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Aims Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels. Methods and results A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia. Conclusion In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

Objective Several observational studies reported that allopurinol, an effective treatment for gout, was associated with important reductions in cardiovascular events, with calls for large randomized trials, though some results were conflicting. We assessed the extent of time-related biases in these observational studies. Methods We searched the literature for all observational studies reporting on allopurinol and cardiovascular events, focusing on two time-related biases. Time-related confounding bias results from studies using cohorts of patients all exposed to allopurinol, with comparisons based on episodes of allopurinol discontinuation, where confounding factors are not updated over follow-up time. Immortal time bias arises from the exposure misclassification of periods of cohort follow-up during which the outcome under study cannot occur. Results We identified 12 studies, of which eight were affected by time-related confounding bias or immortal time bias, while the remaining four studies avoided these biases. The studies affected by time-related confounding bias resulted in significant reductions in the incidence of cardiovascular events with allopurinol use (pooled hazard ratio 0.88; 95% CI: 0.85-0.92), as did the studies affected by immortal time bias (pooled hazard ratio 0.79; 95% CI: 0.72-0.87). The four studies that avoided these biases resulted in a pooled hazard ratio of 1.07 (95% CI: 0.91-1.25). Conclusions Observational studies reporting significantly reduced incidence of cardiovascular events with allopurinol use were affected by time-related biases. Overall, studies that avoided these biases did not find a protective effect. The ALL-HEART randomised trial will provide important and accurate evidence on the potential effectiveness of allopurinol on cardiovascular outcomes.

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

Gout arthritis commonly affects joint regions by deposition of crystals, promoting functional damage mainly during periods of exacerbation. Cryotherapy is a commonly used resource to contain inflammatory processes, however, its use during a gout crisis is not yet well understood. Therefore, the objective was to evaluate the parameters of Wistar rats submitted to an experimental gout model and treated with dual cryotherapy protocol. Twenty-one male Wistar rats were used, separated into three groups: control group (CG), lesion group (LG), and lesion + cryotherapy group (LCG). Gout model induction was through intra-articular injection, with urate crystal solution, in the right knee and cryoimmersion treatment was performed for 20 minutes at a temperature of 5° ± 2°C. Seven evaluations and two treatment moments were performed, and the following parameters were analyzed: joint edema, grip strength, joint disability, motor function, and leukocyte migration through synovial lavage. In the statistical analysis we used SPSS 20.0 with Generalized Linear Models, with least significant difference posttest, always with 5% significance level. The treatment reduced edema, promoted strength recovery, and was effective in reducing total leukocytes in the synovial fluid. No difference was observed between the injured groups for joint disability and motor function. Cryotherapy promoted edema reduction and increased pelvic limb grip strength in Wistar rats during the acute period.

To evaluate demographic characteristics, care encounters, comorbidities, and clinical differences in Hmong and non-Hmong patients with gout.Using retrospective chart review, all inpatient encounters (Hmong versus non-Hmong) were reviewed from 2014 to 2017. Acute or chronic gout was the primary or secondary diagnosis for the encounter.Hmong gout patients were on average 11 years younger than non-Hmong patients, but after adjustment for age, sex, and type of encounter, they had similar rates of hypertension, diabetes mellitus, and heart disease. Hmong patients had significantly decreased renal function at the time of presentation; the odds ratio of chronic kidney disease for Hmong patients was 2.33 versus 1.48 for non-Hmong patients (P 0.05), the mean creatinine level was 3.3 mg/dl versus 2.0 mg/dl (β = 1.35, P 0.001), and the glomerular filtration rate was 44.8 ml/minute versus 49.3 ml/minute (β = -6.95, P 0.001). Hmong gout patients were more likely to use emergency care versus elective or urgent care, they were less likely to be using medications for the treatment of gout prior to admission (32.3% versus 58.2%), and the length of hospital stay was increased (8.8 versus 5.2 days; P 0.05).Hmong gout patients who had a tertiary care encounter were 11 years younger than non-Hmong patients with similar rates of comorbidities but had worse renal function despite the age differences. They were more likely to use emergency services, to be insured through Medicaid, and not to use preventive medications for gout prior to their encounter. Intensive efforts are needed in the Hmong population for culturally appropriate preventive care management of gout along with diabetes mellitus, hypertension, heart disease, and kidney disease.

Contains fulltext : 249973.pdf (Publisher’s version ) (Closed access) Over the last decade, evidence has demonstrated that long-term, low-dose colchicine (0.5 mg daily) is effective for preventing gout flare and cardiovascular (CV) events in a wide range of patients. Given the potentially expanding use of colchicine in CV disease, we here review and update the biologic effects and safety of colchicine based on recent data gathered from bench and pharmacodynamic studies, clinical reports, controlled clinical trials, and meta-analyses, integrated with important studies over the last 50 years, to offer a consensus perspective by experts from multiple specialties familiar with colchicine's long-term use. We conclude that the clinical benefits of colchicine in gout and CV disease achieved at low dose do not sustain serum levels above the upper limit of safety when used in patients without advanced renal or liver disease or when used concomitantly with most medications. Further, data accrued over the last 50 years strongly suggest that the biologic effects of long-term colchicine do not increase the risk of cancer, sepsis, cytopenia, or myotoxicity.

Background/Purpose Disordered osteoclast activity has been implicated in the pathogenesis of gouty bone erosion. We sought to determine if the addition of denosumab (a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand - RANKL) to intensive urate-lowering therapy (ULT) improves gouty bone erosion. Methods Open-label, parallel-group pilot randomized controlled trial in which 20 participants with gout with at least one confirmed conventional radiographic foot bone erosion were assigned in a 1:1 allocation to receive denosumab (60 mg subcutaneous every 6 months) added to intensive ULT (serum urate ≤5 mg/dL or 300 µmol/L at the time of randomization and continued for the duration of the study), or intensive ULT alone. The primary outcome was the change in the bilateral foot and ankle computed tomography (CT) bone erosion score from baseline to 12 months, assessed by an experienced musculoskeletal radiologist blinded to study assignment. Secondary outcomes included change in serum C-terminal telopeptide (CTX), and patient reported outcomes of pain and function. Results Although serum CTX declined markedly in the denosumab/ULT group compared with the ULT alone group, there was no interval change in CT erosion score in either the denosumab/ULT or ULT alone group after one year of follow-up. Other secondary outcomes did not differ between groups. There were two severe adverse events: One patient developed atrial fibrillation (on denosumab/ULT) and another atrial flutter (on ULT alone). Conclusions In this pilot study, denosumab did not offer additional benefit to intensive urate lowering therapy for gouty bone erosion.

