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Objectives To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations for gout flares. Methods We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment and re-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation. Results One hundred and nineteen and 108 patients, respectively, were hospitalized for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n  = 94 and n  = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio [aOR] 11.5; 95% CI 4.36, 30.5; P  < 0.001). After implementation, more patients achieved a serum urate ≤360 μmol/l within 6 months of discharge (10.6% pre-implementation vs 26.8% post-implementation; aOR 3.04; 95% CI 1.36, 6.78; P  = 0.007). The proportion of patients re-hospitalized for flares was 14.9% pre-implementation vs 9.3% post-implementation (aOR 0.53; 95% CI 0.22, 1.32; P  = 0.18). Conclusion Over 90% of patients were initiated on ULT after implementing a strategy to optimize hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalizations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalized gout patients to achieve urate targets, closer primary–secondary care integration is still needed. [ABSTRACT FROM AUTHOR]

Gout is characterized by monosodium urate (MSU) crystal deposition secondary to hyperuricemia. Gout is associated with metabolic syndrome (MetS) and its related comorbid conditions such as cardiovascular disease (CVD). Major advances have been made in the comprehension of the link between MetS and gout. Despite observational studies suggesting an association between MetS-related conditions and hyperuricemia, there is no proof of causality. Most studies using Mendelian randomization did not find hyperuricemia as a causal factor for MetS-related conditions. In contrast, these conditions were found associated with hyperuricemia, which suggests a reverse causality. Among patients with gout, this high CVD risk profile implies the need for systematic screening for MetS-related conditions. Most international guidelines recommend systematic screening for and care of CVD and related risk factors in patients with gout. Some anti-hypertensive agents, such as losartan and calcium channel blockers, are able to decrease serum urate (SU) levels. However, there are potential interactions between gout management therapies and the treatment of metabolic diseases. Some data suggest that anti-inflammatory drugs used for gout flare treatment, such as colchicine or canakinumab, might have benefits for CVD. Regarding the impact of urate-lowering therapies on CVD risk, recent studies found a similar CVD safety profile for allopurinol and febuxostat. Finally, sodium-glucose cotransporter-2 inhibitors are promising for gout because of their ability to decrease SU levels and risk of recurrent flares. In this review, we focus on the clinical challenge of managing MetS in patients with gout, particularly older patients with co-medications. [ABSTRACT FROM AUTHOR]

ObjectiveGout is associated with a higher risk of fracture; however, findings on the associations of hyperuricemia and urate-lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e.,

ObjectiveThe American College of Rheumatology's (ACR) 2020 guidelines for the management of gout recommend using a treat-to-target approach to lower serum urate (SU). Using the ACR's Rheumatology Informatics System for Effectiveness registry, we examined the use of a treat-to-target approach among gout patients receiving long-term urate-lowering therapy (ULT) and followed longitudinally by rheumatologists.MethodsIncluded patients had one or more diagnoses for gout in 2018-2019 and continuous use of ULT for ≥12 months. We assessed the proportions of patients with SU monitoring and, among those tested, who achieved SU

ImportancePrescription drug prices are a leading concern among patients and policy makers. There have been large and sharp price increases for some drugs, but the long-term implications of large drug price increases remain poorly understood.ObjectiveTo examine the association of the large 2010 price increase in colchicine, a common treatment for gout, with long-term changes in colchicine use, substitution with other drugs, and health care use.Design, setting, and participantsThis retrospective cohort study examined MarketScan data from a longitudinal cohort of patients with gout with employer-sponsored insurance from 2007 through 2019.ExposuresThe US Food and Drug Administration's discontinuation of lower-priced versions of colchicine from the market in 2010.Main outcomes and measuresMean price of colchicine; use of colchicine, allopurinol, and oral corticosteroids; and emergency department (ED) and rheumatology visits for gout in year 1 and over the first decade of the policy (through 2019) were calculated. Data were analyzed between November 16, 2021, and January 17, 2023.ResultsA total of 2 723 327 patient-year observations were examined from 2007 through 2019 (mean [SD] age of patients, 57.0 [13.8] years; 20.9% documented as female; 79.1% documented as male). The mean price per prescription of colchicine increased sharply from $11.25 (95% CI, $11.23-$11.28) in 2009 to $190.49 (95% CI, $190.07-$190.91) in 2011, a 15.9-fold increase, with the mean out-of-pocket price increasing 4.4-fold from $7.37 (95% CI, $7.37-$7.38) to $39.49 (95% CI, $39.42-$39.56). At the same time, colchicine use declined from 35.0 (95% CI, 34.6-35.5) to 27.3 (95% CI, 26.9-27.6) pills per patient in year 1 and to 22.6 (95% CI, 22.2-23.0) pills per patient in 2019. Adjusted analyses showed a 16.7% reduction in year 1 and a 27.0% reduction over the decade (P

Objectives Frequent gout attacks in the initial introduction of urate-lowering therapy (ULT) are significant causes of poor drug adherence and ULT discontinuation. Initial low-dose urate-lowering drugs may be effective in reducing gout flares, however robust evidence is sparse. The aim of this study was therefore to assess the association of initial dose urate-lowering drugs with gout flares in adult males with gout during the initial introduction of ULT. Methods This cohort study obtained data on consecutive gout patients from a single-centre gout cohort study from August 2017 to October 2020. A standard questionnaire was applied to collect demographic and clinical information, and biochemical parameters were tested on the same day. The primary endpoint was to estimate the association of initial dose febuxostat with gout flares, using Cox hazard models with inverse probability of treatment weighting (IPTW). Results A total of 582 gout patients were included in this study. During the 6-week follow-up, 71 (12.2%) patients suffered gout flares. In the main analysis using Cox hazard models with IPTW, compared with colchicine prophylaxis, initial low-dose febuxostat alone had no statistical significance with the increased risk of gout flares [hazard ratio (HR) 1.26; 95% CI 0.58, 2.72], while initial high-dose febuxostat was associated with an increased risk of gout flares (HR 3.08; 95% CI 1.34, 7.07). Conclusions This observational study demonstrated that initial low-dose febuxostat was equally effective in preventing gout flares as colchicine prophylaxis, while initial high-dose febuxostat alone was associated with an increased risk of gout flares. [ABSTRACT FROM AUTHOR]

