Frequency Of Gout Flares Research Articles

Treatment-Emergent Major Adverse Cardiovascular and Thromboembolic Events were Infrequent During Clinical Trials of Pegloticase.

Long-term maintenance of serum urate (SU) levels <6 mg/dl reduces gout flare frequency. However, urate-lowering therapy (ULT) initiation can induce gout flare. The incidence of thromboembolic (TE) and cardiovascular (CV) events has been shown to increase in the 30 and 120 days following gout flare, respectively; therefore, the question of ULT initiation increasing patient risk for CV/TE events has been raised. Here, we investigate CV/TE event incidence following pegloticase initiation in clinical trials. This post hoc analysis of pooled data from 4 trials examined treatment-emergent gout flare and CV/TE events in patients with uncontrolled gout. Studies included two phase 3 trials (NCT00325195), the MIRROR open-label trial (NCT03635957), and the MIRROR randomized controlled trial (NCT03994731). Per protocol, pegloticase (8 mg) was administered every 2 (all trials) or 4 weeks (phase 3 trials); data from the first 24 weeks of therapy were included in this analysis. Some MIRROR patients received methotrexate (15 mg/week) as co-therapy. Based on prior studies, the high-risk window for CV/TE events was defined as 120 days following flare onset. Overall, 5/328 (1.5%) patients experienced ≥1 CV/TE event during pegloticase treatment, including 3/244 (1.2%) patients who received on-label (biweekly) dosing (35.4 events/1000 person-years). All events occurred within the 120-day gout flare exposure window. CV/TE event incidence during pegloticase treatment was similar to the general gout population (31.7 events/1000 person-years). These findings suggest that pegloticase initiation does not put patients at a higher risk for CV/TE events.

Evaluation of surgical treatment of gout-A retrospective study on 28 cases with tophi.

The efficacy, safety, optimal timing, and urate-lowering effects of surgical interventions in gout management remain poorly understood. This study aims to fill this gap by evaluating the role of surgery in treating gout patients with tophi. A retrospective analysis was conducted on 28 gout patients presenting with tophi. Data were comprehensively retrieved from electronic medical records, including medical history, laboratory findings, surgical procedures, hospitalization duration, postoperative monitoring, and relevant variables. Postoperative improvements were observed in joint symptoms and functionality. Surgical intervention effectively reduced the frequency of gout flares, demonstrating short-term urate-lowering effects (STULE) and potential long-term urate-lowering effects (LTULE) when combined with urate-lowering treatments (ULT). Primary healing occurred in 65 out of 67 surgical sites (97.01%), with only 2 sites (2.99%) experiencing delayed healing, and minimal complications reported. Prolonged hospital stays were associated with elevated leukocyte counts, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels, as well as a higher number of surgical sites, rather than serum uric acid (SUA) levels. Surgical intervention is a promising and safe therapeutic option for managing gout, particularly in cases with joint deterioration, functional impairment, or nerve involvement. Surgery not only reduces the frequency of gout flares but also provides STULE and potential LTULE when complemented with ULT. Patients with lower inflammatory indices and fewer incisions exhibit faster postoperative recoveries. Optimal timing of surgery, ideally during periods of disease remission, is crucial for minimizing complications and reducing hospitalization durations.

Relative Forgiveness of Different Allopurinol Implementation Patterns in People with Gout and their Impact on Clinical Outcomes: a Simulation Study.