Introduction Gout is the most common inflammatory arthritis, but was not considered in most COVID-19 and rheumatic diseases reports. Our aim was to describe changes in clinical data, treatment, function and quality of life for gout patients during COVID-19 pandemic. Methods Prospective, descriptive and analytical study of 101 consecutive gout (ACR/EULAR 2015) patients from our clinic evaluated during pandemic by phone call (n=52) or phone call + face-to-face (n=68) that accepted to participate. Variables are demographics, clinical and treatment data, HAQ, EQ5D questionnaires and COVID-19-related data. Patients were divided in two groups: flare (n=36) or intercritical gout (n=65) also; available pre-pandemic data was obtained from 71 patients. Statistical analyses are X2, paired t-test and Wilcoxon test. Results Included gout patients were males (95.8%), mean (SD) age 54.7 (10.7) years and disease duration 16.4 (9.8) years; 90% received allopurinol, 50% colchicine as prophylaxis and 25% suspended ≥ 1 medication. Comparison of pre-pandemic vs pandemic data showed > flares (4.4% vs 36%, p=0.01), more flares in the last 6 months: 0.31 (0.75) vs 1.71 (3.1), (p=0.004 and > urate levels: 5.6 (1.7)vs 6.7 (2.2) mg/dL, p=0.016. Unexpectedly, function and quality-of-life scores improved: HAQ score 0.65 (2.16) vs 0.12 (0.17), p= 0.001. Seven patients were COVID-19-confirmed cases; they had significantly more flares, higher urate levels and lower allopurinol doses and two died. Conclusions In gout patients, flares were 9 times more frequent during pandemic also, they had increased urate levels but led to an unexpected improvement in HAQ and functionality scores. Resilience and lifestyle changes in gout during COVID-19 pandemic require further studies. Key Points • COVID-19 pandemic is associated with 4 times more flares in gout patients.• Increased flares were also seen in previously well-controlled gout patients.• Increased serum urate levels were also found in gout patients during pandemic.• In our gout clinic, 8/101 patients were diagnosed as COVID-19+, and two of them died.

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1s/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions—within 30 days and, ideally, within 3 days—or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established.

Previous research has investigated whether hyperuricemia serves as an independent risk factor for cardiovascular and renal diseases. Hyperuricemia is defined as an abnormally high level of uric acid (UA; i.e., serum urate level > 6.8 mg/dL). Hyperuricemia has been considered a complication of chronic kidney disease (CKD). However, it seems to play a pathogenic role in the progression of renal diseases. There has been increasing focus on the link between hyperuricemia and CKD. The results of randomized controlled trials have implied independent associations between hyperuricemia and the progression of cardiovascular and renal morbidities. These associations may be mediated by renin-angiotensin system activation, nitric oxide synthase inhibition, and macrovascular/microvascular disease development. There remains controversy regarding the use of serum UA level as an indirect index of renal vascular disease. This literature review focuses on the role of asymptomatic hyperuricemia in the progression of CKD, as well as the association between hyperuricemia and cardiovascular disease. It also provides a general overview of the physiological metabolism of UA.

BackgroundUrate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs).MethodsIn a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence.ResultsThe 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n= 152) or stress reduction video (n= 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p> 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p= 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p= 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p= 0.003), and 6 months, 29.5 vs. 34.5 (p= 0.03), respectively.ConclusionsA culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout.Trial registrationRegistered atClinicalTrials.govNCT02741700

WHAT IS KNOWN AND OBJECTIVE Reduction in skeletal muscle mass is the most important component in diagnosing sarcopenia. Ageing and chronic heart failure due to cardiovascular diseases (CVDs) accelerate the reduction of skeletal muscles. However, there are no currently available drugs that are effective for sarcopenia. The purpose of this study was to explore the association between prescribed medications and skeletal muscle mass in patients with CVD. METHODS This was a single-centre, retrospective, cross-sectional study. The subjects were 636 inpatients with CVD who took prescribed medicines for at least 4 weeks at the time of admission. Skeletal muscle volume was assessed using a bioelectrical impedance assay. RESULTS AND DISCUSSION Single regression analysis showed that 10 and 3 medications were positively and negatively associated with skeletal muscle index (SMI), respectively. Stepwise multivariate regression analysis revealed that angiotensin II receptor blocker (ARB)/statin combination, dipeptidyl peptidase-4 inhibitor, and antihyperuricemic agents were positively associated with SMI while diuretics and antiarrhythmic agents were negatively associated with SMI. After adjustment using propensity score matching, the SMI was found to be significantly higher in ARB/statin combination users than in non-users. WHAT IS NEW AND CONCLUSION Combination use of ARB/statin was associated with a higher SMI in patients with CVD. A future randomised, controlled trial is warranted to determine whether the ARB/statin combination will increase the SMI and prevent sarcopenia in patients with CVD.

AIM: Despite the effectiveness and availability of urate-lowering therapies (ULT), we continue to see a number of advanced cases of tophaceous gout in the Pacific Islander and Maori population in Western Sydney. Although the high prevalence and increased severity of gout in this cohort has been well documented, there has been little qualitative research undertaken in Australia into the lived experience of this group of people. It is this gap in the research that our study aimed to address. METHODS: Participants were recruited from the rheumatology clinics at Westmead and Blacktown Hospitals. Those eligible to participate were Pacific Islander and Maori patients with tophaceous gout currently living in the Western Sydney Local Health District (WSLHD). Data collection took the form of 10 semi-structured interviews, which were subsequently transcribed verbatim. A thematic analysis of the data was then performed. RESULTS: Thematic analysis identified 6 key themes: lack of understanding of the disease and its potential effects; missed opportunities for intervention and disjointed care; chronic reliance upon corticosteroids; trivialization of gout as a nuisance illness; the substantial financial impact of chronic illness; and the all-consuming nature of severe gout. CONCLUSION: The human cost of severe tophaceous gout in this cohort is immense. All 10 participants exemplified the disease's devastating social effects. We propose 4 key recommendations: improved education regarding diagnosis and management; immediate prescription of ULT at first presentation; a lower threshold for out-of-hospital rheumatologist referral; and improved follow-up through a nurse- and pharmacist-led collaborative gout management program.

Objectives Hyperuricaemia is recognized as an independent risk marker for cardiovascular and renal diseases. However, uric acid is a powerful free-radical scavenger, and the optimal level of serum uric acid (SUA) determining outcomes is unknown. This study explored whether interventional treatments for excessive SUA reduction were harmful and what constituted the optimal lowering of SUA levels for the prevention of events in patients with asymptomatic hyperuricaemia. Methods This was a post hoc analysis of a randomized trial (Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy [FREED]) in which 1070 older patients with asymptomatic hyperuricaemia were enrolled and allocated to febuxostat (n = 537) or non-febuxostat treatment group (n = 533). We assessed the relationship between the endpoint (withdrawal or study completion) SUA levels and clinical outcomes. Primary endpoint was defined as a composite of all-cause mortality, cerebral and cardiorenovascular events. Results In the febuxostat group, patients achieving SUA levels ≤4 mg/dl (hazard ratio: 2.01 [95% CI: 1.05, 3.87]), >4 to ≤5 mg/dl (2.12 [1.07, 4.20], >6 to ≤7 mg/dl (2.42 [1.05, 5.60]), and >7 mg/dl (4.73 [2.13, 10.5]) had significantly higher risks for a primary composite event than those achieving SUA levels >5 to ≤6 mg/dl (P = 0.003 [log-rank test]). This J-shaped relationship applied to patients with renal impairment (P = 0.007 [Gray’s test]) and was not significant in the non-febuxostat treatment group (P = 0.212 [log-rank test]). Conclusion Optimal SUA level by febuxostat treatment is 5–6 mg/dl for reducing all-cause mortality, cerebral, cardiovascular and renal events. Excessive SUA reduction may be harmful in older hyperuricaemic populations. Trial Registration ClinicalTrial.gov, https://clinicaltrials.gov, NCT01984749