Allopurinol is a commonly prescribed agent in the urologic population for the prevention of urinary stones. Although generally well-tolerated, several serious potential side effects can occur with its use. Allopurinol hypersensitivity syndrome (AHS), in particular, is a relatively rare but potentially life-threatening complication. With the observed increase in urinary stone disease, especially those of uric acid composition, it is likely that the use of allopurinol will increase. Urologists play an important role in the assessment and medical management of patients with urinary stones, thus a greater awareness of the potential adverse events associated with allopurinol use, especially AHS, is important, as well as strategies that can minimize such risks. Herein, we review the potential adverse effects of allopurinol. In addition, the results of a comprehensive review of the current literature on AHS will be presented, highlighting those patients at highest risk, reviewing the genetic susceptibility testing currently available, and providing guidance on best practices when allopurinol therapy is being considered. [ABSTRACT FROM AUTHOR]

Gout is a common and treatable chronic disease of monosodium urate crystal deposition. It is experienced as extremely painful episodes of joint inflammation that impact all aspects of the person's life. This Clinical Perspectives article provides an update on gout diagnosis, medications and strategies to improve the quality of gout care. [ABSTRACT FROM AUTHOR]

Objective: Using trial data comparing treat‐to‐target allopurinol and febuxostat in gout, we examined participant characteristics associated with serum urate (SU) goal achievement. Methods: Participants with gout and SU ≥6.8 mg/dL were randomized to allopurinol or febuxostat, titrated during weeks 0 to 24, and maintained weeks 25 to 48. Participants were considered to achieve SU goal if the mean SU from weeks 36, 42, and 48 was <6.0 mg/dL or <5 mg/dL if tophi were present. Possible determinants of treatment response were preselected and included sociodemographics, comorbidities, diuretic use, health‐related quality of life (HRQoL), body mass index, and gout measures. Determinants of SU response were assessed using multivariable logistic regression with additional analyses to account for treatment adherence. Results: Of 764 study participants completing week 48, 618 (81%) achieved SU goal. After multivariable adjustment, factors associated with a greater likelihood of SU goal achievement included older age (adjusted odds ratio [aOR] 1.40 per 10 years), higher education (aOR 2.02), and better HRQoL (aOR 1.17 per 0.1 unit). Factors associated with a lower odds of SU goal achievement included non‐White race (aORs 0.32–0.47), higher baseline SU (aOR 0.83 per 1 mg/dL), presence of tophi (aOR 0.29), and the use of diuretics (aOR 0.52). Comorbidities including chronic kidney disease, hypertension, diabetes, and cardiovascular disease were not associated with SU goal achievement. Results were not meaningfully changed in analyses accounting for adherence. Conclusions: Several patient‐level factors were predictive of SU goal achievement among patients with gout who received treat‐to‐target urate‐lowering therapy (ULT). Approaches that accurately predict individual responses to treat‐to‐target ULT hold promise in facilitating personalized management and improving outcomes in patients with gout. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is an important cause of mortality in older patients. In addition to the traditional risk factors for cardiovascular disease, hyperuricemia has been increasingly associated with an elevated risk of cardiovascular disease. Uric acid itself has several unfavorable effects on the cardiovascular system, and hyperuricemia can lead to the development of gout. Gout is the most prevalent inflammatory rheumatic disease. Older patients with gout have an increased risk of cardiovascular morbidity and mortality due to an increased prevalence of traditional risk factors, as well as the inflammatory burden of gout activity. As the prevalence of traditional risk factors and the prevalence of both hyperuricemia and gout are increasing in older adults, cardiovascular risk management in these patients is very important. This risk management consists of, on the one hand, treatment of individual traditional risk factors and, on the other hand, of urate lowering, thereby decreasing inflammatory burden of gout. However, there is insufficient evidence to conclude that urate-lowering therapy reduces the risk of cardiovascular events. Moreover, from a cardiovascular point of view, there is no preference for one urate lowering drug over another in patients with gout, nor is there enough evidence to support a preference in patients with gout with increased cardiovascular risk. Personalized treatment in older patients with gout should be aimed at optimizing serum uric acid levels, as well as targeting traditional cardiovascular risk factors. Further prospective randomized trials are needed to support the hypothesis that urate lowering reduces cardiovascular risk in older patients with gout. [ABSTRACT FROM AUTHOR]

ObjectiveLinked metabolic and cardiovascular comorbidities are prevalent in hyperuricemia and gout. For mechanistic insight into impact on inflammatory processes and cardiometabolic risk factors of xanthine oxidase inhibitor urate-lowering therapy (ULT) titration to target, we performed a prospective study of gout serum metabolomes from a ULT trial.MethodsSera of gout patients meeting the 2015 ACR/EULAR gout classification criteria (n = 20) and with hyperuricemia were studied at time zero and weeks 12 and 24 of febuxostat or allopurinol dose titration ULT. Ultrahigh performance liquid chromatography-tandem mass spectroscopy acquired the serum spectra. Data were assessed using the Metabolon and Metaboloanalyst software. Lipolysis validation assays were done in febuxostat and/or colchicine-treated 3T3-L1 differentiated adipocytes.ResultsSerum urate decreased from time zero (8.21 ±1.139 SD) at weeks 12 (5.965 ± 1.734 SD) and 24 (5.655 ±1.763 SD). Top metabolites generated by changes in nucleotide and certain amino acid metabolism and polyamine pathways were enriched at 12 and 24 weeks ULT, respectively. Decreases in multiple fatty acid metabolites were observed at 24 weeks, linked with obesity. In cultured adipocytes, febuxostat significantly decreased while colchicine increased the lipolytic response to β-adrenergic-agonism or TNF.ConclusionMetabolomic profiles linked xanthine oxidase inhibitor-based ULT titration to target with reduced serum free fatty acids. In vitro validation studies revealed that febuxostat, but not colchicine, reduced lipolysis in cultured adipocytes. Since soluble urate, xanthine oxidase inhibitor treatment, and free fatty acids modulate inflammation, our findings suggest that by suppressing lipolysis, ULT could regulate inflammation in gout and comorbid metabolic and cardiovascular disease.