Adherence to urate-lowering therapy among people with gout is poor, so it is important to understand which day-to-day medication-taking ('implementation') patterns are most likely to lead to suboptimal serum urate concentrations and worsen clinical outcomes. This study aimed to (1) determine the relative forgiveness (RF) of allopurinol with hypothetical and real-life implementation patterns in people with gout, (2) explore the use of RF as a means of identifying suboptimal implementation patterns, (3) assess the impact of suboptimal implementation patterns on clinical outcomes. A simulation study was conducted using a pharmacokinetic-pharmacodynamic model for allopurinol and serum urate to determine the RF of allopurinol implementation patterns. With 100% ('perfect') implementation, the probability of adequate urate control (> 90% of days with urate < 0.36 mmol/L over 360 days) for a 300 mg dose of allopurinol was 0.549. Simulations based on real-life individual implementation patterns over a year yielded a median RF of 0.51, indicating that half of the patterns studied were at least 50% less likely to achieve adequate urate control than perfect implementation. Our study provides evidence that missing one or two doses of allopurinol, even repeatedly over a year, does not significantly impact serum urate target achievement or clinical outcomes. However, people who take repeated drug holidays of more than 3 days in a row (followed by less than 15 consecutive days of dosing) are less than 0.3 times as likely (at least 70% less likely) to achieve adequate urate control than those with perfect implementation and may see an increase in the frequency of gout flares.

Gout and Nutrition

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

The value of musculoskeletal ultrasound in predicting gout flares in index joints: A prospective cohort study of people with gout starting urate-lowering therapy

ObjectivesTo evaluate whether ultrasound findings of monosodium urate (MSU) crystal deposition predict frequent gout flares in index joints over 12 months. MethodsThis single-center study enrolled people with at least one gout flare involving the MTP1, ankle or knee joint. The most painful or most frequently joint was identified as index joint for analysis. All participants were started on urate-lowering therapy and had an ultrasound scan of the index joints at the baseline visit. OMERACT scores (for tophus, double contour sign and aggregates) were used to analyze whether ultrasound scores predicted frequent (≥2) gout flares in the index joint over 12 months. ResultsFrequent flares were significantly higher in those with ultrasound findings in all index joints (MTP1: tophus: 85.0% vs 46.0%, P < 0.001, aggregates: 78.8% vs 59.0%, P < 0.01; ankle: tophus: 54.6% vs 20.8%, P < 0.001; aggregates: 60.0% vs 35.9%, P < 0.05; knee: tophus: 68.4% vs 28.6%, P < 0.05). For the MTP1, for each 1-point increase in tophus score, the odds of frequent gout flares increased by 5.19 [(95%CI: 1.26–21.41), 7.91 [(95%CI: 2.23–28.14), and 13.79 [(95%CI: 3.79–50.20)] fold respectively. For the ankle, a tophus score of 3 markedly improved the prediction of the frequent flares [OR= 9.24 (95%CI=2.85–29.91)]. Semi-quantitative sum scores were associated with frequent flares with an OR (95%CI) of 13.66 (3.44–54.18), P < 0.001 at the MTP1, 7.05 (1.98–25.12), P < 0.001 at the ankle. ConclusionUltrasound features of MSU crystal deposition at the MTP1 and knee predict subsequent risk of frequent gout flares in the same joints following initiation of urate-lowering therapy, with the highest risk in those with high tophus scores.

The association between gout flares and monosodium urate burden assessed using musculoskeletal ultrasound in patients with gout.

Ultrasound (US) has a high sensitivity in detecting monosodium urate (MSU) deposition in gout patients. However, the value of US in predicting gout flares has been reported only in a few monocentric studies. To investigate the association between gout flares in the previous year and US-detected MSU burden using two different US scores. A retrospective study. Patients with gout were consecutively recruited to undergo musculoskeletal US examinations of their knees, ankles, and feet. The score derived from Outcome Measure in Rheumatology (hereinafter referred to as MSU score) and musculoskeletal US features-based (hereinafter referred to as MSKF score) were used to quantify the MSU burden of gout. Odds ratios for frequent gout flares were calculated. We enrolled 1894 patients with gout (mean age: 45 years; gout duration: 5 years; males: 96.1%), experiencing a median of three flares over the past year. Of these, 428 (22.6%) patients reported frequent (⩾7) gout flares. The MSU and MSKF median scores were 6 and 9, respectively. For each five-point increase in MSU and MSKF score, the odds ratio of frequent gout flares increased 1.13-fold and 1.24-fold, respectively. The area under the curve (AUC) for the MSU and MSKF score was 0.635 [95% confidence interval (CI): 0.604-0.665] and 0.688 (95% CI: 0.659-0.718), respectively, (AUC difference 0.054, p value for AUC difference < 0.001). The MSU and MSKF scores were significantly associated with the number of gout flares in the previous year. The MSKF score outperformed the MSU score in terms of frequent gout flare discrimination.

