Initiation Of Urate-lowering Therapy Research Articles

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.

Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

Adherence and Treat-to-Target Benchmarks in Older Adults With Gout Initiating Urate-Lowering Therapy in Ontario, Canada: A Population-Based Study.

We sought to evaluate urate-lowering therapy (ULT) adherence and treatment-to-target (T2T) serum uric acid (SUA) levels among older adults with gout starting ULT. We performed a population-based retrospective cohort study in Ontario, Canada in patients with gout aged ≥66 years newly dispensed ULT between 2010 and 2019. We defined successful T2T as patients having SUA levels <360 μmol/L (6 mg/dL) within 12 months after ULT dispensation. We also assessed adherence to ULT. Multilevel logistic regression clustered by ULT prescriber evaluated patient, physician, and prescription factors associated with reaching target SUA levels. Among 44,438 patients (mean ± SD age 76.0 ± 7.3 years; 64.4% male), 30,057 (67.6%) patients had ≥1 SUA test completed. Overall, 52.3% patients reached SUA target within 12 months, improving from 45.2% in 2010 to 61.2% in 2019 (P < 0.0001). ULT adherence was 55.3% overall and improved annually. Key factors associated with achieving T2T included febuxostat treatment (odds ratio [OR] 11.40, 95% confidence interval [95% CI] 5.10-25.43) (was only dispensed in 88 patients), ULT adherence (OR 5.17, 95% CI 4.89-5.47), allopurinol starting doses >50 mg (OR 2.53, 95% CI 2.14-2.99), colchicine/oral glucocorticoids co-prescription (OR 1.24, 95% CI 1.14-1.34), and ULT prescription from a rheumatologist. Only 52.3% of patients achieved an optimal SUA level within 1 year of ULT initiation. ULT adherence was suboptimal, although improving over time. ULT adherence and higher allopurinol starting doses had the strongest associations of achieving a target SUA level. This study highlights room for improvement in gout management and potential strategies to address care gaps.

Association between urate-lowering therapy initiation and all-cause mortality in patients with type 2 diabetes and asymptomatic hyperuricemia

AimsTo assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). MethodsThis nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. ResultsAmong 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71–0.84), CV mortality (HR 0.86; 95% CI, 0.76–0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64–0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360–420 μmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 μmol/L (HR 0.74; 95% CI, 0.59–0.94) while levels ≤360 μmol/L did not (HR, 0.96; 95% CI, 0.81–1.14), suggesting a U-shaped relationship. ConclusionsInitiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360–420 μmol/L could potentially enhance this reduced mortality.

#1135 Evaluation of the adequacy of urate lowering therapy prescriptions in patients with chronic kidney disease: results from the CKD-REIN cohort