Several urate‐lowering drugs have been linked to muscle injury. This study investigated the association of oral urate‐lowering drugs with the risk of muscle injury by performing a network meta‐analysis of randomized and non‐randomized controlled trials. A systematic search of MEDLINE, via PubMed, the ClinicalTrials.gov website, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant studies with a primary outcome of "all muscle injuries." A random‐effects model was used to perform a frequentist network meta‐analysis to estimate whether there was significant heterogeneity among the studies. In total, 32 studies including 28,327 participants with 2694 (9.5%) "all muscle injuries" were assessed, and the overall risk of bias was judged to be low to moderate. No statistically significant differences were found between placebo and 6 urate‐lowering therapies: allopurinol (risk ratio, RR, 1.05; 95% confidence interval, 95%CI, 0.63‐1.73), febuxostat (RR 1.10, 95%CI 0.71‐1.70), lesinurad (RR 7.00, 95%CI 0.31‐160.36), lesinurad concomitant with allopurinol (RR 0.85, 95%CI 0.34‐2.11), lesinurad concomitant with febuxostat (RR 1.97, 95%CI 0.55‐7.03), and topiroxostat (RR 0.99, 95%CI 0.37‐2.65). The findings suggest that there is little need to consider the risk of muscle injury when using urate‐lowering drugs in the clinical setting. [ABSTRACT FROM AUTHOR]

The article focuses on advocating for effective patient care in managing refractory pain during inpatient rehabilitation. Topics include the challenges of managing polyarticular gout in a rehabilitation setting, the diagnostic complexities involving joint swelling and pain, and the specialized pharmacological management required for acute gout flares.

Objectives: To assess whether the extent of monosodium urate (MSU) crystal deposition estimated by ultrasound could predict renal and cardiometabolic events during urate‐lowering therapy (ULT). Methods: A prospective study on gout patients from two referral centers initiating ULT who underwent baseline ultrasound and were followed for 1 year. Ultrasound scans assessed six joints for double‐contour (DC) signs and tophi. A five‐point change (mL/min/1.73 m2) in the glomerular filtration rate at month 12 (M12) was considered significant. Outcomes of interest were renal function degraded versus improved and a composite cardiometabolic outcome (new hypertension, diabetes, atherosclerotic disease, and cardiovascular death). Homogeneity analyses and Cox regression models were performed. Results: One hundred sixty patients were recruited. At baseline, 81.1% of patients (n = 129) showed sonographic tophi with a mean number of 1.4 joints (±1.3) with a DC sign. At M12, 18 patients (11.3%) were lost to follow‐up. The serum urate (SU) target (<6.0 mg/dL) was reached in 86 patients (69.9%). Regarding renal function, 15.9% of patients showed improvement, while in 31.0% it degraded. Fourteen new cardiometabolic events occurred in 12 patients. Neither the DC sign nor tophi showed any significant impact on the outcomes of interest. Baseline SU level was higher in those with renal improvement but not with renal decline, while achieving the SU target protected against new cardiometabolic events (HR = 0.2; 95% CI: 0.05–0.81). Conclusions: Sonographic MSU crystal burden was unhelpful in predicting renal and cardiometabolic events during the first year of ULT. Reaching the SU target prevented cardiometabolic events, while its benefit in preserving/improving renal function is unclear. [ABSTRACT FROM AUTHOR]

Benjamin Franklin, one of the founding fathers of the United States, was not just a politician and a political philosopher but an inventor with a scientific temperament. He was overweight and likely suffered from the consequences of metabolic syndrome including gout. He woke up with a gout attack on October 22, 1780 and wrote the "Dialogue Between Franklin and the Gout." His observations on the risk factors for gout are re-examined in the modern context 243 years later [ABSTRACT FROM AUTHOR]

Sungkai plant (Peronema canescens Jack.) is an herbal plant that people widely use traditionally to treat various diseases. Sungkai is proven to have immunostimulant, antihyperuricemia, and antibacterial activities. Due to its widespread use and to ensure its safety, it is necessary to evaluate its toxicity. This study aimed to determine the effect of variations in dose and duration of administration of ethanol extract of Sungkai leaves (Peronema canescens Jack.) on SGPT and SGOT levels in male white mice. Thirty-six mice divided into four groups (a control group and three treatment groups) of nine each were used for this study. The control group received 0.5% Na CMC suspension, and the treatment groups (II-IV) were given the ethanol extract suspension of Sungkai leaves (Peronema canescens Jack.) at a dose of 200, 400 and 800 mg/kg BW p.o, respectively. The extracts were administered daily to the experimental animals for 7, 14, and 21 days. SGPT and SGOT levels were examined on days 8, 15 and 22 using a 5010 v5+ photometer. Data analysis was performed using the SPPS with a two-way ANOVA test based on variations in dose and duration of administration. The results of this study indicate that the ethanol extract of Sungkai leaves has no significant effect on SGPT and SGOT levels (p>0.05) based on variations in the dose and duration of administration. [ABSTRACT FROM AUTHOR]

Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper.

This study aims to assess urate-lowering therapy adherence and the relationship with medication beliefs, self-efficacy, depression, anxiety, and COVID−19 pandemic-related concerns in Chinese gout patients during the COVID−19 outbreak. 101 gout patients receiving urate-lowering therapy were involved to evaluate adherence, medication beliefs, self-efficacy, depression, anxiety, and COVID−19 pandemic-related concerns via a mobile app-based questionnaire. Statistical analysis was performed using SPSS 22.0. A total of 101 valid responses were included in the statistical analysis. The results showed that, the rate of adherence to urate-lowering therapy during the COVID−19 outbreak was 22.8% in Chinese patients with gout, higher than that in normal times (9.6%). Compared to the adherent group, non-adherent gout patients had shorter disease duration, lower self-efficacy, lower necessity about urate-lowering therapy score, higher concerns about urate-lowering therapy score, and smaller necessity-concerns differential. Depression and anxiety rates (3.0% and 5.0%, respectively) during the COVID−19 break were lower than that in normal times. Additionally, depression, anxiety, as well as COVID−19 pandemic-related concerns (27.7%) were not related to urate-lowering therapy adherence. In conclusion, adherence rate to urate-lowering therapy in Chinese gout patients during the COVID−19 outbreak was 22.8%, higher than normal times, but still very poor. Except for a little concern about being more susceptible to the virus, patients' mental state is relatively good. While the country puts great efforts into COVID−19 prevention and control, attention must also be paid to the medication management of patients with chronic diseases such as gout. [ABSTRACT FROM AUTHOR]