Sex and country differences in gout: cross-country comparison between Sweden and the UK

Objective Compare characteristics, sex differences, and management of gout in Sweden and the UK. Method The results from two separate primary care gout surveys from Sweden and the UK were compared. Participants aged ≥18 years with gout were sent a questionnaire asking about lifestyle, gout characteristics, uratelowering therapy (ULT), comorbidities, disability, and disease impact. For sex comparison, participants were pooled across countries. Results In total, 784 (80% male) participants from Sweden and 500 (87% male) from the UK were included. Swedish patients were significantly older at gout onset, mean (SD) age 72 (12) versus 63 (13) years, (p<0.0001), with more comorbidities, and more frequent use of ULT (48% vs 35%, p=0.0005, age-adjusted). Use of alcohol and diuretics was significantly more common among UK patients, who also reported a higher number of gout flares, mean (SD) 2.2 (1.7) versus 1.6 (3.6), (p=0.003) age-adjusted. Females with gout were older at gout onset, mean (SD) age 67 (13) versus 56 (15), (p<0.0001), more often obese, and reported higher use of diuretics. Furthermore, females reported greater impact of gout, more pain and physical limitations, whereas no sex differences were seen in ULT or flares. Conclusions In the UK, gout was more frequently associated with modifiable risk factors. People with gout in Sweden were more commonly taking ULT and had lower frequency of gout flares and impact of gout. Females with gout more commonly took diuretics, had higher body mass index, and reported greater physical disability, which should be considered when managing gout in women.

Nutritional factors in the prevention and treatment of gout

Introduction and purpose: Despite the fact that effective urate lowering therapy and anti-inflammatory drugs for the treatment of gout are commonly available, there is considerable interest in novel treatment approaches. Gouty patients often have a multitude of comorbidities, which lead to concern over drug–drug interactions and medication adverse events. Thus, diet modifications are examined as a way of nonpharmacological treatment of gout. In this review, we explore the potential impact of nutritional factors on hyperuricemia and clinical gout outcomes. A search was conducted using PubMed and Google Scholarship databases.&#x0D; Brief description of the state of knowledge: Management in patients with gout should be holistic. Incorrect nutrition may lead to hyperuricemia. Studies to date suggest that avoidance of certain foods and beverages can decrease the frequency of gout flares. Weight loss may be beneficial for prevention as well as treatment of gout and its comorbidities. The impact of various types of diet on the course of gout has been given particular attention and recent research suggests that vegetarian, mediterranean and dash diets may be beneficial for gouty patients. Also, some vitamins and omega-3 PUFA have favorable effects and the potential clinical use in gout treatment.&#x0D; Conclusions: We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients. Although piecemeal modifications of various nutrients often provide incomplete dietary recommendations, understanding the role of nutritional factors in gout development would be helpful for patients in choosing their healthy diet.

The risk of nonalcoholic fatty liver disease in gout patients with frequent flares: a retrospective cohort study.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease that is related to high serum uric acid; however, the association between the frequency of gout flares and NAFLD risk remains unclear. This study aimed to investigate whether frequent gout flares were associated with incident NAFLD and analyze the interaction of frequency of gout flares and Adipo-IR on NAFLD in the gout Chinese population. A total of 350 cases of gout patients were enrolled in this retrospective cohort study. Cox proportional hazard regression analyses were performed to determine the association between frequent gout flares and NAFLD during follow-up and analyze the interaction of frequency of gout flares and Adipo-IR on NAFLD. Receiver operating curves (ROC) were plotted to explore the diagnostic value of frequent gout flares and Adipo-IR on the occurrence of NAFLD. NAFLD developed in 78 participants (22.3%) during follow-up. Logistic regression showed that Adipo-IR was an independent factor associated with frequent gout flares risk. The multivariate Cox regression analysis revealed that frequent gout flares and Adipo-IR were associated with NAFLD risk (HR: 7.88, 95% CI: 2.11-29.48, p < 0.01; HR: 1.058, 95% CI: 1.01-1.2, p < 0.05). And ROC showed that both of them had a great discriminant ability to diagnose NAFLD. Our data showed an independent association between the frequency of gout flares or Adipo-IR and incident NAFLD. Frequent gout flares and elevated Adipo-IR had a good predictive capability towards NAFLD development and played a synergistic role in the development of NAFLD. • Frequent gout flares and elevated Adipo-IR had a good diagnostic capability towards NAFLD development. • Frequent gout flares and Adipo-IR played a synergistic role in the development of NAFLD.