Abstract Background and Aims Urate Lowering Therapy (ULT) is frequently prescribed to patients with chronic kidney disease (CKD). However, these prescriptions are often inadequate when considering kidney function. Studies evaluating the appropriateness of ULT in the CKD population are predominantly cross-sectional. Yet, the evolution and reassessment of prescriptions remain unexplored in this context. This study aims to assess the prevalence of inappropriate ULT prescriptions (whether contraindications or inappropriately high doses) with regard to kidney function in patients with CKD. Method We used 5-year longitudinal data from the CKD-REIN cohort, a nationwide sample of 3033 nephrology outpatients with moderate-to-advanced CKD. Prescriptions for colchicine, used in the treatment of acute gout attacks, and ULT, such as allopurinol and febuxostat, were prospectively recorded. An inappropriate prescription was defined as the reported prescription of either a contraindicated drug, an indicated drug at an inappropriately high dose level, or a non-recommended prescription relative to the patient's eGFR, as estimated with de-indexed CKD-EPI equation and according to the European (or French if not available) summary of product characteristics. For patients initiating ULT during follow-up, uric acid levels were compared six months before and after the initiation of ULT. Results At baseline, 987 (33%) out of the 3033 included patients (mean ± standard deviation age 67 ± 13 years, 65% men) were prescribed ULT, with 781 (26%) receiving allopurinol and 206 (7%) receiving febuxostat. Compared to patients without a prescription for ULT, those with a ULT prescription were more frequently male, older, had lower kidney function, higher cardiovascular comorbidities, and were more commonly prescribed diuretics and inhibitors of the renin-angiotensin system. Moreover, their uric acid levels were lower (patients with ULT prescription 377.0 ± 110.4 µmol/L versus without ULT prescription 456.5 ± 116.4 µmol/L, p &amp;lt; 0.001). Notably, 316 (40%) allopurinol prescriptions were prescribed at inappropriately high dosages, while 77 (37%) febuxostat prescriptions were not recommended (resulting in a total of 393 (40%) inappropriate ULT prescriptions at baseline). Of the 54 colchicine prescriptions, one-third (n = 18) were contraindicated according to kidney function and nine were prescribed “on-demand” for crisis anticipation. During a median follow-up of 5.0 [1st-3rd quartile, 4.0–5.1] years, 253 patients were newly prescribed allopurinol and 176 were newly prescribed febuxostat, 54 (21%) out of 253 new allopurinol prescriptions were at inappropriately high dosages, and 68 (39%) out of the 176 new febuxostat prescriptions were not recommended based on the patient's kidney function (Figure). The majority of initially inappropriate ULT prescriptions (n = 393) remained so during follow-up (274 (70%)). Among the 179 patients initiating ULT during follow-up and with available data on uric acid levels, there was a significant decrease in uric acid levels after ULT initiation compared to before initiation (before: 494.5 ± 146.2 µmol/L versus after 408.5 ± 130.9 µmol/L, p &amp;lt; 0.001). A total of 197 patients had initiated colchicine during follow-up, with 61 (31%) receiving contraindicated prescriptions, and 18 (9%) having “on-demand” prescriptions. Conclusion Our findings emphasize the lack of reassessment of ULT prescriptions during the follow-up of patients with CKD. Colchicine prescriptions in case of severe kidney impairment persist despite contraindications. Further evaluation is required to understand the association between ULT prescriptions and the progression of kidney disease.

Identifying the association between serum urate levels and gout flares in patients taking urate-lowering therapy: a post hoc cohort analysis of the CARES trial with consideration of dropout

ObjectiveTo investigate gout flare rates based on repeated serum urate (SU) measurements in a randomised controlled trial of urate-lowering therapy (ULT), accounting for dropout and death.MethodsWe performed a secondary analysis...

P086 Trends in the Incidence and Management of Gout in England: A Nationwide Study using the OpenSAFELY Platform

Abstract Background/Aims Gout is the most common inflammatory arthritis worldwide, yet one of the worst managed. Few population-level studies have evaluated how the COVID-19 pandemic impacted on incidence, prevalence, management and hospitalisations for people with gout. We investigated this in England using the OpenSAFELY platform. Methods With the approval of NHS England, we conducted a population-level cohort study using primary care and hospital data via the OpenSAFELY platform for 17.9 million adults (40% of England’s population). We analysed the following outcomes between 1 March 2015 and 28 February 2023: 1) incidence and prevalence of recorded gout diagnoses; 2) incidence of hospitalisations with primary admission diagnoses of gout; 3) initiation of urate-lowering therapy (ULT); and 4) serum urate target attainment. Results From 17.9 million adults, there were 246,695 incident gout diagnoses between March 2015 and February 2023. The mean age of diagnosed patients was 61.3 years; 66,265 (26.9%) were female; and 189,035 (90.9%) of 208,050 with available ethnicity data were White. On a background trend of decreasing gout incidence since 2015, new gout diagnoses fell by 31.0% in the first year of the pandemic (from 1.78 to 1.23 diagnoses per 1,000 adults), relative to pre-pandemic. A partial recovery in gout incidence was seen in the years commencing March 2021 and March 2022, but this remained below pre-pandemic levels. Gout prevalence was 3.07% in 2015/16 and 3.21% in 2022/23. Gout hospitalisations decreased by 30.1% in the year commencing March 2020, relative to the preceding year (9.58 vs. 13.7 admissions per 100,000 adults). People presenting with gout during the pandemic did not have more severe disease than those presenting pre-pandemic, but did have proportionately fewer comorbidities. Of 228,095 people with incident gout and available follow-up, 66,560 (29.2%) were prescribed ULT within six months of diagnosis. Of 65,305 ULT initiators with available follow-up, 16,790 (25.7%) attained a urate ≤360 micromol/L within six months of ULT initiation. In interrupted time-series analyses, ULT prescribing improved modestly during the pandemic, relative to pre-pandemic, while urate target attainment was similar. Conclusion The incidence of recorded gout diagnoses in England decreased markedly during the pandemic. No rebound increase in incidence has been observed as of early 2023, suggesting many people remain undiagnosed as a consequence of the pandemic. For patients who were diagnosed during the pandemic, ULT initiation improved modestly relative to before the pandemic; however, absolute levels of ULT initiation and target attainment remain far below an acceptable standard. Importantly, we showed how country-wide, routinely-collected data can be used to map disease epidemiology and monitor care quality for rheumatological diseases. Disclosure M.D. Russell: Honoraria; AbbVie, Biogen, Eli Lilly, Galapagos, Menarini. Grants/research support; from Eli Lilly, Pfizer, Janssen and UCB. J. Massey: None. E. Roddy: None. B. MacKenna: None. S. Bacon: None. B. Goldacre: Grants/research support; Laura and John Arnold Foundation, NIHR, NHS England, Mohn-Westlake Foundation, Wellcome Trust, Good Thinking Foundation, HDRUK, Health Foundation, WHO, MRC, Asthma UK, BLF, National Core Studies. C.D. Andrews: None. G. Hickman: None. A. Mehrkar: Other; former employee and interim Chief Medical Officer of NHS Digital, RCGP representative on GP Data Professional Advisory Group to NHS Digital. A. Mahto: Honoraria; AbbVie, Galapagos. Grants/research support; Educational support from Eli Lilly. A.I. Rutherford: Grants/research support; Educational support from Eli Lilly. S. Patel: None. M.A. Adas: None. E. Alveyn: None. D. Nagra: None. K. Bechman: Grants/research support; Educational support from UCB, and Grants from Versus Arthritis/Pfizer. J.M. Ledingham: Other; BSR President, secretary for The Federation of Joint Royal Colleges of Physicians Specialist Certificate Exam Board, and a trustee of BSR. J. Hudson: None. S. Norton: None. A. Cope: Honoraria; BMS, AbbVie, GSK/Galvini. Grants/research support; BMS. J. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, and UCB.