Background The prevalence of renal calculi in patients with gout is high. Alkalized urine has been recommended by the 2020 European Association of Urology (EAU) guidelines to promote calculus dissolution. However, randomized controlled trials are lacking. Methods In the protocol of this randomized, placebo-controlled, double-blinded trial, patients with gout combined with renal calculi are randomized (1:1) to the placebo and sodium bicarbonate groups. The intervention would be performed for 24 weeks, the 1–12 weeks are double-blinded, and the 13–24 weeks are open-labeled. Sodium bicarbonate (1 g tid) will be performed for 24 weeks in the sodium bicarbonate group. The placebo will be performed for 12 weeks and not be performed from 13 weeks to 24 weeks in the placebo group. All subjects will be administered febuxostat (40 mg/day) for 24 weeks and receive concomitant anti-inflammatory prophylaxis therapy for 12 weeks. The primary outcome is the proportion of patients whose renal calculus volume will be reduced after 12 weeks of treatment. The secondary outcomes include the volume changes of renal calculi, uric acid changes, the proportion of patients with serum uric acid (sUA) levels < 360 μmol/L, the changes in estimated glomerular filtration rate (eGFR), the pH value of urine, and the incidence of adverse events after treatment for 12 and 24 weeks. Discussion This study will evaluate the efficacy and safety of sodium bicarbonate-alkalized urine on renal calculi in patients with gout. Trial registration ClinicalTrials.gov ChiCTR2100045183. Registered on April 7, 2021, with ChiCTR.

Objective To evaluate the impact of incorporating treatment guidance into reporting of urate test results. Methods Urate targets for clinically confirmed gout were added to urate results above 0.36 mmol/l requested after September 2014 within NHS Lothian. Scotland-wide data on urate-lowering therapy prescriptions and hospital admissions with gout were analysed between 2009 and 2020. Local data on urate tests were analysed between 2014 and 2015. Results Admissions with a primary diagnosis of gout in Lothian reduced modestly following the intervention from 111/year in 2010–2014 to 104/year in 2015–2019, a non-significant difference (P = 0.32). In contrast there was a significant increase in admissions to remaining NHS Scotland health boards (556/year vs 606/year, P Conclusion Incorporation of clinical guideline advice into routine reporting of urate results was associated with reduced rates of admission with gout in NHS Lothian, in comparison with other Scottish health boards.

The history of colchicine dates to ancient Egyptians when it was used for alleviation of swelling and pain. Although its popularity varied throughout the years, colchicine has been a mainstay for the treatment of several diseases, mainly rheumatic and cardiac ones. The mechanism of action of the drug involves several intracellular and extracellular targets, although interaction with tubulin is the most described. Based on several clinical trials and meta-analyses, colchicine is safely recommended as a monotherapy or as an add-on for the treatment and prevention of recurrent pericarditis, post-pericardiotomy syndrome, gout, pseudogout, familial Mediterranean fever (FMF), and Behçet’s disease (BD). Notably, drug safety has been noted during pregnancy and lactation. Besides its major indications, colchicine has shown efficacy and safety in the treatment of various conditions. Because the indications for using colchicine in the prevention of certain conditions such as acute coronary syndrome, stroke, and hepatic cirrhosis and treatment of others such as pneumonia and psoriasis are still debatable, further research works are needed.

Background: Colchicine reduces risk of cardiovascular events in patients post–myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). Objectives: This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. Methods: The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. Results: In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). Conclusions: The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684)

Gout and chronic kidney disease (CKD) frequently coexist, but quality evidence to guide gout management in people with CKD is lacking. Use of urate-lowering therapy (ULT) in the context of advanced CKD varies greatly, and professional bodies have issued conflicting recommendations regarding the treatment of gout in people with concomitant CKD. As a result, confusion exists among medical professionals about the appropriate management of people with gout and CKD. This Consensus Statement from the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) discusses the evidence and/or lack thereof for the management of gout in people with CKD and identifies key areas for research to address the challenges faced in the management of gout and CKD. These discussions, which address areas for research both in general as well as related to specific medications used to treat gout flares or as ULT, are supported by separately published G-CAN systematic literature reviews. This Consensus Statement is not intended as a guideline for the management of gout in CKD; rather, it analyses the available literature on the safety and efficacy of drugs used in gout management to identify important gaps in knowledge and associated areas for research., In this Consensus Statement, members of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) highlight gaps in knowledge about the management of gout in people with chronic kidney disease, and identify important areas for future research to address challenges in the treatment of this patient population.

Cachexic condition due to malignant tumors has been a challenging problem. The aim of this study is to analyze effects of febuxostat on both in vitro and in vivo models of the wasting of skeletal muscles, due to LM8 osteosarcoma cells. C2C12 myotubes were incubated in the conditioned medium of LM8. Febuxostat was added at a concentration of 3 µM and 30 µM, and ROS, diameter of myotubes, and expression of atrogin-1 were analyzed. Furthermore, an in vivo study was performed by subcutaneous injection of LM8 on C3H mice. Febuxostat was administered in the drinking water at 5 µg/ml, and 25 µg/ml. In addition, tumor-bearing mice without febuxostat (group TB) and control mice (group C) were established. At 4 weeks, body weight, wet weights of the gastrocnemius muscles, XO activity, 8-OHdG, and expression of TNF-α and IL-6 were evaluated. ROS generation, atrophy of myotubes, and upregulation of atrogin-1 were clearly observed in C2C12 myotubes following incubation in the conditioned medium. These pathological conditions were significantly inhibited by febuxostat administration. Furthermore, mice in group TB showed significant loss of body weight and muscle weight in which XO activity, 8-OHdG, and expression of IL-6 were significantly increased compared to those in group C. Febuxostat administration not only significantly improved the body weight and muscleweight, but also reduced markers of oxidative stress and pro-inflammatory cytokines. Febuxostat did not show anti-tumor effects. Febuxostat, which is clinically used for treatment of hyperuricemia, is effective against the wasting of the skeletal muscles induced by LM8 osteosarcoma cells.

OBJECTIVE Urate-lowering therapy (predominantly allopurinol) is highly effective as a treatment for gout, but its wider long-term effects remain unclear. This systematic review and meta-analysis aimed to ascertain the association between mortality and the use of allopurinol in patients with gout. METHOD Medline, Embase, CINAHL, and the Cochrane Library were searched from inception to August 2018. Articles eligible for inclusion used a cohort design and examined cardiovascular or all-cause mortality in patients diagnosed with gout and prescribed allopurinol. Information on study characteristics, design, sample size, and mortality risk estimates were extracted. Article quality was assessed using the Newcastle-Ottawa Scale. Included articles were described in a narrative synthesis and, where possible, risk estimate data were pooled. RESULTS Four articles reported a hazard ratio (HR) risk estimate for all-cause mortality in patients with gout using allopurinol, and 2 of these also reported cardiovascular mortality. Two articles found allopurinol to be protective in patients with gout, 1 found no statistically significant association, and 1 found no statistically significant effect of escalation of allopurinol dosage on all-cause or cardiovascular-related mortality. Data pooling was possible for all-cause mortality and found no association between allopurinol use in patients with gout and all-cause mortality compared to patients with gout not using allopurinol (adjusted HR 0.80 [95% confidence interval 0.60-1.05]). CONCLUSION There was no significant association between all-cause mortality and allopurinol use in people with gout. However, the number of included studies was small, suggesting that further studies are needed.