Objective: To assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]). Methods: Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8‐mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent‐to‐treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU‐monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. Results: Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%‐44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%‐44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. Conclusion: Twelve‐month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the safety and efficacy of the nonpurine xanthine oxidase inhibitor tigulixostat for lowering serum urate level in gout patients with hyperuricemia. Methods: We conducted a multicenter, phase II, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐finding trial. After screening, gout patients with hyperuricemia were randomly assigned, after appropriate washout, to receive daily oral administration of 50 mg, 100 mg, or 200 mg of tigulixostat, or placebo for 12 weeks. Colchicine gout flare prophylaxis was administered to all patients. The primary end point was the proportion of patients with a serum urate level <5.0 mg/dl at week 12. Results: A total of 143 patients were randomized to receive tigulixostat 50 mg (n = 34), 100 mg (n = 38), or 200 mg (n = 37), or placebo (n = 34). A significantly greater proportion of patients in the tigulixostat groups achieved the target serum urate level <5.0 mg/dl at week 12 (47.1% in the 50 mg group, 44.7% in the 100 mg group, and 62.2% in the 200 mg group) compared to the placebo group (2.9%) (P < 0.0001). The mean percentage change in serum urate level from baseline was also significantly greater in the tigulixostat groups (−38.8% to −61.8%) than in the placebo group at all time points (P < 0.0001). The rate of gout flares requiring rescue treatment ranged from 9.4% to 13.2% in the tigulixostat and placebo groups. The incidence of adverse events was 50.0% to 56.8% across all groups, and their severity was mild or moderate. Conclusion: Tigulixostat significantly lowered serum urate compared to placebo at all doses studied with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Objective Gout flares during urate-lowering therapy (ULT) initiation are common, but predictors of these flares are poorly understood. The aim of this study was to determine whether serum CA72-4 is an independent predictor for gout flares during ULT initiation. Methods A prospective cohort study was conducted between March 2021 and January 2022. Men with gout, at least one gout flare in the past year, and at least three serum CA72-4 measurements in the previous six months were enrolled. Participants were grouped according to their highest recorded serum CA72-4 levels (above or within the normal range). All participants took oral febuxostat 20 mg daily without flare prophylaxis therapy, and attended face-to-face visits every four weeks until 24 weeks. The incidence of gout flare was compared between the two groups. Backward stepwise logistic regression analyses were used to identify risk factors associated with flares. Receiver operating characteristic curve analysis was used to evaluate prediction efficacy. Results A total of 193 completed the study (79 with high CA72-4; 114 with normal CA72-4). The cumulative incidence of at least one gout flare was 48.1% (62.1% in the high CA72-4 group, 38.4% in the normal CA72-4 group, P  = 0.001), and recurrent (≥2) flares was 33.0% (47.1% in the high CA72-4 group, 23.2% in the normal CA72-4, P  < 0.001). High CA72-4, disease duration, intra-articular tophus size, glucose, high-density lipoprotein-cholesterol and ESR were independent risk factors for gout flares. Serum CA72-4 alone predicted recurrent flares with an area under the curve of 0.63 (95% CI = 0.54, 0.71), and 0.78 (95% CI = 0.71, 0.85) when combined with other independent variables. Conclusion High serum CA72-4 predicts the risk of gout flares during ULT initiation. Trial registration ChiCTR; https://www.chictr.org.cn/ ; ChiCTR2100043573. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the relative efficacy and safety of pharmacologic antiinflammatory interventions for gout flares. METHODS: We searched Ovid Medline, Embase, and Cochrane library for randomized controlled trials (RCTs) that compared pharmacologic antiinflammatory treatment of gout flares. We conducted a network meta-analysis (NMA) using a frequentist framework and assessed the certainty of evidence and made conclusions using the Grading of Recommendations Assessment, Development, and Evaluation for NMA. RESULTS: In the 30 eligible RCTs, canakinumab provided the highest pain reduction at day 2 and at longest follow-up (mean difference relative to acetic acid derivative nonsteroidal antiinflammatory drugs [NSAIDs] -41.12 [95% confidence interval (95% CI) -53.36, -29.11] on a 0-100 scale at day 2, and mean difference -12.84 [95% CI -20.76, -4.91] at longest follow-up; both moderate certainty; minimum important difference -19). Intravenous or intramuscular corticosteroids were inferior to canakinumab but may be better than the other commonly used interventions (low to very low certainty). For joint tenderness, canakinumab may be the most effective intervention at day 2. Acetic acid derivative NSAIDs improved joint swelling better than ibuprofen NSAIDs at day 2 (mean difference -0.29 [95% CI -0.56, -0.02] on a 0-4 scale; moderate certainty) and improved patient global assessment (PtGA) greater than ibuprofen NSAIDs at the longest follow-up (mean difference -0.44 [95% CI -0.86, -0.02]; moderate). CONCLUSION: Canakinumab may be superior to other alternatives and intravenous or intramuscular corticosteroids may be the second best in pain reduction. Acetic acid derivative NSAIDs may be superior to ibuprofen NSAIDs in improving joint swelling and PtGA.

In order to highlight the activities of bioactive compounds present in the stem of sweet cherries, four different cultivars (Van, Burlat, Napoleon, and Cœur pigeon) were collected in Sefrou city in Morocco and were studied. Several assays were performed for this purpose, such as the quantification of phenolic compounds (TPC, TFC, and CTC) and the evaluation of the antioxidant activity using DPPH, ABTS, and FRAP assays. The phenolic profile of each extract was characterized by UHPLC-DAD/MS analysis. The antidiabetic (α-amylase inhibition) and antigout (xanthine oxidase inhibition) activities were also investigated. The results showed high levels of phenolic compounds, with the values of 340 ± 12.06, 244 ± 10.20, 232 ± 5.07, and 19 ± 3.10 mg gallic acid equivalent/g extract for the cultivars Napoleon, Coeur de pigeon, Van, and Burlat, respectively. According to the same order, the flavonoids showed amounts of 34.31 ± 2.08, 23.75 ± 1.02, 24.37 ± 1.20, and 23.31 ± 0.90 mg (rutin equivalent) RE/g extract. These values were correlated with the results of the antioxidant assays, where the Napoleon cultivar proved to be the most potent using the DPPH (IC50 = 2.51 µg/mL) and ABTS (IC50 = 55.38 µg/mL) assays. The phenolic profile of each extract resulted in the identification of twenty-two compounds belonging to five distinct groups. The major phenolic compounds identified were sakuranetin and dihydrowgonin with their glucosides. Antidiabetic activity assays showed that only stem extracts from Burlat and Napoleon cultivars were able to inhibit the α-amylase enzyme with values of 85.57 ± 1.09% and 68.01 ± 3.52%, respectively. All stem extracts proved their ability to inhibit the xanthine oxidase enzyme which is directly linked to the gout disease, with a high value for Van cultivar (40.63 ± 2.37%). These new findings could provide new opportunities for the valorization of cherry stems for the pharmaceutical application of their active phytochemicals. [ABSTRACT FROM AUTHOR]