P085 Implementing treat-to-target urate-lowering therapy during hospitalisations for gout flares: a prospective cohort study

Abstract Background/Aims Hospitalisations for gout flares have doubled in England during the last 15 years. Despite this, no studies have evaluated strategies designed to increase the uptake of urate-lowering therapy (ULT) in people hospitalised for gout flares. Methods We conducted a prospective cohort study in people hospitalised for gout flares. We designed and evaluated an intervention package that consisted of an optimal, in-hospital management pathway based upon BSR, EULAR and ACR guidelines, which encouraged ULT initiation prior to discharge, followed by a nurse-led, post-discharge review. Outcomes including: i) ULT initiation; ii) serum urate target attainment, and iii) re-hospitalisation rates were compared between patients hospitalised for flares in the 12 months post-implementation vs. a retrospective cohort of hospitalised patients from 12 months pre-implementation. Results 119 and 108 patients, respectively, were hospitalised for gout flares in the 12 months before and after the intervention was launched. For patients with six-month follow-up data available (n = 94 and n = 97, respectively), the proportion of patients who were newly initiated on ULT increased to 92% post-implementation, from 49% pre-implementation (age and sex-adjusted odds ratio (aOR) 11.5; 95% CI 4.36-30.5; p &amp;lt; 0.001). More patients achieved a serum urate ≤360 micromol/L within six months of discharge (27% post-implementation vs. 11% pre-implementation; aOR 3.04; 95% CI 1.36-6.78; p = 0.007). The proportion of patients who were re-hospitalised for flares was 9% post-implementation vs. 15% pre-implementation (aOR 0.53, 95% CI 0.22 to 1.32; p = 0.18). Conclusion Following implementation of a strategy designed to optimise care during gout hospitalisations, more than 90% of ULT-naïve patients were initiated on ULT - nearly double the pre-implementation baseline. Despite greater initiation of ULT in the acute flare setting, recurrent hospitalisations did not increase following implementation; supporting the use of ULT in this setting. Improvements were seen in urate target attainment post-discharge; however, focused approaches to optimise ULT dose escalation to achieve target urate levels are required. Disclosure M.D. Russell: Honoraria; AbbVie, Biogen, Eli Lilly, Galapagos, Menarini. Grants/research support; Eli Lilly, Janssen, Pfizer, UCB. L. Ameyaw-Kyeremeh: None. F. Dell'Accio: None. H. Lapham: None. N. Head: None. C. Stovin: None. V. Patel: None. B. Clarke: None. D. Nagra: None. E. Alveyn: None. M.A. Adas: None. K. Bechman: Grants/research support; Versus Arthritis/Pfizer. M.A. de la Puente: None. B. Ellis: None. C. Byrne: None. R. Patel: None. A.I. Rutherford: Other; Educational support from Eli Lilly, UCB. F. Cantle: None. S. Norton: None. E. Roddy: None. J. Hudson: None. A.P. Cope: Honoraria; BMS, AbbVie, GSK/Galvini. Grants/research support; BMS. J.B. Galloway: Honoraria; Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.

