Effect of Clinical Typing on Serum Urate Targets of Benzbromarone in Chinese Gout Patients: A Prospective Cohort Study

IntroductionAchieving a goal of serum urate levels in patients with gout is an important way to prevent gout and its complications while it remains difficult with a low targeting rate worldwidely. Currently, hyperuricemia classification has not been widely applied to the management of gout owing to insufficient clinical evidences. This study aimed to evaluate the effectiveness of achieving target urate based on hyperuricemia classification in Chinese patients with gout.MethodsIn this prospective study, patients with gout receiving urate lowering therapy with benzbromarone were assigned to two groups, a renal underexcretion and an unclassified type. The primary endpoint was the proportion of patients achieving the serum urate target (<360 μmol/L) during the 12-week study. The frequency of acute gout attacks as well as physical and chemical indicators were secondary endpoints.ResultsTarget serum urate level was achieved in 60.5% of underexcretors compared with 39.0% of patients of the unclassified type at week 12 (P = 0.002). Blood glucose and cholesterol levels were lower in the underexcretor group compared with the unclassified type group at the end of the trial, without significant different frequencies in gout flare during the study. In subgroup analysis, stratified by body mass index and estimated glomerular filtration rate, the proportion of patients with serum urate <360 μmol/L was greater in the underexcretion compared with the unclassified type group.ConclusionsThe increased achievement of target serum urate in the underexcretion group supports the use of a clinical hyperuricemia typing treatment strategy for gout.

Disease Modification in Gout: A Qualitative Study of Gout Expert Rheumatologists

Objective To examine healthcare provider views of disease modification in gout to potentially derive a provisional set of domains for disease modification in gout. Methods We performed a qualitative nominal group (NG) study with 20 gout experts (15 were authors/expert panel members of the 2012 and/or 2020 ACR gout guidelines, and/or 2015 ACR/EULAR gout classification criteria) about what constitutes “disease modification” in gout – “What sorts of things do you think constitute a change in the course of disease in gout? (positive); What are all the ways in which gout as a disease can be modified?” Results Decrease in gout flares was rated #1 rank in all six NGs as indicative of disease modification in gout, followed by serum urate (SU) lowering, which was rated #1 rank in 1 of the 6 NGs (tied score with flares in one NG). Other components of gout disease modification were to improve quality of life/productivity; restore function; reduce/eliminate pain; reduce tophi burden; and joint preservation or resolution of joint damage. Potential additional components that were not ranked in the top 3 votes within each NG were: Decrease healthcare cost/utilization; cardiovascular/renal morbidity/mortality reduction; and stop urate crystals formation. Conclusion This qualitative study provides a provisional set of domains for disease modification in gout. Future studies for the development of thresholds for disease modification domains, and wider consensus on this definition are needed.

Diagnosis and Treatment of Gout Arthritis

Gout is a heterogeneous, often familial, metabolic disease associated with abnormal deposits of uric acid in tissues and initially characterized by recurrent acute arthritis, usually monoarticular, and later by chronic deforming arthritis. Urate deposition occurs when serum uric acid is saturated (that is, at greater than 6.8 mg/dL [404.5 mcmol/L]). Hyperuricemia is caused by excess or underexcretion of uric acid, sometimes both. The disease is especially common in the Pacific islands, for example, the Philippines and Samoa. Acute gouty arthritis is sudden in onset and often occurs at night. It may develop without a clear precipitating cause or may follow a rapid increase or decrease in serum urate levels. Common precipitants are excess alcohol (especially beer), changes in medications that affect urate metabolism, and, in hospitalized patients, fasting before medical procedures. This literature review presents gout arthritis, symptoms and signs in general to the prognosis of this disease.