The acknowledgement of the significant role of inflammation in the pathophysiology of atherosclerosis has led to the investigation of anti-inflammatory therapies for the management of cardiovascular disease (CVD). Among these are colchicine as well as other pharmacotherapies used to treat gout (e.g. allopurinol, febuxostat). While clinical trial data support the consideration of colchicine for the secondary prevention of CVD, the same cannot be said for allopurinol and febuxostat. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the available evidence from clinical trials on the efficacy of gout medicines against COVID‐19. Design: Systematic review and Meta‐analysis. Methods: We are systematically searching five databases [PubMed, Embase, CT.gov, ICTRP, CINAHL (EBSCO)]. We are following the PRISMA statement and the EPOC guidelines. The meta‐analysis will be conducted using Revman‐5.4.1 from Cochrane collaboration, UK. This review's protocol was also registered in PROSPERO, University of York, UK (CRD42022299718). Results: In this meta‐analysis, we plan to give a conclusive overview of the available evidence on the efficacy of the medications used to manage gout in reducing COVID‐19 mortality, ICU admission, ventilation rate and hospitalization duration. If the results were positive, these drugs would greatly add to the scarce treatment options against COVID‐19. Furthermore, these drugs might provide an excellent alternative to inconvenient and expensive drugs. Additionally, most of these drugs have a well‐established safety profile for use during nursing, making them a much safer option for nursing mothers with COVID‐19. [ABSTRACT FROM AUTHOR]

BackgroundIn gout, long-term urate-lowering therapy (ULT) promotes dissolution of tissue urate crystal deposits. However, no studies using combined xanthine oxidase inhibition and uricosuric ULT have focused on clinical outcomes or adverse events (AEs) beyond 12 months of therapy. Our objective in the present study was to examine efficacy and long-term safety in patients with tophaceous gout receiving febuxostat plus lesinurad as combination therapy.MethodsPatients receiving combined lesinurad and febuxostat in the 12-month core CRYSTAL study continued at the same doses in the extension study ("200CONT", "400CONT"), whereas those receiving only febuxostat 80 mg were randomized to lesinurad 200 or 400 mg with febuxostat ("200CROSS", "400CROSS"). The primary endpoint was the proportion of patients experiencing complete resolution (CR) of at least one target tophus by extension month (EM) 12. The key secondary endpoint was mean rate of gout flares requiring treatment from the end of EM 2 to the end of EM 12. Secondary endpoints included reduction in the sum of areas for all target tophi. Safety assessments included AEs and laboratory data for the entire extension study (median length of lesinurad exposure, 800 days).ResultsOf 235 patients completing the core study, 196 (83.4%) enrolled in the extension: 200CONT (n = 64), 200CROSS (n = 33), 400CONT (n = 65), and 400CROSS (n = 34). At EM 12, 59.6%, 43.5%, 66.7%, and 50.0% of patients, respectively, had CR of at least one target tophus. The sum of areas for all target tophi was reduced by 76.4%, 58.1%, 77.5%, and 62.8%, respectively. The adjusted mean (SE) rates of gout flares requiring treatment from the end of EM 2 to the end of EM 12 were 0.6 (0.19), 1.3 (0.48), 0.2 (0.08), and 1.9 (0.93), respectively. Target sUA

The objective of the present study was to determine the acute and subacute toxicity profile of a polyherbal formulation called "Goubion" in addition to the in vivo antihyperuricemic study using fructose-induced hyperuricemia. Goubion is a combination of Colchicum autumnale (tuber), Tribulus terresteris (fruit), Vitex negundo (leaves), Smilax chinensis (root), Glycyrrhiza glabra (root), and Curcuma amada (rhizome). The acute toxicity study revealed no signs of mortality and morbidity at a single dose of 2000 mg/kg. Similarly, the results of the subacute repeated dose toxicity study exhibited no signs of mortality at any of the doses. However, significant changes in hematological, biochemical, and renal parameters were recorded at the dose of 60 mg/kg. Antihyperuricemic activity was tested at the dose of 15 mg/kg and 20 mg/kg of Goubion, respectively against 5 mg/kg Allopurinol. Based on the antihyperuricemic study, we infer that the Goubion has a significant hypouricemic action, as it remarkably decreased the elevated uric acid levels. The results also suggest the potential inhibitory capability of Goubion on xanthine oxidase dehydrogenase might be the mechanism behind the hypouricemic effect. [ABSTRACT FROM AUTHOR]

Objective: To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo‐controlled, double‐blind trial. Methods: This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate <40 ml/minute/1.73 m2. Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80% of visits during weeks 20–24). Efficacy was evaluated in all randomized patients (intent‐to‐treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose. Results: A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between‐group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P < 0.0001 for between‐group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P < 0.001). Antidrug antibody positivity was also lower in the MTX group. Conclusion: MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX. [ABSTRACT FROM AUTHOR]

SHR4640 is a novel, selective urate reabsorption inhibitor. As the mode of action of SHR4640 differs from that of a xanthine oxidase inhibitor, such as febuxostat, coadministration of these drugs may be a treatment option for patients with primary hyperuricemia. We assessed the potential drug-drug interaction between SHR4640 and febuxostat. In this single-center, open-label, randomized, drug-drug interaction study, subjects received 80 mg febuxostat or 10 mg SHR4640 alone daily in the first week, whereas during the second week a combination of SHR4640 and febuxostat was administered daily to all subjects. Plasma concentrations of SHR4640 and febuxostat were analyzed. We compared their pharmacokinetic and pharmacodynamic parameters and assessed both safety and tolerability. Compared with febuxostat alone, the geometric mean ratios (90%CIs) of the maximum concentration (Cmax) and the area under the plasma concentration-time curve over the dosing interval t (AUC0-t) for febuxostat after coadministration were 1.284 (1.016 to 1.621) and 0.984 (0.876 to 1.106), respectively. The geometric mean ratios (90%CIs) of Cmax and AUC0-t for SHR4640 after coadministration compared with SHR4640 alone were 0.910 (0.839 to 0.988) and 0.929 (0.893 to 0.966), respectively. Febuxostat had no effect on SHR4640 pharmacokinetic parameters, as the 90%CIs of the geometric mean ratios were all within the range of 0.80 to 1.25. The coadministration of febuxostat and SHR4640 was well tolerated. The coadministration of SHR4640 with febuxostat was not associated with any clinically relevant pharmacokinetic drug interactions. SHR4640 combined with febuxostat had a synergistic effect on reducing uric acid in the pharmacodynamics, with the AUC decreasing from 7440 to 3170 h µmol/L compared with febuxostat alone and from 5730 to 2960 h µmol/L compared with SHR4640 alone. [ABSTRACT FROM AUTHOR]

ObjectiveLesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.MethodsSafety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).ResultsIn the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.ConclusionAt the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.