P083 Introduction of a gout pathway in a London NHS trust

Abstract Background/Aims Gout is a major cause of morbidity with a significant increase in UK hospitalisation identified over the last decade due to acute flare. Patient and physician education alongside a treat-to-target approach with urate-lowering therapy (ULT) are fundamental in its management. Despite being commonly encountered by clinicians, a survey conducted at Imperial College Healthcare NHS trust (ICHNT) demonstrated 49% of responders did not feel confident managing the condition. This project aimed to create a guideline for the management of acute gout at ICHNT to aid prompt diagnosis and effective management. Increasing the proportion of patients commencing ULT through engagement with local primary care networks was prioritised to improve patient outcomes and reduce subsequent hospital attendances. Methods A trust wide guideline for the management of acute gout was created with input from stakeholders (including emergency and acute medicine physicians) and informed by rheumatology clinicians and current guidelines. Latest recommendations from NICE, BSR and EULAR were consulted alongside local guidelines in place across London. An emphasis was placed upon education and initiation of ULT to improve management of acute and chronic gout to prevent future hospital attendances. Staff within the rheumatology department were consulted to agree on timing of ULT initiation and an effective pathway for implementation. Results Through review of local, national and international guidelines, discrepancies in gout management were identified, most notably variation in the timing of ULT initiation (e.g. during the acute presentation, after flare resolution or after subsequent flare). This was reflected in the practice of clinicians within the rheumatology department at ICHNT. Agreed consensus brought the trust guideline predominantly in line with current NICE guidance for management of acute gout with ULT commenced in patients 2-4 weeks after resolution of flare. Initially, this led to delegation of ULT initiation to general practitioners, however, this resulted in concerns over treatment delays and added pressure on an already stretched service. Follow-up within secondary care was also considered, but capacity issues exist. As a next step, a pilot for a pharmacy-led follow-up service within primary care is planned using standardised protocols supported by secondary care. Conclusion The implementation of a local guideline on the management of acute gout is helpful for clinicians from a non-rheumatology background to facilitate prompt diagnosis and effective management of this common, but often poorly treated, condition. A successful pathway to prevent future flares is more challenging, not only due to discrepancies in current guidelines on timing of ULT initiation but also in creating capacity for follow-up and treatment implementation. This continuing project aims to explore alternative pathways such as a pharmacy-led service that improves patient outcomes and reduces future burden upon healthcare services. Disclosure E. Mabey: None. H. Wilson-Morkeh: None. B. Ellis: None.

Knowledge of and Stated Adherence to the 2020 ACR Guideline for Gout Management: Results of a Survey of US Rheumatologists.

This report evaluates rheumatologists' stated adherence to and agreement with the 2020 American College of Rheumatology (ACR) Guideline for the Management of Gout. A 57-item questionnaire was administered to a sample of US rheumatologists. Stated adherence scores were based on several guideline recommendations reported to be followed by rheumatologists in practice, whereas stated agreement scores were based on whether respondents always followed the recommendations. All 201 rheumatologists approached completed the questionnaire. The mean overall stated adherence score was 11.5 (maximum 15), whereas the mean overall stated agreement score was 7.7 (maximum 14). Less experienced rheumatologists (≤ 8 yrs; n = 49) were likely to claim adherence to more individual ACR recommendations than those with more experience (> 8 yrs; n = 152; mean stated adherence score: 12.3 vs 11.3; P ≤ 0.05). Rheumatologists who claimed to see ≤ 75 patients with gout in 6 months (n = 66) had a mean stated adherence score of 12.1 vs 11.2 for those who claimed to have seen > 75 patients (P ≤ 0.05). Approximately 78% of rheumatologists claimed to follow the guideline for initiating urate-lowering therapy (ULT), and 89% were likely to prescribe allopurinol as a first-line ULT. Claimed adherence to recommendations for dosing was lower (febuxostat: 43%; allopurinol: 39%). Rheumatologists from academic settings were more likely to prescribe an interleukin-1 inhibitor for gout flares. The self-reported practice of the surveyed US rheumatologists was generally concordant with the 2020 ACR Guideline for the Management of Gout. However, there were gaps in guideline knowledge and stated adherence among rheumatologists, mainly concerning the dosing of treatment regimens.