Efficacy And Renal Safety of Febuxostat In Management of Gout And Chronic Kidney Disease: A Retrospective Study

Background: Elevated serum urate levels are associated with renal deterioration of chronic kidney disease (CKD). Whether urate-lowering treatment with febuxostat can improve renal function or attenuate the decline of the estimated glomerular filtration rate (eGFR) is controversial. The current study sought to explore efficacy and renal safety of febuxostat in gout patients with CKD and explore factors correlated with target serum urate (sUA).Methods: The current study was a single-center retrospective study comprising male gout patients with CKD. sUA, the rate of sUA < 360 µmol/L and renal safety were analyzed in subjects who had been treated with febuxostat for more than 44 weeks. Factors correlated with target sUA were explored by logistic regression analysis. Results: A total of 87 patients who had been diagnosed with gout and CKD met the inclusion criteria for the study. Twenty-five (28.73%) patients presented with stage 2 CKD, 58 (66.67%) were diagnosed with stage 3 CKD and 4 (4.60%) were diagnosed with stage 4 CKD. Analysis of sUA level showed a significant reduction at week 44~ (598.22 ± 95.11 µmol/L vs. 429.76 ± 123.45 μmol/L; P < 0.05), and the RAT increased to 34.50%. eGFR level of all patients was 52.37 ± 11.74 ml/min/1.73cm2 at baseline and 56.51 ± 15.01 ml/min/1.73cm2 at week 44~ (P < 0.05). The findings showed improvement of eGFR level in different stages of CKD, mainly in stage 3 CKD patients (P < 0.05). After stratification based on risk factors of hypertension, diabetic mellitus, hyperlipidemia and the usage of Non-Steroidal Anti-inflammatory Drugs (NSAIDs), the findings showed that eGFR levels of patients with ≤ 1 risk factors showed significant improvement (P < 0.05). Logistic regression analysis indicated that baseline sUA level and acute arthritis were correlated with the RAT in gout and CKD patients treated with febuxostat.Conclusions: In this retrospective study, febuxostat demonstrated effective and renal safety in gout patients with CKD. Baseline sUA level and acute arthritis may affect achieving of target sUA.

Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis

Aims To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients. Methods and results Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT’s a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT’s and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l). Conclusions Data from RCT’s and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia. Systematic review registration PROSPERO registration CRD42018089744

Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.

SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) in African American veterans with gout: a trial study protocol

Objective Medication adherence in gout is suboptimal, and the lack of effective interventions to address it presents a huge challenge. Medication adherence and gout outcomes are worse in racial/ethnic minorities. The objective of this paper was to provide the details of the study protocol for randomized, controlled trial (RCT) in African Americans (AAs) with gout that will test the effectiveness of a culturally appropriate gout storytelling intervention. Methods The SToRytelliing to Improve Disease outcomes in Gout (STRIDE-GO) study will be a 12-month, multicenter, open-label RCT that will assess the effect of a culturally appropriate gout storytelling in at least 300 AA veterans with gout. Participants will be randomized to gout-storytelling intervention vs. a stress reduction video in a 1:1 ratio. The primary outcome is urate-lowering therapy (ULT) adherence measured with MEMSCap™, an electronic monitoring system (efficacy, 6 months; sustenance of efficacy, 12 months). Secondary outcomes include gout flares, serum urate (SU), gout-specific health-related quality of life [HRQOL], self-reported ULT adherence, patient satisfaction with treatment, and patient understanding of the intervention. AA veterans with gout who met the 1977 Preliminary American College of Rheumatology (ACR) classification criteria for gout, currently prescribed an oral ULT medication (allopurinol or febuxostat) for at least 6 months, and not using a pillbox to redistribute their medications, will be invited to an in-person study visit. After the study coordinators obtain informed consent, and ensure that participants meet the inclusion criteria, the eligible participants will be provided with their current ULT in a MEMSCap™ bottle for the 1-month run-in period and asked to return to the clinic in 1 month. ULT adherence with MEMSCap™ will be recorded at a 1-month return visit. Interested participants will complete the baseline assessments, randomized using the computerized system to either gout-storytelling intervention or a stress reduction intervention video arm and watch the respective video in-clinic. Patients will be interviewed on the phone at 2 and 4 months regarding the viewing of the videos at home at each time. Participants will be assessed in-clinic at 3, 6, 9, and 12 months; MEMSCap™ data and patient surveys will be captured at each visit. For any missed visit, assessments will be completed on the phone and MEMSCap™ data captured at the next in-clinic visit. Discussion The study will assess the efficacy of a behavioral intervention to improve ULT adherence in minority populations with gout. Trial registration ClinicalTrials.gov NCT 02741700. Registered on 14 September 2018