Objectives Pegloticase rapidly lowers serum urate in uncontrolled/refractory gout patients, with ≥1 tophus resolution in 70% of pegloticase responders and 28% of non-responders. Dual-energy computed tomography (DECT) non-invasively detects MSU deposition, including subclinical deposition, quantifies MSU volumes and depicts bone erosions. This report presents DECT findings in MIRROR open-label trial participants receiving pegloticase+MTX co-therapy. Methods Serial DECT scans were obtained during pegloticase (8 mg biweekly infusions)+oral MTX (15 mg/week) co-therapy. Bilateral hand/wrist, elbow, foot/ankle and knee images were analysed with default post-processing settings. MSU volumes were quantified and bone erosions were identified and evaluated for remodelling (decreased size, sclerosis, new bone formation). DECT and physical examination findings were compared. Results 2 patients underwent serial DECT. Patient 1 (44-year-old male) completed 52 weeks of pegloticase+MTX co-therapy (26 infusions). Baseline examination detected 4 tophus-affected joints while DECT identified 73 MSU-affected joints (total MSU volume: 128.76 cm3). At end-of-treatment, there were no clinically-affected joints and 4 joints with DECT-detected MSU deposition. MSU volume decreased by 99% and bone erosion remodelling was evident. Patient 2 (51-year-old male) had 10 weeks of therapy (5 infusions), discontinuing because of urate-lowering response loss. Baseline examination detected 7 tophus-affected joints while DECT identified 55 MSU-affected joints (total MSU volume: 59.20 cm3). At end-of-treatment, there were 5 clinically affected joints and 42 joints with DECT-detected MSU deposition. MSU volume decreased by 58% and bone erosion remodelling was evident. Conclusion DECT detected subclinical MSU deposition and quantified changes over time. Rapid tophus resolution and bone erosion remodelling occurred during pegloticase+MTX co-therapy. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03635957. [ABSTRACT FROM AUTHOR]

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, concurrent medications, 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. [ABSTRACT FROM AUTHOR]

Aims/Introduction: This study aimed to investigate the effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on new prescriptions of drugs, including antihypertensives, antigout/antihyperuricemics and antidyslipidemics, for the treatment of lifestyle‐related diseases in Japanese patients with diabetes mellitus using the JMDC Claims Database. Materials and Methods: Patients with type 2 diabetes mellitus who were newly treated with SGLT2i or other oral antidiabetic drugs and had not been prescribed any antihypertensives, antigout/antihyperuricemics or antidyslipidemics for at least 1 year were extracted from the database. Using propensity score calibration matching (1:1), we assessed the proportion of patients who started the aforementioned concomitant medications within 2 years, and the risk ratio of SGLT2i to other antidiabetic medication groups was calculated. Results: In 856,796 patients with diabetes mellitus, 734, 1,197 and 703 propensity score calibration‐matched patients in each group were analyzed for the prescription of antihypertensives, antigout/antihyperuricemics and antidyslipidemics, respectively. The new prescriptions of antihypertensives and antigout/antihyperuricemics were lower in the SGLT2i group than those in the other oral antidiabetic drug group (risk ratio 0.66 and 0.37, respectively), whereas those of antidyslipidemics were more common in the SGLT2i group (risk ratio 1.43). Conclusions: New prescriptions of antihypertensives or antigout/antihyperuricemics were lower for patients taking SGLT2i than those taking other oral antidiabetic drugs, probably due to a reduction of blood pressure and uric acid levels by SGLT2i. The more frequent prescriptions of antidyslipidemics might partially reflect a moderate increase in low‐density lipoprotein cholesterol levels as a result of sodium–glucose cotransporter 2 inhibition. [ABSTRACT FROM AUTHOR]

Herpetospermum pedunculosum seeds also known as Herpetospermum caudigerum Wall. is the mature seed of the Herpetospermum pedunculosum (Ser.) C. B. Clarke,Cucurbitaceae. Modern pharmacological studies have shown that H. pedunculosum has hepatoprotective, anti-inflammatory, anti-gout and antibacterial pharmacological activities. The biologically active chemical components include lignin compounds such as Herpetin, Herpetetrone, Herpetoriol and so on. The natural product displays considerable skeletal diversity and structural complexity, offering significant opportunities for novel drug discovery. Based on the multi-omics research strategy and the 'gene-protein-metabolite' research framework, the biosynthetic pathway of terpenoids and lignans in H. pedunculosum has has been elucidated at multiple levels. These approaches provide comprehensive genetic information for cloning and identification of pertinent enzyme genes. Furthermore, the application of multi-omics integrative approaches provides a scientific means to elucidate entire secondary metabolic pathways. We investigated the biosynthetic pathways of lignin and terpene components in H. pedunculosum and conducted bioinformatics analysis of the crucial enzyme genes involved in the biosynthetic process using genomic and transcriptomic data. We identified candidate genes for six key enzymes in the biosynthetic pathway. This review reports on the current literature on pharmacological investigations of H. pedunculosum , proposing its potential as an antidiabetic agent. Moreover, we conclude, for the first time, the identification of key enzyme genes potentially involved in the biosynthesis of active compounds in H. pedunculosum. This review provides a scientific foundation for the discovery of novel therapeutic agents from natural sources. [Display omitted] [ABSTRACT FROM AUTHOR]