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.

Are gout patients with negative dual-energy computed tomography for monosodium urate crystal deposition easy to treat?

Abstract Objectives To determine the clinical associations and predictive value of two thresholds of negative dual-energy CT (DECT) for MSU crystal deposition in gout patients initiating urate-lowering therapy (ULT) and identify which threshold is more clinically relevant. Methods Patients from the CRYSTALILLE cohort with a diagnosis of gout naïve to ULT with baseline DECT scans of the knees and feet were selected. Two thresholds of positivity for DECT detection of MSU crystal deposition were considered (&amp;lt;0.01 cm3 and &amp;lt;0.1 cm3). Baseline characteristics and the prediction of key outcomes after ULT initiation, including reaching serum urate (SU) levels &amp;lt;6.0 and 5.0 mg/dl and occurrence of flares at 6, 12 and 24 months, associated with both thresholds of negative DECTs were compared with those of patients having positive DECT scans. Results A total of 211 patients, median age 66.2 years [interquartile range (IQR) 57–75.8], with a median symptom duration of 3 years (IQR 0–7.8) were included. A total of 38/211 (18%) and 90/211 (43%) had negative DECT scans for the 0.01 and 0.1 cm3 thresholds, respectively. Factors associated with negative DECT scans were younger age, shorter symptom duration and an absence of cardiovascular disease for both volume thresholds. A total of 9/39 (23.1%), 3/26 (11.5%) and 1/18 (5.6%) patients with &amp;lt;0.1 cm3 MSU crystals had flares at 6, 12 and 24 months, respectively, compared with 18/45 (40.0%), 9/36 (25.0%) and 2/18 (11.1%) patients with ≥0.1 cm3 (P &amp;gt; 0.05). Overall, 95 patients (68.3%) reached SU levels &amp;lt;6.0 mg/dl and 68 (48.9%) reached levels &amp;lt;5.0 mg/dl, without any difference between positive and negative DECTs, with ULT dosages that tended to be lower in patients with negative DECTs. Conclusion The 0.1 cm3 threshold was better correlated with clinical presentation and evolution than the 0.01 cm3 threshold. Gout patients with negative DECTs exhibit milder disease and a lower comorbidity burden. They do not exhibit particularly easy-to-treat hyperuricaemia but they may have a lower risk of flares.

Cohort study investigating gout flares and management in UK general practice

BackgroundGout is the most common inflammatory arthritis and is almost exclusively managed in primary care, however the course and severity of the condition is variable and poorly characterised. This research aims improve understanding about the frequency of, and factors associated with, gout flares in the UK and characterise the factors associated with the initiation of ULT.MethodsUsing the Clinical Practice Research Database, patients with a coded incident gout diagnosis without a prior prescription for urate-lowering therapy (ULT) were identified. Gout flares post diagnosis and ULT initiation were identified through prescribing and coded data. Patient characteristics, co-morbidities and co-prescribing were co-variants. Factors associated with gout flares and ULT initiation were analysed using cox-proportional hazard model and logistic regression.ResultsFifty-one thousand seven hundred eighty-four patients were identified: 18,605 (35.9%, 95%CI 35.5–36.3%) had experienced ≥ 1 recurrent flare, 17.4% (95%CI 17.1–17.8%) within 12 months of diagnosis. Male sex, black ethnicity, higher BMI, heart failure, CKD, CVD and diuretic use were associated with flares, with the highest HR seen with high serum urate levels (≥ 540 µmol/L HR 4.63, 95%CI 4.03–5.31). ULT initiation was associated with similar variables, although higher alcohol intake and older age were associated with lower odds of ULT initiation but were not associated with flares. ULT was initiated in 27.7% (95%CI 27.3–28.0%): 5.7% (95%CI 5.5–5.9%) within 12 months of diagnosis. ULT initiation rates were higher in patients with recurrent flares.ConclusionApproximately one in six people with incident gout had a second flare within 12 months. Factors associated with flare recurrence and ULT initiation were similar, but ULT initiation occurred later after diagnosis than previously thought.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