Reliability and Validity of the Korean Version of the Gout Impact Scale.

The Gout Impact Scale (GIS), part of the Gout Assessment Questionnaire 2.0, measures gout-specific health-related quality of life (HRQOL). This study aimed to translate the GIS into Korean and validate the Korean version (K-GIS) using generic HRQOL measures. The GIS was translated into Korean and back-translated into English. We asked patients aged 18 years or older who met the 2015 gout classification criteria to fill out the questionnaires (from January 2022 to June 2022); the K-GIS (5 scales [0-100 scores each]), along with the Korean version of Health Assessment Questionnaire (HAQ) and EuroQol-5 dimension (EQ-5D). We investigated the internal consistency, construct validity, and discriminative validity for gout characteristics of K-GIS. The K-GIS form was administrated to patients 4 weeks later to assess the test-retest reliability using the intraclass correlation coefficient (ICC). One hundred patients completed the questionnaire. The mean ± standard deviation age of the patients was 53.0 ± 15.1 years, and 99.0% of the patients were men. All scales had high degree of internal consistency (Cronbach's α = 0.59 to 0.96) and test-retest reliability (n = 18, ICC = 0.83 to 0.94, all P < 0.001), except for unmet gout treatment needs. Weak-to-moderate correlations were observed between the K-GIS scales and HAQ or EQ-5D (r = 0.21 to 0.46). The K-GIS scores were significantly higher in the presence of bone erosion, absence of urate-lowering therapy, serum urate levels > 6 mg/dL, frequent gout flares in the past year, and fewer comorbidities. In contrast, neither the HAQ nor the EQ-5D could discern these subsets of patients. The K-GIS is a reliable and valid HRQOL measure for patients with gout. Higher K-GIS scores were associated with clinical characteristics leading to unfavorable outcomes, which were not demonstrated by the HAQ and EQ-5D.

Improved joint and patient-reported health assessments with pegloticase plus methotrexate co-therapy in patients with uncontrolled gout: 12-month exploratory outcomes of the MIRROR open-label trial

BackgroundUncontrolled/refractory gout patients are recalcitrant/intolerant to oral urate-lowering therapies (ULTs), experiencing frequent gout flares, functionally limiting tophi, and low quality of life. Pegloticase lowers urate, but anti-pegloticase antibodies limit urate-lowering efficacy and increase infusion reaction (IR) risk. Immunomodulator + pegloticase co-administration may improve treatment response rates, with 79% of MIRROR open-label trial (MIRROR-OL, pegloticase + oral methotrexate) participants meeting 6-month response criteria. Exploratory outcomes from MIRROR-OL are described here.MethodsAdults with uncontrolled gout (serum urate [SU] ≥ 6 mg/dL and ULT-intolerance/recalcitrance or functionally limiting tophi) were included. Oral methotrexate (15 mg/week) was administered 4 weeks before and during pegloticase treatment (biweekly 8 mg infusion, ≤ 52 weeks). Exploratory outcomes included change from baseline (CFB) in number of affected joints, Health Assessment Questionnaires (HAQs), and Gout Global Assessments.ResultsFourteen patients received ≥ 1 pegloticase infusion, with 13 included in 52-week analyses (1 enrolled before treatment-extension amendment, exited at 24 weeks). Three patients prematurely exited due to SU rise; 10 completed 52-week evaluations (8 completed 52 weeks of co-therapy, 2 completed 24 weeks [met treatment goals]). At 52 weeks, SU averaged 1.1 ± 2.5 mg/dL, with improvements in HAQ pain and health (CFB: − 33.6 and − 0.7, respectively), Patient and Physician Global Assessments (CFB: − 4.6 and − 5.7, respectively), and joint involvement (CFB: − 5.6, − 8.4, − 6.0 tender, swollen, tophi-affected joints, respectively). Two patients underwent dual-energy computed tomography, showing concomitant monosodium urate volume reductions. All patients had ≥ 1 AE, with 92.9% experiencing acute flare. One mild IR (“cough”) occurred and no new safety signals were identified.ConclusionPegloticase + methotrexate co-therapy resulted in sustained SU-lowering with meaningful improvements in clinical measures, urate burden, and patient-reported outcomes.Trial registrationClinicalTrials.gov (NCT03635957)