Coptis teeta Wall., an endangered but valuable medicinal species having various folklore uses in Indian and Chinese Traditional system of medicine. Its distribution is restricted to India, China and Tibet. In India, C. teeta is traditionally used in joint disorders, urinary infections and inflammatory diseases, however the scientific validation is missing. Thus, the present study aims to validate the anti-lithiatic and anti-gout activity of C. teeta rhizome extract (CTME) through in-vitro biological assays. The metabolic fingerprinting of CTME through reverse phase-high performance liquid chromatography-photodiode array (RP-HPLC-PDA) showed the presence of five benzyl-isoquinoline alkaloids, namely berberine (2.59%), coptisine (0.746%) jatrorrhizine (0.133%), palmatine (0.03%) and tetrahydropalmatine (0.003%). The anti-gout potency analysed via in-vitro xanthine oxidase (XOD) inhibition assay, followed by HPTLC (High performance thin layer chromatography) mediated bio-autographic inhibition of XOD signifies that CTME exhibit strong inhibition of XOD (IC 50 : 3.014 μg/ml), insignificantly different (p > 0.05) from allopurinol (IC 50 : 2.47 μg/ml). The XOD bioautographic assay advocates that the efficacy is primarily due to berberine and coptisine alkaloids. The CTME has significant anti-lithiatic activity, and thereby limiting the progression of crystal nidus formation, mediated via inhibition of calcium oxalate crystals nucleation and aggregation. Additionally, the extract also exhibits potential effect on inhibition of oxidative stress associated inflammation, which plays crucial role in alleviating urolithiasis and gouty conditions. Validating the traditional claims of C. teeta will not only confirm its medicinal benefits for targeted pathological conditions but also enhance its industrial demand. [Display omitted] • Coptis teeta has several uses in Indian and Chinese traditional systems of medicine. • Alkaloids content varies from 0.003 to 2.59%, rich source of berberine and coptisine. • Promising invitro antilithiatic and antigout activities validates the traditional usage. • Coptisine, therapeutically at par with berberine but less toxic and may be used as its alternative. [ABSTRACT FROM AUTHOR]

Acute gouty arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia (HUA), is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment. This review briefly summarizes the current potential pharmacological mechanisms of THMs – including active ingredients, extracts, and prescriptions –in the treatment of AGA, and discusses the relevant potential mechanisms and molecular targets in depth. The objective of this study is to offer extensive information and a reference point for the exploration of targeted AGA treatment using THMs. This review obtained scientific publications focused on in vitro and in vivo studies of anti-AGA THMs conducted between 2013 and 2023. The literature was collected from various journals and electronic databases, including PubMed, Elsevier, ScienceDirect, Web of Science, and Google Scholar. The retrieval and analysis of relevant articles were guided by keywords such as "acute gouty arthritis and Chinese herbal medicine," "acute gouty arthritis herbal prescription," "acute gouty arthritis and immune cells," "acute gouty arthritis and inflammation," "acute gouty arthritis and NOD-like receptor thermoprotein domain associated protein 3 (NLRP3)," "acute gouty arthritis and miRNA," and "acute gouty arthritis and oxidative stress." We found that AGA has a large number of therapeutic targets, highlighting the effectiveness the potential of THMs in AGA treatment through in vitro and in vivo studies. THMs and their active ingredients can mitigate AGA symptoms through a variety of therapeutic targets, such as influencing macrophage polarization, neutrophils, T cells, natural killer (NK) cells, and addressing factors like inflammation, NLRP3 inflammasome, signaling pathways, oxidative stress, and miRNA multi-target interactions. The anti-AGA properties of THMs, including their active components and prescriptions, were systematically summarized and categorized based on their respective therapeutic targets. phenolic, flavonoid, terpenoid and alkaloid compounds in THMs are considered the key ingredients to improve AGA. THMs and their active ingredients achieve enhanced efficacy through interactions with multiple targets, of which NLRP3 is a main therapeutic target. Nonetheless, given the intricate composition of traditional Chinese medicine (TCM), additional research is required to unravel the underlying mechanisms and molecular targets through which THMs alleviate AGA. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial. Methods: Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100‐mg increments from 200–400 mg or 300–600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV‐related cause. The latter subgroup included patients who died due to non‐CV causes and those who did not die due to any cause. Results: Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow‐up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient‐years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient‐years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV‐related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of >50%. Conclusion: In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat. [ABSTRACT FROM AUTHOR]

Flare is the dominant feature of gout and occurs because of inflammatory response to monosodium urate crystals; prevention of gout flares should be the major goal of gout care. However, a paradoxical increase in the risk of flare following initiation of urate-lowering therapy presents considerable challenges for proving the expected long-term benefits of flare prevention in clinical trials. Nevertheless, excluding from enumeration flares that occur in the initial post-randomization period (which can last several months to 1 year) can threaten the core benefits of randomization: the characteristics of the remaining participants can differ from those who were randomized, introducing potential bias from confounding (both measured and unmeasured); participants who drop out or die are excluded from the analysis, introducing potential selection bias; and, finally, ignoring initial flares underestimates participants' experience during the trial. This Perspective discusses these issues and recommends measures that will allow for high-level evidence that preserves the randomization principle, to satisfy methodological scrutiny and generate robust evidence-based guidelines for gout care. [ABSTRACT FROM AUTHOR]

Uric acid, which causes gout, is the end product of purine catabolism, synthesized by xanthine oxidase, guanine deaminase, adenine deaminase, purine nucleoside phosphorylase, and 5-nucleotidase II. Garlic contains bioactive compounds that have potential as antigout agents. Garlic fermentation to black garlic changes its components, which may affect its beneficial potential. This study aimed to select types of garlic (Indonesian garlic) and imported garlic, and to predict the interaction between their compounds and five target proteins through an in silico approach and a multivariate analysis, namely partial least squares-discriminant analysis (PLS-DA), to determine their different constituents. The target proteins were collected from open-access databases, and the compounds were identified using mass spectrometry data. The PLS-DA score plot succeeded in classifying the samples into three classes, with each class having a discriminatory compound. Based on the in silico studies, we predicted the best binding score of the five target proteins with seven important compounds: alliin, N-acetyl-S-allyl-L-cysteine, ajoene, pyridoxal, pyridoxamine, 4-guanidinobutyric acid, and D-glucosamine. These were mostly found in black garlic, with no different concentrations in the local and imported samples. Through this approach, we concluded that black garlic is a better candidate for antigout treatments, as several compounds were found to have good binding to the target proteins. [ABSTRACT FROM AUTHOR]

Gout flares, caused by monosodium urate crystals in joints, are debilitating and linked to poor health outcomes. Gout prevalence increases with age, but effective treatment is available even in those with associated renal, cardiovascular and metabolic comorbidities. Treatment includes immediate pain relief with low-dose colchicine, non-steroidal anti-inflammatory drugs, or oral/parenteral corticosteroids; with parenteral corticosteroids useful in older patients. Lifelong urate-lowering therapy and patient education, are typically recommended to reduce the risk of recurring gout flares. [ABSTRACT FROM AUTHOR]

