected MSU deposits were quantified by volumetric measurement and validated by semiquantitative scoring, and baseline and follow-up measurements were compared. RESULTS: Baseline and follow-up DECT scans were available for all 83 subjects. Six subjects discontinued treatment, and 77 subjects underwent a lifestyle intervention (n = 24) or were treated with allopurinol (n = 29), febuxostat (n = 22), or benzbromarone (n = 2) over the entire observation period. The mean serum uric acid (UA) level decreased from 7.2 to 5.8 mg/dl in the overall population. In patients who discontinued treatment, no change in MSU deposits or serum UA levels was observed. The burden of MSU deposits significantly decreased in patients undergoing lifestyle intervention (MSU volume P = 0.007; MSU score P = 0.001), and in patients treated with allopurinol (MSU volume and score P < 0.001) or febuxostat (MSU volume P < 0.001; MSU score P = 0.001). No significant decline in MSU deposits was noted in patients who discontinued treatment. CONCLUSION: These data show that lifestyle intervention and xanthine oxidase inhibitors significantly decrease the MSU deposit burden. Hence, conventional gout therapy not only lowers serum UA levels, but also reduces pathologic MSU deposits.