Gout and Diet: A Comprehensive Review of Mechanisms and Management.

Gout is well known as an inflammatory rheumatic disease presenting with arthritis and abnormal metabolism of uric acid. The recognition of diet-induced systemic metabolic pathways have provided new mechanistic insights and potential interventions on gout progression. However, the dietary recommendations for gouty patients generally focus on food categories, with few simultaneous considerations of nutritional factors and systemic metabolism. It is worthwhile to comprehensively review the mechanistic findings and potential interventions of diet-related nutrients against the development of gout, including purine metabolism, urate deposition, and gouty inflammation. Although piecemeal modifications of various nutrients often provide incomplete dietary recommendations, understanding the role of nutritional factors in gouty development can help patients choose their healthy diet based on personal preference and disease course. The combination of dietary management and medication may potentially achieve enhanced treatment effects, especially for severe patients. Therefore, the role of dietary and nutritional factors in the development of gout is systematically reviewed to propose dietary modification strategies for gout management by: (1) reducing nutritional risk factors against metabolic syndrome; (2) supplementing with beneficial nutrients to affect uric acid metabolism and gouty inflammation; and (3) considering nutritional modification combined with medication supplementation to decrease the frequency of gout flares.

Role of diet in hyperuricemia and gout.

Gout is the most common form of inflammatory arthritis, affecting 41 million adults worldwide. The global burden of gout has been increasing over the last three decades, yet its management remains suboptimal. The primary aim of this manuscript is to review the impact of various diets such as the DASH, Mediterranean, and low purine diets; weight loss; and individual foods, including alcohol, caffeine, cherry, dairy, high-fructose corn syrup, omega-3 fatty acids, and vitamin C on hyperuricemia and clinical gout outcomes such as flares and tophi. Few studies to date have specifically evaluated the effect of various dietary approaches on hyperuricemia among people with gout and on gout-specific outcomes. Overall, the dietary factors appear to have a small effect on serum urate levels, and their impact on the long-term clinical course of gout is uncertain. Limited evidence suggests that avoidance of certain foods and beverages may decrease the frequency of gout flares. Weight loss may be beneficial for prevention as well as treatment of gout. Urate-lowering therapy remains the mainstay of therapy, with diet and dietary factors studied to date playing a limited role in the definitive management of gout.

Новые рекомендации Американской коллегии ревматологов по ведению больных подагрой (2020). Комментарии к некоторым позициям