Colchicine for cardiovacular risk reduction in lower extremity peripheral artery disease

Abstract Introduction Although recent evidence from randomized trials suggests colchicine can reduce major adverse cardiovascular events (MACE) in patients with coronary artery disease, its effect in lower extremity peripheral artery disease (PAD) is not known.1,2 To make inferences about the effects of colchicine in PAD, we leveraged the variable prescribing practice of adding colchicine versus a non-steroidal anti-inflammatory (NSAID) to urate lowering therapy in patients with gout and PAD. Purpose Estimate the effect of colchicine therapy initiation on adverse cardiovascular and limb events in a real-world sample of high-risk patients with PAD and gout. Methods A pragmatic open-label target trial comparing colchicine initiators (treatment group) to NSAID initiators (control group) was emulated in PAD patients taking either drug in conjunction with initiation of urate lowering therapy. Patients were enrolled between July 2007 and December 2019 using electronic health records from a multi-hospital academic medical system linked to Medicare claims data. Patients with contraindications to colchicine or NSAIDs (e.g., severe kidney disease, hepatic failure) were excluded. Inverse probability of treatment weighting was used to create a pseudopopulation balanced with respect to risk factors for the outcomes. The primary outcome was a 5-year composite of major adverse limb events (MALE), MACE, and all-cause mortality. Secondary outcomes included MALE and death, MACE and death, and individual components of the primary outcome accounting for the competing event of death. Risks were estimated with the Kaplan-Meier estimator for the composite outcomes and the Aalen-Johansen estimator for the competing event outcomes. Percentile based 95% confidence intervals were generated using nonparametric bootstrapping. Results A total of 1,786 patients were enrolled; mean age was 77 years (SD 7), 33% were female, and 9% were non-white race (Table). Maximum absolute standardized mean difference in relevant covariates was 23% prior to weighting and 0.8% after weighting, indicating covariate balance. The risk of the primary composite outcome of MALE, MACE, and death at 5 years was 58% (95% CI 55%, 61%) in the colchicine group and 60% (95% CI 56%, 64%) in the control group, with a risk difference of -2% (-8%, 4%) and risk ratio of 0.96 (0.89, 1.04; Figure). Similar findings were noted in the secondary composite outcomes (Figure). In the analysis accounting for the competing risk of death, the cause-specific risk of MALE (9% colchicine vs. 9% control) and MACE (24% colchicine vs. 26% control) alone were similar at 5 years. Conclusions In a real-world sample of high-risk patients with PAD and gout, colchicine did not appear to reduce the risk of adverse cardiovascular or limb events. The cardiovascular benefits of colchicine in older populations with PAD and advanced systematic atherosclerosis remain uncertain.Table.Patient characteristics.Figure.Weighted Kaplan-Meier estimates.

Implementing treat-to-target urate-lowering therapy during hospitalizations for gout flares

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

Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink

ObjectivesTo determine the risk of adverse events associated with colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis when initiating allopurinol for gout.MethodsWe conducted two matched retrospective cohort studies in linked UK...

Efficacy and safety of tart cherry supplementary citrate mixture on gout patients: a prospective, randomized, controlled study