ObjectiveTo assess health- and patient-centered outcomes in gout across Europe, and explore patient-, care-, and country-level characteristics associated with these outcomes.MethodsPatients with self-reported physician-diagnosed gout from 14 European countries completed an online survey. Multivariable mixed-effect logistic and linear regressions were computed for health outcomes (gout flare recurrence) and patient-centered outcomes (patient satisfaction with current medication, and unaddressed goals), accounting for clustering within countries. The role of patient-, care-, and country-level factors was explored.ResultsParticipants included 1029 patients, predominantly diagnosed by a general practitioner (GP). One or more gout flares were reported by 70% of patients and ≥ 3 flares by 32%. Gout patients reported 1.1 ± 1.2 unaddressed goals, and 80% were satisfied with current medication. Patients with ≥ 3 and ≥ 1 flares were less likely to be treated with urate-lowering therapy (ULT) (OR 0.52, 95% CI 0.39–0.70 and OR 0.38, 95% CI 0.28–0.53, respectively), but more likely to have regular physician visits (OR 2.40, 95% CI 1.79–3.22 and OR 1.77, 95% CI 1.30–2.41). Three or more gout flares were also associated with lower satisfaction (OR 0.39, 95% CI 0.28–0.56) and more unaddressed goals (β 0.36, 95% CI 0.19–0.53). Notwithstanding, the predicted probability of being satisfied was still between 57% and 75% among patients with ≥ 3 flares but who were not receiving ULT. Finally, patients from wealthier and Northern European countries more frequently had ≥ 3 gout flares.ConclusionAcross Europe, many patients with gout remain untreated despite frequent reported flares. Remarkably, a substantial proportion of them were still satisfied with gout management. A better understanding of patients’ satisfaction and its role in physicians’ gout management decisions is warranted to improve quality of care and gout outcomes across Europe.

This prospective study was aimed at observing the changes in three ultrasound (US) outcome domains (urate deposition, joint inflammation and bone erosion) in gout patients within the 1 y on urate-lowering therapy. The elementary lesions, including tophus, double-contour (DC) sign, aggregates, synovitis and bone erosion of the bilateral knee, ankle and first metatarsophalangeal joints, were evaluated repeatedly by US before and after 3, 6 and 12 mo of treatment, and the effective rates of clearance of tophus, DC sign and aggregates in different time groups were compared. A Global OMERACT–EULAR Synovitis Score (GLOESS) was calculated for these three paired joints to observe the inflammation. Bone erosion was also scored. The correlation between serum uric acid levels and tophus size changes was analyzed. Our results indicated that the decrease in serum uric acid levels was not completely parallel to the decrease in tophus size. For tophus, there was no significant difference in the clearance rate between different time groups (χ2 = 1.76, p = 0.392), while for DC sign and aggregates, there were significant differences (χ2 = 21.48, p

BACKGROUND The objective of this meta-analysis of randomised controlled clinical trials (RCT) was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. AIMS Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production. Recent studies suggested the renoprotective effect of febuxostat among hyperuricaemia patients. The aim of this study was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. METHODS We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify RCT that examined the effects of febuxostat in adult patients with hyperuricaemia on serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria, blood pressure parameters, major cardiovascular events, diarrhoea, joint pain, stroke and arrhythmia. RESULTS Nine RCT with 2141 participants were included in this meta-analysis. Compared to placebo, the febuxostat group showed a higher eGFR at 6 months with a weighted mean difference (WMD) of 2.86 mL/min/1.73 m2 (P

Introduction Gout is an inflammatory disease triggered by deposition of urate crystals secondary to longstanding hyperuricemia, and its management implies both the treatment of flares and management of hyperuricemia. Dotinurad is a selective urate reabsorption inhibitor (SURI), potently inhibits urate transporter 1 in the apical surface of renal proximal tubular cells, and has been approved for the treatment of gout and hyperuricemia in Japan. Areas covered This overview of dotinurad covers nonclinical and clinical pharmacology studies in special populations and its efficacy and safety in Japanese hyperuricemic patients with and without gout. Expert opinion Dotinurad, as an SURI, is expected to inhibit urate reabsorption more effectively than conventional urate-lowering agents. It is noninferior to benzbromarone or febuxostat in reducing serum urate levels in hyperuricemic patients with or without gout. Its efficacy is not attenuated in patients with mild to moderate renal impairment or with hepatic impairment. At a maintenance dose of 2 or 4 mg once daily, most patients achieved the target serum urate level of ≤6 mg/dL in a long-term study. No findings that raised safety concerns, including liver injury, were identified. Dotinurad is expected to be a new therapeutic option in hyperuricemic patients with and without gout.

Gout flare prophylaxis and therapy use in people with underlying chronic kidney disease (CKD) is challenging, given limited treatment options and risk of worsening renal function with inappropriate treatment dosing. This literature review aimed to describe the current literature on the efficacy and safety of gout flare prophylaxis and therapy use in people with CKD stages 3–5. A literature search via PubMed, the Cochrane Library, and EMBASE was performed from 1 January 1959 to 31 January 2018. Inclusion criteria were studies with people with gout and renal impairment (i.e. estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) 2), and with exposure to colchicine, interleukin-1 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids. All study designs were included. A total of 33 studies with efficacy and/or safety analysis stratified by renal function were reviewed—colchicine (n = 20), anakinra (n = 7), canakinumab (n = 1), NSAIDs (n = 3), and glucocorticoids (n = 2). A total of 58 studies reported these primary outcomes without renal function stratification—colchicine (n = 29), anakinra (n = 10), canakinumab (n = 6), rilonacept (n = 2), NSAIDs (n = 1), and glucocorticoids (n = 10). Most clinical trials excluded study participants with severe CKD (i.e. eGFR or CrCl of 2). Information on the efficacy and safety outcomes of gout flare prophylaxis and therapy use stratified by renal function is lacking. Clinical trial results cannot be extrapolated for those with advanced CKD. Where possible, current and future gout flare studies should include patients with CKD and with study outcomes reported based on renal function and using standardised gout flare definition.