In May 2020, the updated recommendations of the American College of Rheumatology on the patient management with gout were published. The focus was on the indications for urate-lowering therapy (ULT) and its optimal use, treatment of gout flares, and the importance of lifestyle. A consensus based on current literature and patient preferences resulted in 42 recommendations. The sixteen highly recommended provisions included the following: ULT should be prescribed to all patients with tophi, radiological signs of joint damage or frequent gout flares; allopurinol should be preferred as a ULT first-line drug, including for patients with chronic kidney disease (CKD) above stage III; ULT regimen should begin at a low initial dose of allopurinol (&lt;100 mg/day and below in CKD) or febuxostat (&lt;40 mg/day); the treatment tactics should achieve the goal with dose titration under the control of the serum uric acid (SUA) level to maintain &lt;6 mg/dL (&lt;360 mmol/L). At the beginning of treatment, concomitant anti-inflammatory prophylactic therapy of at least 3–6 months was strongly recommended. Colchicine, nonsteroidal anti-inflammatory drugs or glucocorticoids (oral, intra-articular, or intramuscular) were suggested for the treatment of gout flares. The purpose of this publication was to inform physicians decision-making on the gout treatment about the patient management algorithm and the need to achieve the target level of SUA to prevent flares and complications of the disease. KEYWORDS: gout, hyperuricemia, clinical recommendations, urate-lowering therapy, diet, lifestyle, food, treatment. FOR CITATION: Gromova M.A., Tsurko V.V. New recommendations of the American College of Rheumatology for the patient management with gout (2020). Review on some points. Russian Medical Inquiry. 2021;5(2):89–95. DOI: 10.32364/2587-6821-2021-5-2-89-95.

2020 American College of Rheumatology Guideline for the Management of Gout.

To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

2020 American College of Rheumatology Guideline for the Management of Gout.

To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations. Fifty-seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta-analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional. Forty-two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat-to-target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3-6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended. Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.

P142 Factors associated with change in health-related quality of life in people living with gout: a three-year prospective cohort study in primary care

Abstract Background Gout affects 2.5% of adults in the UK but is often poorly managed. It can impair health-related quality of life (HRQOL), yet little is known about which people with gout are at risk of worse outcomes. We investigated factors associated with change in HRQOL over a three-year period in people living with gout in primary care. Methods People with gout registered with 20 general practices in the West Midlands completed the Gout Impact Scale (GIS), Short-Form-36 Physical Function subscale (PF10) and health assessment questionnaire disability index (HAQ-DI) at five time-points (baseline &amp; 6, 12, 24 and 36 months) via postal questionnaire. Linear mixed modelling (LMM) with multivariate adjustment for baseline and time-varying covariates was used to investigate gout-specific, comorbid and socio-demographic factors associated with change in the Concern Overall (GIS-CO), PF10 and HAQ-DI over three years. Higher scores are worse for GIS-CO and HAQ-DI, but better for PF10. Results Of 1,184 baseline respondents, 818 (80%), 721 (73%), 696 (75%), 605 (68%) responded at 6, 12, 24 and 36 months respectively. Mean age (SD) at baseline was 65.6 (12.5) years. 990 (84%) were male, 494 (42%) reported &amp;gt;2 gout flares in the previous year, 624 (54%) were taking allopurinol and 318 (27%) had an eGFR&amp;lt;60mL/min/1.73m2. Factors identified as being associated with a deterioration in HRQOL over three years (table), were gout flare frequency (GIS-CO, PF10), history of oligo/polyarticular flares (GIS-CO, HAQ-DI), having a flare currently (GIS-CO), allopurinol use (PF10), having body pain (GIS-CO, PF10, HAQ-DI), higher pain severity (GIS-CO, PF10, HAQ-DI), number of comorbidities (PF10), eGFR &amp;lt;60mL/min/1.73m2 (PF10, HAQ-DI), anxiety (GIS-CO), depression (PF10, HAQ-DI), and older age (PF10, HAQ-DI). Factors associated with an improvement in HRQOL were longer gout duration (GIS-CO), older age (GIS-CO), lower socioeconomic deprivation (PF10, HAQ-DI) and more frequent alcohol consumption (PF10, HAQ-DI). Conclusion Gout-specific, comorbid and socio-demographic factors associated with change in HRQOL over a three-year period in people living with gout in primary care were identified, highlighting people at risk of worse outcomes over three years and at greatest need of urate-lowering therapy and other targeted interventions. Disclosures L. Watson None. J. Belcher None. E. Nicholls None. P. Chandratre None. M. Blagojevic-Bucknall None. S. Hider None. S.A. Lawton None. C.D. Mallen None. S. Muller None. K. Rome None. E. Roddy None.