BackgroundLow urine pH, which may be mediated by metabolic syndrome (MetS), is common in gout. Tart cherries are shown to improve MetS symptoms and possess anti-inflammatory properties. However, the efficacy of tart cherry supplements on urine pH has yet to be studied.ObjectivesThis study aimed to investigate the efficacy and safety of tart cherry supplementary citrate (TaCCi) mixture on urine pH, serum urate (sUA), C-reactive protein (CRP), and gout flares in gout patients initiating urate-lowering therapy (ULT), in comparison to citrate mixture and sodium bicarbonate.MethodsA prospective, randomized (1:1:1), open-label, parallel-controlled trial was conducted among 282 men with gout and fasting urine pH ≤ 6, who were initiating ULT with febuxostat (initially 20 mg daily, escalating to 40 mg daily if serum urate ≥ 360 μmol/L). Participants were randomized to groups taking either sodium bicarbonate, citrate mixture, or TaCCi mixture. All participants were followed every 4 weeks until week 12. Urine pH and sUA were co-primary outcomes, with various biochemical and clinical secondary endpoints.ResultsUrine pH increased to a similar extent in all three groups. SUA levels declined in all three groups as well, with no significant differences observed between the groups. At week 12, the TaCCi mixture group exhibited a greater reduction in the urine albumin/creatinine ratio (UACR) compared to the other two groups (p < 0.05). Participants taking TaCCi mixture or citrate mixture experienced fewer gout flares than those in the sodium bicarbonate group over the study period (p < 0.05). Additionally, the TaCCi mixture group had a lower CRP level at week 12 relative to the other two groups (p < 0.01). Adverse events were similar across all three groups.ConclusionThe TaCCi mixture had similar efficacy and safety on urine alkalization and sUA-lowering as the citrate mixture and sodium bicarbonate in patients with gout. However, the TaCCi mixture resulted in greater improvements in UACR and CRP, which suggests that tart cherry supplements may provide additional benefits for renal protection and reduce inflammation in gout, particularly when starting ULT.Trial registrationThis project was registered in ChiCTR (www.chictr.org.cn), with the registration number: ChiCTR2100050749.

The Effect of Decrease in Serum Urate for the Risk of Gout Flares During Urate-Lowering Therapy Initiation Among Chinese Male Gout Patients: A Prospective Cohort Study.

Higher baseline serum urate or higher initial urate-lowering medication dose increased risk of gout flares during urate-lowering therapy (ULT) initiation. The decrease in serum urate may play a crucial role in this process. Therefore, we aim to explore the relationship between decrease in serum urate and the risk of gout flares during ULT initiation. A 12-week prospective cohort study of Chinese male gout patients was conducted at Shandong Provincial Clinical Research Center for Immune Diseases and Gout in China. Patients were grouped by baseline serum urate (7-7.9 mg/dL, 8-8.9 mg/dL and ≥9 mg/dL). All patients received febuxostat 20 mg daily during weeks 0-4, then escalated to 40mg during weeks 4-12 if serum urate >6mg/dL. The main outcomes were the number of gout flares and the decrease in serum urate. Poisson regression was performed. A total of 282 participants were enrolled, of whom 260 completed (84, 87 and 89 in each group) from March 2021 to December 2021. A 44.2% of all participants experienced at least one gout flare. In the multivariate Poisson regression 1, Δ serum urate 0-12 weeks (IRR 1.184, 95% CI, 1.062-1.320; P=0.002), the number of gout flares before treatment 1 year (1.017, 1.010-1.024; P<0.001) and tophus (1.580, 1.023-2.440; P=0.039) were independently associated with the number of gout flares. While in the multivariate Poisson regression 2, baseline serum urate (1.256, 1.050-1.503; P=0.013) and the number of gout flares before treatment 1 year (1.014, 1.007-1.022; P<0.001) were independently associated with the number of gout flares, Δ serum urate 0-12 weeks (1.055, 0.923-1.207; P=0.433) was no longer a risk factor. ULT-induced gout flares depend on the degree of decrease in serum urate, which is affected by baseline serum urate. Higher baseline serum urate and greater decrease in serum urate lead to higher risk of gout flares.

Serum Urate Monitoring Among Older Adults With Gout: Initiating Urate-Lowering Therapy in Ontario, Canada.