Rationale & Objective Hyperuricemia has been implicated in the development and progression of chronic kidney disease. Verinurad is a novel, potent, specific urate reabsorption inhibitor. We evaluated the effects on albuminuria of intensive urate-lowering therapy with verinurad combined with the xanthine oxidase inhibitor febuxostat in patients with hyperuricemia and type 2 diabetes mellitus (T2DM). Study Design Phase 2, multicenter, prospective, randomized, double-blind, parallel-group, placebo-controlled trial. Setting & Participants Patients 18 years or older with hyperuricemia, albuminuria, and T2DM. Intervention Patients randomly assigned 1:1 to verinurad (9mg) plus febuxostat (80mg) or matched placebo once daily for 24 weeks. Outcomes The primary end point was change in urinary albumin-creatinine ratio (UACR) from baseline after 12 weeks' treatment. Secondary end points included safety and tolerability and effect on glomerular filtration. Results 60 patients were enrolled (n=32, verinurad and febuxostat; n=28, placebo). UACRs after treatment with verinurad plus febuxostat were lower than after placebo at 1, 12, and 24 weeks: −38.6% (90% CI, −60.9% to−3.6%), −39.4% (90% CI, −61.8% to−3.8%), and−49.3% (90% CI, −68.2% to−19.0%), respectively. Serum urate levels after treatment with verinurad plus febuxostat were 59.6% and 63.7% lower than after placebo at 12 and 24 weeks, respectively. No clinically meaningful changes were observed in estimated glomerular filtration rate or serum creatinine or serum cystatin C concentrations. Verinurad plus febuxostat was well tolerated. Limitations Sample size and study duration were insufficient to evaluate definitive effects of verinurad plus febuxostat on UACR and glomerular filtration. Generalizability was limited by exclusion of patients with stages 4 and 5 chronic kidney disease. Conclusions Verinurad plus febuxostat reduced albuminuria and lowered serum urate concentrations in patients with T2DM, albuminuria, and hyperuricemia. Definitive assessment of their combined impact on preservation of kidney function awaits larger clinical studies. Funding This study was supported by AstraZeneca. Trial Registration Registered at ClinicalTrials.gov with study number NCT03118739.

Objectives: Chronic kidney disease (CKD) has emerged as a global health concern. Many studies have identified an association between hyperuricemia and CKD, and some studies have revealed that urate-lowering therapy (ULT) can attenuate CKD progression. However, only a few studies have explored the role of ULT in the prevention of new onset CKD. Methods: To compare the risk of incident CKD between users and nonusers of ULT in patients with gout, we conducted a 13-year population-based retrospective cohort study. Overall incidence of CKD was compared between 7126 ULT users and 7126 matched ULT nonusers. Results: The CKD incidence rate for both the users and nonusers of ULT was 1.7 per 100 person-years, after adjusting for sex, age, region of residence, comorbidities, and medications used. No significant difference in CKD risk (adjusted hazard ratio [aHR]: 0.97; 95% confidence interval [CI]: 0.88-1.07) was noted between the ULT users and nonusers. In the subgroup of patients with diabetes mellitus (DM) and without hypertension (HT), ULT tended to be associated with lower risk of incident CKD (aHR: 0.52; 0.95% CI: 0.28-0.97). Compared with the risk of new onset CKD in patients receiving xanthine oxidase inhibitors, those receiving uricosuric agents seemed to have a lower risk of developing CKD (aHR: 0.81, 95% CI: 0.67-0.99). Conclusion: This population-based cohort study indicated that ULT is not associated with lower risk of CKD development. However, in the subgroup of patients with DM and without HT, ULT is associated with significantly lower risk of incident CKD.

Objective The objective of this study was to compare the prophylactic effect of regular-dose (RD, 1.2 mg/day) vs low-dose (LD, 0.6 mg/day) colchicine on gout flare when initiating urate-lowering therapy. Methods In this retrospective cohort study, we included gout patients who were initiated on either allopurinol or febuxostat, in combination with colchicine therapy and followed them up for 3 months. We analysed the rates of gout flare and adverse events according to the dose of colchicine. We performed the inverse probability of treatment weighting (IPTW) and weighted logistic regression analysis to assess the treatment effect. Analysis of gout flares and adverse events was performed on an intention-to-treat (ITT) and per-protocol (PP) basis. Results Of the total of 419 patients with gout, 177 patients (42.2%) received LD colchicine, whereas 242 patients (57.8%) received RD colchicine. Lower BMI and estimated glomerular filtration rate, and higher incidence of cardiovascular disease were seen in the LD group than in the RD group. In IPTW-adjusted analysis, events of gout flare were not significantly different between the LD and RD groups [ITT: 14.3% vs 11.3%; odds ratio (OR): 1.309, 95% CI: 0.668, 2.566, P = 0.432; PP: 15.3% vs 10.0%; OR: 1.623, 95% CI: 0.765, 3.443, P = 0.207]. However, LD colchicine was associated with a lower rate of adverse events than RD colchicine [ITT: 8.2% vs 17.9%; OR: 0.410, 95% CI: 0.217, 0.777; P Conclusion Our data suggest that LD colchicine can adequately prevent gout flare with fewer adverse events compared with RD colchicine.

Gout is the most common inflammatory arthritis in the United States. Gouty arthritis is associated with significant morbidity and mortality and is the result of chronic hyperuricemia. Gout is effectively managed and potentially cured by decreasing the overall urate burden with serum urate-lowering therapy. When serum urate is maintained at less than 6.0 mg/dL, urate deposition is resolved, and gout can be cured. Unfortunately, because of less than optimal physician monitoring and dose escalation, many patients do not achieve these urate levels.

Refereed/Peer-reviewed Background: Colchicine may offer relief in osteoarthritis. This has never been investigated for hand osteoarthritis. Objectives: To investigate the effect of 1 mg daily colchicine vs placebo on hand pain and function over 12 weeks in older adults with hand osteoarthritis. Methods: Community-dwelling adults with diagnosed osteoarthritis of the hand aged 40–80 years were randomised to receive colchicine (0.5 mg twice daily) or matching placebo. Primary outcome measure was VAS hand pain score (0–100 mm). Secondary outcome measures included tender and swollen joint count, grip strength, C-reactive protein, and Michigan Hand Questionnaire total, function and pain scores. In an exploratory assessment, we compared synovial grade and power Doppler. All outcome measures were obtained at baseline and week 12. Stata v16 was used to perform constrained longitudinal data analysis models. Results: 64 adults (54 females, 10 males) aged 48–79 years of age were enrolled. 59 participants completed the study (N = 28 colchicine, N = 31 placebo) (withdrawal rate 8%). Adverse reactions to the study medication occurred in nine patients. VAS score was not significantly different at baseline (61 ± 17 mm in the colchicine, 64 ± 17 mm in the placebo group). Between-group difference for VAS score at week 12 was 7.6 mm (95% CI -3.5-18.7, p-value 0.18). There were no significant differences between groups for any secondary outcomes at baseline or week 12. Conclusions: 1 mg colchicine daily for 12 weeks was not effective for reducing pain, tender and swollen joint count or increasing grip strength in symptomatic hand osteoarthritis. Our results do not support the use of colchicine in hand osteoarthritis.