Background/purpose: Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan.Methods: Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed.Results: A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively.Conclusion: The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety. [ABSTRACT FROM AUTHOR]

Objective: To identify predictors of admission following emergency department (ED) attendances for gout flares and to describe barriers to optimal inpatient gout care.Methods: ED attendances and hospital admissions with primary diagnoses of gout were analyzed at 2 UK-based hospitals between January 1, 2017, and December 31, 2020. Demographic and clinical predictors of ED disposition (admission or discharge) and reattendance for gout flares were identified using logistic regression and survival models, respectively. Case note reviews (n = 59), stakeholder meetings, and process mapping were performed to capture detailed information on gout management and to identify strategies to optimize care.Results: Of 1220 emergency attendances for gout flares, 23.5% required hospitalization (median length of stay: 3.6 days). Recurrent attendances for flares occurred in 10.4% of patients during the study period. In multivariate logistic regression models, significant predictors of admission from ED were older age, overnight ED arrival time, higher serum urate (SU), higher C-reactive protein, and higher total white cell count at presentation. Detailed case note reviews showed that only 22.6% of patients with preexisting gout were receiving urate-lowering therapy (ULT) at presentation. Initial diagnostic uncertainty was common, yet rheumatology input and synovial aspirates were rarely obtained. By 6 months postdischarge, 43.6% were receiving ULT; however, few patients had treat-to-target dose optimization, and only 9.1% achieved SU levels ≤ 360 μmol/L.Conclusion: We identified multiple predictors of hospitalization for acute gout. Treat-to-target optimization of ULT following hospitalization remains inadequate and must be improved if admissions are to be prevented. [ABSTRACT FROM AUTHOR]

The article describes the case of a 77-year-old woman with arterial hypertension and a history of stroke and with a three-month history of slowly progressive gait impairment due to muscle weakness and hypotesthesia of the lower limbs. Topics include finding on physical examination, a diagnosis of tophaceous gout, and the need to recognize the clinical signs of gout and acknowledge the potential formation of monosodium urate (MSU) crystals in the spine as a cause of neurological symptoms.

Background: Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.Methods: MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events.Results: NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m2, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m2, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified.Conclusions: Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function.Trial Registration: This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12th November 2019. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout. Methods: We undertook a 2‐year, double‐blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate–lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate–lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points. Results: Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between‐group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health‐related quality of life, and activity limitation) improved in both groups over 2 years, with no between‐group differences. Adverse event and serious adverse event rates were similar between the groups. Conclusion: Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate‐lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to examine the reasons patients give for nonadherence to allopurinol and to examine differences in intentional nonadherence for patients who did and did not achieve serum urate (SU) levels at treatment target.Methods: Sixty-nine men with gout attending rheumatology clinics, all prescribed allopurinol for ≥ 6 months, completed the Intentional Non-Adherence Scale (INAS). Differences in the types of intentional nonadherence were analyzed between those who did and did not achieve SU at treatment target (< 0.36 mmol/L, 6 mg/dL).Results: The most frequently endorsed reasons for not taking their urate-lowering therapies (ULT) were because participants wanted to lead a normal life (23%) or think of themselves as a healthy person again (20%). Patients also reported not taking allopurinol as a way of testing if they really needed it (22%). Participants with SU above target endorsed significantly more INAS items as reasons for not taking their medication, had more medicine-related concerns, and were more likely to give Testing treatment as a reason for nonadherence. Participants who were younger, single, and non-New Zealand European also endorsed more reasons for not taking their allopurinol.Conclusion: The major reasons behind the patient's decision not to take allopurinol relate to the desire to lead a normal life and the strategy of testing the treatment to see if they could reduce the dose without getting symptoms. These results provide some potentially modifiable targets for adherence interventions and some recommendations to clinicians about how to reframe ULT for patients in order to improve adherence. [ABSTRACT FROM AUTHOR]

Increased uric acid levels and inflammatory reactions are the main factors considered responsible for the development of gouty arthritis. Phyllanthus emblica L. (PEL) has several promising pharmacological properties, including anti-inflammation and antioxidation. However, only a few studies have investigated its use for treating acute gouty arthritis (AGA), and the mechanism of action of PEL has not yet been clarified. The aim of this study was to verify the protective effects of PEL against gout and explore its underlying mechanism through network pharmacology and animal experiments. The main active components of the extract from PEL including mucic acid, mucic acid lactone, gallic acid, ethyl hexyl phthalate, and glucose were identified by UPLC-ESI-qTOF-MS. Network pharmacological analysis results revealed 13 active compounds in PEL and 85 related targets for the treatment of gout. The core mechanism of action of PEL is mainly associated with inflammation-related pathways, including the HIF-1, PI3K-Akt, TNF, and NOD-like receptor signaling pathways. Previous studies revealed that the NOD-like receptor signaling pathway, especially the NLRP3 inflammasome, plays an important role in the pathogenesis of AGA; therefore, we mainly investigated the effect of PEL on the NLRP3/ASC/caspase-1 pathway in gout rats. In the animal experiments, PEL was shown to have a satisfactory antigout effect, as it effectively reduced uric acid (UA) and xanthine oxidase (XOD) levels. In terms of inhibiting AGA-associated inflammatory reactions, our results showed that PEL significantly decreased the expression of NLRP3 and caspase-1 in ankle synoviocytes as well as the levels of downstream inflammatory factors, such as TNF-α, IL-10, and IL-1β in serum. Moreover, the results of our study show that PEL reduced MMP13 expression in the ankle synovium. Overall, the results of this study indicate that PEL exerted a therapeutic effect against AGA. Reducing uric acid levels, inhibiting inflammation, and decreasing the expression of MMP13 may be responsible for the therapeutic effect of PEL, which suggests that PEL can be further developed as a drug for the treatment of gout. [ABSTRACT FROM AUTHOR]

Background: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown.Objective: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD.Design: Cohort study.Setting: The Health Improvement Network U.K. primary care database (2000 to 2019).Participants: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.Measurements: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators.Results: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07).Limitation: Residual confounding cannot be ruled out.Conclusion: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD.Primary Funding Source: Project Program of National Clinical Research Center for Geriatric Disorders. [ABSTRACT FROM AUTHOR]