To assess the proportion of, and factors associated with, older adults with gout receiving a serum urate (SUA) test after starting urate-lowering therapy (ULT). We performed a population-based retrospective cohort study in Ontario, Canada in patients ages ≥66 years with gout, newly dispensed ULT between 2010 and 2019. We characterized patients with SUA testing within 6 and 12 months after ULT dispensation. Multilevel logistic regression clustered by ULT prescriber evaluated the factors associated with SUA monitoring within 6 months. We included 44,438 patients with a mean ± SD age of 76.0 ± 7.3 years and 64.4% male. Family physicians prescribed 79.1% of all ULTs. SUA testing was lowest in 2010 (56.4% at 6 months) and rose over time to 71.3% in 2019 (P < 0.0001). Compared with rheumatologists, family physicians (odds ratio [OR] 0.26 [95% confidence interval (95% CI) 0.23-0.29]), internists (OR 0.34 [95% CI 0.29-0.39]), nephrologists (OR 0.37 [95% CI 0.30-0.45]), and other specialties (OR 0.25 [95% CI 0.21-0.29]) were less likely to test SUA, as were male physicians (OR 0.87 [95% CI 0.83-0.91]). Patient factors associated with lower odds of SUA monitoring included rural residence (OR 0.81 [95% CI 0.77-0.86]), lower socioeconomic status (OR 0.91 [95% CI 0.85-0.97]), and patient comorbidities. Chronic kidney disease, hypertension, diabetes mellitus, and coprescription of colchicine/oral corticosteroids (OR 1.31 [95% CI 1.23-1.40]) were correlated with increased SUA testing. SUA testing is suboptimal among older adults with gout initiating ULT but is improving over time. ULT prescriber, patient, and prescription characteristics were correlated with SUA testing.

La gota preclínica es frecuente en el paciente con enfermedad renal crónica estadio 3-5. Relevancia de la ecografía articular

BackgroundOne in 10 patients with hyperuricemia may develop gout over time, with urate deposition sometimes asymptomatic. Recent reviews and guidelines support ultrasound (US) to assess asymptomatic hyperuricemic (AH) patients to detect gout lesions, showing double contour (DC) and tophus the highest specificities and positive predictive values. Hyperuricemia and gout are common in chronic kidney disease (CKD), especially with glomerular filtration rate (GFR) <60, and both are associated with worse prognosis, although treatment of AH in CKD is not yet recommended in all guidelines. US gout lesions have been found more frequently in AH (up to 35%) than in normouricemic (NU) patients, but evidence is scarce in CKD. ObjectivesTo assess the prevalence of urate deposit in stages 3–5 CKD detected by US, and to investigate if there are differences between AH and NU patients. MethodsMulticenter cross-sectional study, recruiting patients aged ≥18 years with AH and stages 3–5 CKD in four hospitals. A comparator group of NU patients with stages 3–5 CKD was included. Exclusion criteria: previous diagnosis of gout, tophi. Hyperuricemia was defined as serum uric acid (sUA) >7 mg/dl, documented at least twice during the last 12 months. A standardized US exam of the knees and bilateral first metatarsophalangeal joints was performed to assess patients for DC/tophus as defined by OMERACT. Demographic, clinical and laboratory data were recorded. A descriptive analysis was performed using SPSS. Pre-clinical gout (PCG: DC and/or tophus) was considered as outcome variable. Chi-square and Fisher's exact test were used for qualitative variables, and Mann–Whitney U test for quantitative variables; significant threshold p<0.05. ResultsFifty-three patients with stages 3–5 CKD (59.6% stage 3, 19.1% stage 4, 21.3% stage 5) were recruited, 38 AH (71.7%) and 15 NU. A higher prevalence of US findings was observed in HU patients compared to NU patients (DC 23.7% vs. 13.3%, tophus 31.6% vs. 26.7%, PCG 39.5% vs. 33.3%), although the differences were not statistically significant. NU patients had CKD of longer duration than HU patients [11 (7.2–13.5) vs. 6 (2–9.2) years; p = 0.02], with no differences in sex, age, comorbidities, or urate-lowering therapy (ULT) (66.7% vs. 44.7%; p = 0.05) and other treatments. Seventy percent of NU patients with TRU had AH before starting treatment. In patients with tophi, we observed a trend towards shorter duration of CKD and shorter duration of treatment with ULT compared to those without tophi [3.5 (2–6.7) vs. 7 (3–12) years; p = 0.05] and [22 (12–44) vs. 39 (29–73) months; p = 0.08], respectively. This trend was also observed in PCG, but not in DC, first US sign to disappear after initiation of ULT. Ninety percent of patients (100% in non-dialyzed patients) with PCG had a median uricemia ≥5 mg/dl in the past 12 months. ConclusionWe found a significant prevalence of asymptomatic urate deposition in patients with stages 3–5 CKD, mostly in subjects with median uricemia ≥5 mg/dl in the last 12 months. Early diagnosis of PCG by musculoskeletal US in CKD may allow earlier introduction and optimization of ULT. This will probably contribute to slowing down the progression of this pathology, which makes it essential to promote collaboration between Nephrology and Rheumatology.