Serum uric acid (UA) is taken up by endothelial cells and reduces the level of nitric oxide (NO) by inhibiting its production and accelerating its degradation. Cytosolic and plasma xanthine oxidase (XO) generates superoxide and also decreases the NO level. Thus, hyperuricemia is associated with impaired endothelial function. Hyperuricemia is often associated with vascular diseases such as chronic kidney disease (CKD) and cardiovascular disease (CVD). It has long been debated whether hyperuricemia is causally related to the development of these diseases. The 2020 American College of Rheumatology Guideline for the Management of Gout (ACR2020) does not recommend pharmacological treatment of hyperuricemia in patients with CKD/CVD. In contrast, the Japanese Guideline on Management of Hyperuricemia and Gout (JGMHG), 3rdedition, recommends pharmacological treatment of hyperuricemia in patients with CKD. In a FREED study on Japanese hyperuricemic patients with CVD, an XO inhibitor, febuxostat, improved the primary composite endpoint of cerebro-cardio-renovascular events, providing a rationale for the use of urate-lowering agents (ULAs). Since a CARES study on American gout patients with CVD treated with febuxostat revealed increased mortality, ACR2020 recommends switching to different ULAs. However, there was no difference in the mortality of Japanese patients between the febuxostat-treated group and the placebo or allopurinol-treated groups in either the FEATHER or FREED studies.

Objective Our objective was to determine whether initiation of febuxostat during an acute gout flare prolongs the current episode. Methods In this randomized, placebo-controlled, single-blinded, multicentre trial, patients with acute gout flares within 72 h were randomized (1:1) to the placebo and febuxostat (40 mg/day) groups. All patients were administered diclofenac (150 mg/day) for 7 days and then open-labelled on the eighth day. Febuxostat 40 mg daily and diclofenac 75 mg daily were administered from day 8 through 28 for the remission period. The dose of diclofenac was 150 mg/day before remission in both arms, and the original protocol was maintained until remission. The primary outcome was ‘days to resolution’. Results We randomized 140 patients, 70 into each arm. The mean days to resolution was 5.98 days [median 7.00, interquartile range (IQR) 2.45 days] for the placebo and 6.50 days (median 7.00, IQR 3.67 days) for the febuxostat group (P = 0.578). The rate of resolution within 7 days was 84.38% for the placebo group and 76.92% for the febuxostat group (P = 0.284). There were no statistically significant differences in joint pain, swelling, tenderness and erythema scores at days 1, 3, 5 and 7. The mean serum uric acid levels were 507.54 and 362.62 μmol/l for the placebo and febuxostat group, respectively, on day 7 (P = 0.000). The rate of recurrent gout flares was 10.00% for the placebo group and 6.56% for the febuxostat group from day 8 through 28 (P = 0.492). Conclusion Initiation of febuxostat administration during an acute gout flare did not prolong the duration of acute flares. Trial registration Chinese Clinical Trial Registry, http://www.chictr.org.cn/, ChiCTR1800015962

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open‐label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40–160 mg/day or febuxostat 10–60 mg/day, titrated to maintain serum uric acid, This multicenter, randomised, open‐label study compared the effects of two xanthine oxidoreductase inhibitors, topiroxostat and feboxostat, on arterial stiffness, uric acid levels and blood pressure (BP) in hypertensive patients with hyperuricemia. Neither topiroxostat nor feboxostat had any significant effects on arterial stiffness (measured using the cardio‐ankle vascular index) over 24 weeks' treatment; but both agents significantly reduced serum uric acid levels and morning home systolic BP compared with baseline.

Introduction There is scant data on the role of hyperuricaemia, gout and allopurinol treatment in chronic kidney disease (CKD). Therefore, our aim is to investigate the possible associations between hyperuricaemia, gout, prescription of allopurinol and renal outcomes in patients with CKD. Methods The retrospective cohort study involved 1123 Royal Brisbane and Women’s Hospital (RBWH) patients, enrolled in the CKD.QLD registry from May 2011 to August 2017. Patients were divided into two uric acid categories, with uric acid ≤ 0.36 mmol/L and > 0.36 mmol/L. Association of delta estimated glomerular filtration rate (eGFR) with gout, allopurinol treatment and hyperuricaemia were analysed. Results Patients with an entry urate > 0.36 mmol/L were older, had higher body mass index (BMI) and worse baseline kidney function. Proportion of patients with gout, hyperuricaemia and allopurinol treatment increased with advanced CKD stages. Age-adjusted analysis revealed a significant association between serum urate level and delta eGFR, with no significant association between gout, treatment with allopurinol and delta eGFR. Furthermore, neither gout nor the prescription of allopurinol had a significant effect on the time to renal death (composite end point of kidney replacement therapy or death). Conclusion Hyperuricaemia seemed to be independently associated with faster CKD progression or renal death. This was not observed with gout or prescription of allopurinol. Furthermore, allopurinol was not associated with decreased incidence of cardiovascular events. These data suggest that hyperuricaemia is likely the effect and not the cause of CKD or CKD progression. Graphic abstract

Adenine phosphoribosyltransferase (APRT) deficiency is a rare disorder caused by an autosomal recessive genetic disease leading to the deposition of 2,8-dihydroxyadenine (2,8-DHA) in the kidney. The disease remains under-recognized, oftentimes diagnosed in late stages of renal insufficiency or a failed kidney allograft with biopsy-proven disease recurrence. Here, we present the case of a 59-year-old middle eastern male patient diagnosed with 2,8-DHA nephropathy after a very unusual presentation, and we show how the initiation of an appropriate therapy slowed down his evolution toward kidney replacement therapies. His disease was found to be secondary to a specific APRT gene variant c.188G>A p (Gly63Asp) also described in 4 other patients, all from middle eastern origins.

KEY POINTS A 66-year-old man presented to the emergency department with a 2-week history of progressive weakness and lethargy. Three months before presentation, he had been started on azathioprine therapy for immunoglobulin (Ig) G4-related biliary disease. Comorbidities included hypertension

We report the case of a 77-year-old man with Parkinson's disease (PD) who experimented for the first time gout crisis after the initiation of levodopa. Levodopa was withdrawn, and colchicine and allopurinol were initiated to treat the gout crisis. Because of PD progression, levodopa was reintroduced, and the patient presented relapse of gout flare. To further explore the association between gout and levodopa, we extracted and synthetized all Individual Case Safety Reports of gout associated with levodopa in the World Health Organization pharmacovigilance database, VigiBase® , up to April 2021. 43 cases of gout were reported in VigiBase® with drugs from N04BA ATC class. Levodopa was suspected in fifteen cases among which improvement was noticed in six cases (two after levodopa withdrawal, two despite treatment continuation, and two cases lacking details about action taken with levodopa); three cases did not recover; in the remaining six cases, evolution was not known. "Hyperuricemia" was not mentioned in the Summary of Product Characteristics of medicine containing levodopa; however, "abnormality biologics test with uric acid" was mentioned. Despite few cases of recovery after reduced doses of levodopa, the above-described case of positive reintroduction was an argument in favor of the role of levodopa in gout flare. This study highlights a potential association between levodopa and gout through an analysis of the cases reported in the WHO pharmacovigilance database.