Pleiotropic effect of the ABCG2 gene in gout: involvement in serum urate levels and progression from hyperuricemia to gout

BackgroundThe ABCG2 Q141K (rs2231142) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~ 60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout by testing for association of ABCG2 rs2231142 and rs10011796 with gout using HU controls.MethodsWe analysed 1699 European gout cases and 14,350 normouricemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables.ResultsIn Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR = 1.85, P = 3.8E− 21 and ORmeta = 1.85, P = 1.3E− 03, respectively). There was evidence for an effect of 141K in determining HU in European (OR = 1.56, P = 1.7E− 18) but not in Polynesian (ORmeta = 1.49, P = 0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR = 1.37, P = 4.7E− 06), however significantly weaker than ABCG2 rs2231142 141K (PHet = 0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796. Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian (P = 0.009) and 2.6-fold in European (P = 9.9E− 06). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian (Pmeta = 2.5E− 03).ConclusionThese data are consistent with a role for ABCG2 141K in gout in the presence of established HU.

Risk factors of ultrasound-detected tophi in patients with gout.

Tophus is a characteristic manifestation of advanced gout, the clinical significance of which is often underestimated. This study aimed to compare the difference of clinical and ultrasound features between gout patients with and without ultrasound-detected tophus and identify risk factors associated with the presence of ultrasonographic tophus in gout patients. A total of 85 gout patients were divided into tophaceous (n = 54) and non-tophaceous group (n = 31) according to the presence of ultrasound-detected tophus. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joint (MTP1). Clinical information and ultrasound findings were compared between the groups. A multivariate logistic regression analysis to determine possible risk factors is associated with the number of ultrasound-detected tophaceous joints. Older age, longer gout duration, higher gout flare frequency, lower estimated glomerular filtration rate (eGFR), and higher prevalence of hypertension, hyperlipidemia, and ultrasound manifestations including double contour sign (DCS) and erosion were observed in tophaceous patients from the univariate analysis. Multivariable logistic regression analysis showed that eGFR and disease duration were independently associated with the number of tophaceous joints. Lower eGFR and longer course duration were associated with a higher risk of tophi (B = -0.020, 0.141; P = 0.009, 0.010, respectively). The main factors that may influence the formation of tophi are disease duration and eGFR.Key Points• Lower eGFR and longer course duration are independent risk factors of tophi formation in gout patients.• The incidence of ultrasound manifestations including double contour sign (DCS) and erosion in patients with tophi were higher than those without tophi.

Lack of effect of tart cherry concentrate dose on serum urate in people with gout.

Cherry concentrate has been suggested to reduce serum urate (SU) and gout flares. The aims of this study were to determine the magnitude of the effect of tart cherry concentrate on SU in people with gout, the most effective dose of tart cherry concentrate for lowering SU, and adverse effects. Fifty people with gout and SU > 0.36 mmol/l were recruited. Half were on allopurinol and half were on no urate-lowering therapy. Participants were randomized to receive tart cherry juice concentrate: placebo, 7.5 ml, 15 ml, 22.5 ml or 30 ml twice daily for 28 days. Blood samples were taken at baseline, then at 1, 3 and 5 h post cherry and then on days 1, 3, 7, 14, 21 and 28. The area under the curve for SU was calculated over the 28-day study period. Cherry concentrate dose had no significant effect on reduction in SU area under the curve, urine urate excretion, change in urinary anthocyanin between day 0 and day 28, or frequency of gout flares over the 28-day study period (P = 0.76). There were 24 reported adverse events, with only one (hyperglycaemia) considered possibly to be related to cherry concentrate. Allopurinol use did not modify the effect of cherry on SU or urine urate excretion. Tart cherry concentrate had no effect on SU or urine urate excretion. If there is an effect of cherry concentrate on gout flares over a longer time period, it is not likely to be mediated by reduction in SU. Australian New Zealand Clinical Trials Registry (ANZCTR), https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368887, ANZCTR 12615000741583).