A male patient, diagnosed as acute gouty arthritis with hypertension, gastrointestinal fungal infection, gastric ulcer, and other diseases, received the following treatment: low purine diet, alkalization of urine, omeprazole to inhibit gastric acid secretion, low-dose colchicine to relieve joint pain, febuxostat to reduce uric acid synthesis, losartan potassium to reduce blood pressure, atorvastatin calcium tablet to lower lipid, cefmendoxime proxetil to resist infection, and TNF-α antagonist etanercept 25 mg subcutaneous injection two times a week (with 72 hours interval) for two weeks. As a result, the patient responded well to TNF antagonist etanercept. The joint pain was significantly relieved one day after treatment and completely relieved after five days. Two weeks later, the results of C-reaction protein (CRP) and blood routine examination returned to normal. We drawed conclusions as follows: TNF antagonists etanercept can alleviate the acute inflammatory response of gouty arthritis and ensure uric acid-lowering therapy. However, the safety and effectiveness of the drug in the treatment of acute, complex, and refractory gout still need to be confirmed by randomized, multi-center, large sample clinical controlled study. This case report only supplies a new reference scheme for the treatment of similar diseases.

This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF). Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%). Nine studies, which included seven different types of groups, were eligible for analysis. The “untreated uricemia” group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the “no uricemia” group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08–1.89)). The “start-allo” group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the “untreated uricemia” group (RR (95% CI), 0.68 (0.45–1.01)). However, in the “start-allo” group the SUCRA value was comparable to that in the “no uricemia” group (SUCRA: 65.4% for “start-allo”; 64.1% for “no uricemia”). Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.

Background and objectives Several clinical practice guidelines noted the potential benefits of urate-lowering therapy on cardiovascular disease and CKD progression; however, the effect of this regimen remains uncertain. In this systematic review, we aimed to evaluate the efficacy of urate-lowering therapy on major adverse cardiovascular events, all-cause mortality, kidney failure events, BP, and GFR. Design, setting, participants, & measurements We systematically searched MEDLINE, Embase, and the Cochrane databases for trials published through July 2020. We included prospective, randomized, controlled trials assessing the effects of urate-lowering therapy for at least 6 months on cardiovascular or kidney outcomes. Relevant information was extracted into a spreadsheet by two authors independently. Treatment effects were summarized using random effects meta-analysis. Results We identified 28 trials including a total of 6458 participants with 506 major adverse cardiovascular events and 266 kidney failure events. Overall urate-lowering therapy did not show benefits on major adverse cardiovascular events (risk ratio, 0.93; 95% confidence interval, 0.74 to 1.18) and all-cause mortality (risk ratio, 1.04; 95% confidence interval, 0.78 to 1.39) or kidney failure (risk ratio, 0.97; 95% confidence interval, 0.61 to 1.54). Nevertheless, urate-lowering therapy attenuated the decline in the slope of GFR (weighted mean difference, 1.18 ml/min per 1.73 m2 per year; 95% confidence interval, 0.44 to 1.91) and lowered the mean BP (systolic BP: weighted mean difference, −3.45 mm Hg; 95% confidence interval, −6.10 to −0.80; diastolic BP: weighted mean difference, −2.02 mm Hg; 95% confidence interval, −3.25 to −0.78). There was no significant difference (risk ratio, 1.01; 95% confidence interval, 0.94 to 1.08) in the risk of adverse events between the participants receiving urate-lowering therapy and the control group. Conclusions Urate-lowering therapy did not produce benefits on the clinical outcomes, including major adverse cardiovascular events, all-cause mortality, and kidney failure. Thus, there is insufficient evidence to support urate lowering in patients to improve kidney and cardiovascular outcomes.

Background/Objective Pegloticase is used for treatment of refractory gout, which has failed maximal medical management, but only 42% of patients respond completely to treatment because of the presumed development of antidrug antibodies, which rapidly clear the pegloticase molecule. Immunomodulatory medications temper antidrug antibody development in other diseases. The aim of this case series was to investigate the utility of adding methotrexate to a pegloticase regimen to increase the response durability in a real-world practice setting. Methods In this multicenter, proof-of-concept, observational case series, refractory tophaceous gouty arthropathy patients being started on pegloticase 8 mg every 2 weeks were identified. The patients began oral methotrexate 15 mg/wk and folic acid 1 mg/d, 1 month prior to the initial pegloticase administration, and continued throughout pegloticase treatment. Responders were defined by demonstrating ≥80% of preinfusion serum uric acid (sUA) levels

This review aims to critically present the available clinical evidence supporting the treatment of chronic hyperuricemia with xanthine oxidase inhibitors. For this reason, the studies published on uric acid (UA)-lowering drugs in the English language from 2000 to August 2019 have been carefully reviewed. The terms “serum uric acid,” “xanthine oxidase,” “allopurinol,” “febuxostat,” and “topiroxostat” were incorporated into an electronic search strategy, alone and in combinations, in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). Even if new urate-lowering drugs seem of particular efficacy for acute treatment of refractory hyperuricemia, their use is supported by relatively small clinical evidence. On the contrary, large long-term clinical trials have demonstrated that xanthine oxidase inhibitors (XOIs, namely, allopurinol and febuxostat) are effective, safe, and relatively well-tolerated in most of the patients. They have mainly been tested in the elderly, in patients affected by chronic diseases such as heart failure and cancer, and in patients taking a large number of drugs, confirming their safety profile. Recent data also show that they could exert some positive effects on vascular health, renal function, and glucose metabolism. Their cost is also low. In conclusion, XOIs remain the first choice of UA-lowering drug for chronic treatment.

Patients with gout in Nepal are usually attended by medical graduates, family medicine, internists, and orthopedic surgeons. The study aimed to evaluate knowledge, attitude, and practice (KAP) of point-of-care clinicians of Nepal regarding diagnosis and management of gout and assess the quality of treatment provided to the patients. A web-based descriptive, cross-sectional study was conducted among doctors managing gout patients. The questionnaire comprises 38 multiple choice questions; 9 questions for demographic data, 8, 11, and 10 questions each for knowledge, attitude, and practice, respectively. A pilot study was conducted to observe comprehensibility of the questionnaire before subjecting it to the participants. Ethical approval was obtained from review committee of National Center for Rheumatic diseases, Nepal. Simple descriptive statistics was used to describe the correct responses. Among 1200 clinicians invited, 32% (380) participated in the survey. Maximum respondents were of age group 25-45 years (82%) with majority being internists (43%). Although only 32% understood that the disease is not curable, knowledge regarding disease was acceptable in majority (60-90%). Around 83% denied attending any gout-related seminars and 34% denied being updated with the recent guidelines. The majority of postgraduates (72%) managed the cases themselves. Although there was acceptable practice accuracy on use of therapy for acute attacks (75%), target urate levels (57%), and use of urate-lowering agents (92%), they lacked in adequate screening of co-morbidities and initiation of long-term treatment. The point-of-care clinicians have adequate knowledge to diagnose and treat acute events. However, there is poor reflection in practice and frequent update of treatment guidelines is warranted.

Objective\ud To investigate the existence of distinct classes of gout flare trajectories and compare their gout‐specific, comorbid, and sociodemographic characteristics.\ud \ud Methods\ud In a prospective cohort study, adults with gout who were registered with 20 general practices self‐reported the number of gout flares experienced at baseline and after 6, 12, 24, and 36 months via postal questionnaires. Latent class growth analysis (LCGA) was used to identify distinct gout flare trajectory classes. Statistical criteria and clinical interpretability were used to decide the optimal number of classes. Baseline comorbidities, medications, and sociodemographic and gout‐specific characteristics of members of each class were described.\ud \ud Results\ud A total of 1,164 participants (mean ± SD age 65.6 ± 12.5 years; 972 [84%] male) were included. Six latent gout flare trajectory classes were identified: “frequent and persistent” (n = 95), “gradually worsening” (n = 276), “frequent then improving” (n = 14), “moderately frequent” (n = 287), “moderately frequent then improving” (n = 143), and “infrequent” (n = 349). The “frequent and persistent” trajectory had the most class members classified as obese and, along with the “gradually worsening” class, the highest proportion who were socioeconomically deprived. The “frequent and persistent,” “gradually worsening,” and ”frequent then improving” classes had the highest proportions of class members with an estimated glomerular filtration rate

Increased uric acid levels have been known to be associated with different cardiovascular and renal diseases. Over the past few years, several studies have examined the role of urate-lowering therapy (ULT) in hypertension and major adverse cardiac events (MACE) and suggest a potential role of elevated serum uric acid as an independent cardiovascular risk factor. This meta-analysis was done to determine the association of 2 ULTs commonly used in clinical practice (febuxostat vs. allopurinol) on hypertension and MACE and resolve the conflicting results of the outcomes of earlier studies. Randomized controlled trials comparing febuxostat versus allopurinol published with outcomes on blood pressure, all-cause mortality, myocardial infarction (MI), and stroke were searched through PubMed, Google Scholar, and Cochrane database. A total of 10 studies were subsequently included in the meta-analysis. Pooled analysis of the mean differences (MD) were done for the outcomes on blood pressure (systolic and diastolic) and risk ratios (RRs) for the outcomes on MACE with corresponding 95% confidence intervals (CIs). Pooled analysis of studies on hyperuricemic patients showed that febuxostat 40 mg has no significant difference compared with allopurinol 100/300 mg with respect to diastolic (MD, -0.56 with 95% CI of -4.28 to 3.15) and systolic blood pressure (MD, 0.30 with 95% CI of -3.33 to 3.93). No significant differences were also noted on all-cause mortality (RR, 1.18 with 95% CI of 0.99-1.41), MI (RR, 0.92 with 95% CI of 0.72-1.18), and stroke (RR, 1.05 with 95% CI of 0.77-1.43). The results of this meta-analysis showed that the 2 ULTs (febuxostat vs. allopurinol) have no significant association with respect to blood pressure among adult patients with hyperuricemia. No significant association was also noted of either ULT with all-cause mortality, MI, and stroke.

Objective Urate-lowering treatment (ULT) is recommended in gout management. However, initiation of ULT during an acute gout flare is still inconclusive. This study aimed to evaluate the efficacy and safety of the ULT febuxostat administered at initiation of an acute gout attack. Methods A prospective randomized controlled clinical trial was conducted for 12 weeks in primary gout patients who were admitted with acute gout attacks. Subjects were randomly assigned to the febuxostat group in which febuxostat, 40 mg daily, was administered in the primary care setting for attacks, or to the control group in which febuxostat, 40 mg daily, was administered after the attacks. All patients received adequate anti-inflammatory and analgesic therapies. Serum urate (SU) levels were monitored throughout the study. Pain, measured using a visual analogue scale (VAS), and gout recurrence rate were used as primary outcomes. Flare-related inflammation biomarkers were selected as secondary outcomes. Results Fifty-two patients completed the study (febuxostat group: n = 28; control group: n = 24). No significant differences were detected in VAS scores between the two groups over the first 14-day observation period (P > 0.05). Administration of febuxostat decreased SU levels significantly during the first 2-week period. However, the gout recurrent rate or gout flare-related inflammation indicators did not change in the febuxostat or control groups. Treatment-related adverse events were mild and similar between groups. Conclusion Initiation of the urate-lowering drug febuxostat during an acute gout attack caused no significant difference in daily pain, recurrent flares, or adverse effects. The treatment significantly decreased SU levels in the early stage and might have potential long-term benefits in these patients.

To assess rheumatologists' views and practices related to shared decision-making (SDM) in gout treatment. We performed a cross-sectional electronic survey of rheumatologists at U.S. Veterans Affairs (VA) medical centers, assessing views and practices related to SDM in gout. Of the 154 VA rheumatology providers eligible, 90 responded (response rate, 58%). Fifty-eight percent were female, the mean age was 51 years (standard deviation, 9.6), 42% had > 20 years of experience in medical practice. Rheumatologists reported routinely offering a choice to their patients for (1) starting urate-lowering therapy (ULT) for gout vs. doing nothing (70%); (2) choosing NSAIDs, corticosteroids, or colchicine for the treatment of acute flares (67%); and (3) choosing NSAIDs, corticosteroids, or colchicine for anti-inflammatory prophylaxis when starting ULT (51%). Very few rheumatologists offered choice regarding (4) choosing allopurinol vs. febuxostat as the first ULT (16%) and (5) taking daily ULT long-term vs. intermittently (15%). Rheumatologists perceived that a large proportion of patients were often or sometimes unsure of the best choice for these five decisions, 34%, 76%, 76%, 52%, and 54%, respectively. Similar proportions of rheumatologists felt that patients were uninformed about both medication benefits and risks, unclear about the personal importance of the benefits and risks, and unsupported in decision-making. For the five decisions respectively, rheumatologists supported SDM with patients in 76%, 56%, 58%, 27%, and 25%. The majority of VA rheumatologists incorporated SDM in several gout treatment decisions. Rheumatologists also recognized that patients need better support to participate in SDM in gout. Key Points: • Rheumatologists offered shared decision-making to gout patients for 3 key treatment decisions. • Rheumatologists perceived that many patients were unsure of the best choice for these decisions. • Rheumatologists felt that patients were uninformed about medication benefits/risks and unsupported in decision-making.

Objective To determine the incidence and prevalence of gout in the general population and the utilisation of urate-lowering therapy (ULT) among patients with gout in Hong Kong. Methods A total of 2,741,862 subjects who attended any outpatient clinics or accident and emergency department (with or without hospitalisation) in 2005 and did not die before 2006 were identified from the Clinical Data Analysis and Reporting System (CDARS) of the Hospital Authority in Hong Kong. All subjects were followed until the end of 2016 or death. Demographics, diagnosis of gout, serum urate levels, and ULT prescriptions were retrieved from CDARS. Gout was defined by the diagnosis codes in CDARS. The serum urate levels achieved after prescribing ULT were the means of all serum urate levels measured 6 months after prescriptions. Results were analysed by R version 3.3.3 with package ‘prevalence’ version 0.4.0. Results The crude incidence of gout increased from 113.05/100,000 person-years (PY) in 2006 to 211.62/100,000 PY in 2016. The crude prevalence of gout increased from 1.56% in 2006 to 2.92% in 2016. Only 25.55% of patients with gout were prescribed ULT in 2016. 35.8% of patients treated with ULT were able to achieve the target serum urate level of Conclusions Population ageing as well as other risk factors contributed to an increase in the incidence and prevalence of gout in Hong Kong. In 2016, the crude prevalence of gout in Hong Kong was comparable to that in many western countries. However, only one in four patients with gout in Hong Kong was prescribed ULT.