Psychometric evaluation of the Adherence to Refills and Medications Scale (ARMS) in Australians living with gout.

This study aimed to examine psychometric properties of the Adherence to Refills and Medications Scale (ARMS) in people with gout. We conducted exploratory factor analysis (EFA) and tested internal consistency (ordinal and Cronbach's alpha coefficients) and agreement (intraclass correlation coefficient (2,1)) in ARMS scores across three timepoints (baseline, 6, and 12 months) in 487 people with gout. The Kruskal-Wallis test, Spearman's rank, Kendall's tau-b correlations, and logistic regression were used to examine the criterion-related validity of the ARMS and factors associated with the ARMS. EFA suggested a one-factor structure, explaining 43.2% of total variance. High internal consistency (ordinal alpha = 0.902 at baseline) and moderate agreement in ARMS scores over time (ICCs > 0.5; p < 0.001) were observed. Lower ARMS scores (indicating better adherence) predicted achieving target serum urate (OR, 0.89; 95% CI, 0.83-0.95; p < 0.001), but not urate-lowering therapy (ULT) adherence (Proportion of Days Covered (PDC) ≥ 80%) (OR, 0.93; 95% CI, 0.81-1.05; p = 0.261). Negative correlations between ARMS and PDC were not statistically significant (Kendall's tau-b, r = - 0.126, p = 0.078; Spearman's rho = - 0.173, p < 0.073). Differences in median ARMS scores (IQR) of 16 (14-20), 13 (12-15), and 17.5 (15-21) in three groups of participants who reported (1) not taking ULT, (2) taking ULT and adherent, and (3) taking ULT but not adherent, respectively, were statistically significant (p < 0.001). Age was the only patient factor independently associated with optimal adherence (ARMS score = 12) (OR, 1.91; 95% CI, 1.50-2.43; p < 0.001). The ARMS is a reliable and valid measure of medication adherence behaviours in people with gout, justifying its use in gout medication adherence research.

Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial.

RATIONALE & OBJECTIVE: We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). STUDY DESIGN: Prespecified sub cohort analysis of a randomized controlled trial. SETTING: & Participants: A sub study of the STOP Gout trial in participants with CKD. CKD was defined as an eGFR 30-59 mL/min/1.73 m2 at baseline. EXPOSURE: Trial participants with CKD and gout and serum urate (sUA) concentration ≥6.8 mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal sUA of <6.0 mg/dl (<5.0 mg/dl with tophi) (Phase 1) and maintained during weeks 25-48 (Phase 2). Gout flare was assessed between weeks 49-72 (Phase 3). OUTCOME: Gout flare between weeks 49-72 (Phase 3) was the primary outcome. Secondary outcomes included sUA goal achievement and ULT dosing at end of Phase 2, and serious adverse events (SAEs). ANALYTICAL APPROACH: Outcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm. RESULTS: 351 of 940 participants (37.3%) had CKD; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; p=0.02) despite similar attainment of sUA goal (79% vs. 81%; p=0.6) by the end of Phase 2. Acute kidney injury (AKI) was more common in participants with stage 3 CKD randomized to allopurinol compared to febuxostat. LIMITATIONS: Limited power to assess infrequent safety events, largely male, older population. CONCLUSIONS: Allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen.

Urate-lowering therapy in patients with hyperuricemia and heart failure: A retrospective cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: Elevated serum uric acid (sUA) is associated with heart failure (HF). HYPOTHESIS: Urate-lowering therapy (ULT) in HF is associated with lower risk of HF hospitalization (hHF) and mortality. METHODS: Data on patients with HF and gout or hyperuricemia in the Clinical Practice Research Datalink database linked to the Hospital Episode Statistics and the Office for National Statistics in the United Kingdom were analyzed. Risks of hHF and all-cause mortality or cardiovascular-related mortality by ULT exposure (ULT initiated within ≤6 months of gout or hyperuricemia diagnosis) were analyzed in a propensity score-matched cohort using adjusted Cox proportional hazards regression models. RESULTS: Of 2174 propensity score-matched pairs, patients were predominantly male, aged >70 years, with mean ± standard deviation sUA 9.3 ± 1.8 (ULT-exposed) and 9.4 ± 1.9 mg/dL (ULT-unexposed). At 5 years, ULT-exposed patients had a 43% lower risk of hHF or all-cause mortality (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.51-0.65) and a 19% lower risk of hHF or cardiovascular-related mortality (adjusted HR: 0.81; 95% CI: 0.71-0.92) versus no ULT exposure. CONCLUSION: ULT was associated with reduced risk of adverse clinical outcomes in patients with HF and gout or hyperuricemia over 5 years.

Predictors of Inadequate Serum Urate Response to Low-Dose Febuxostat in Male Patients with Gout.

Objective: This study aimed to understand predictors of inadequate response (IR) to low-dose febuxostat treatment based on clinical variables. Methods: We pooled data from 340 patients of an observational cohort and two clinical trials who received febuxostat 20 mg/day for at least 3 months. IR was defined as failure to reach the target serum urate level (sUA<6 mg/dL) at any time point during 3 months treatment. The potential predictors associated with short- or mid-term febuxostat IR after pooling the three cohorts were explored using mixed-effect logistic analysis. Machine learning models were performed to evaluate the predictors for IR using the pooled data as the discovery set and validated in an external test set. Results: Of the 340 patients, 68.9% and 51.8% were non-responders to low-dose febuxostat during short- and mid-term follow-up, respectively. Serum urate and triglyceride (TG) levels were significantly associated with febuxostat IR, but were also selected as significant features by LASSO analysis combined with age, BMI, and C-reactive protein (CRP). These five features in combination, using the best-performing stochastic gradient descent classifier, achieved an area under the receiver operating characteristic curve of 0.873 (95% CI [0.763, 0.942]) and 0.706 (95% CI [0.636, 0.727]) in the internal and external test sets, respectively, to predict febuxostat IR. Conclusion: Response to low-dose febuxostat is associated with early sUA improvement in individual patients, as well as patient age, BMI, and levels of TG and CRP.

Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study.

OBJECTIVES: Colchicine is commonly used to prevent flares when starting urate-lowering therapy for gout. Patients with gout are frequently concurrently prescribed other medications (such as statins) that may interact with colchicine, increasing the risk of adverse events. The aim of this study was to describe potential prognostic factors for adverse events in patients prescribed colchicine when initiating allopurinol. METHODS: We conducted a retrospective cohort study in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with colchicine (01/04/1997-30/11/2016) were included. Potential prognostic factors were defined, and the likelihood of adverse events, including diarrhoea, nausea or vomiting, myocardial infarction (MI), neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression, were estimated. RESULTS: From 01/04/1997-30/11/2016, 13 945 people with gout initiated allopurinol with colchicine prophylaxis (mean age 63.9 (SD 14.7) years, 78.2% male). One quarter (26%, 95% CI 25% to 27%) were prescribed ≥1 potentially interacting medicines, most commonly statins (21%, 95% CI 20% to 22%). Statins were not associated with increased adverse events, although other drugs were associated with some adverse outcomes. Diarrhoea and MI were associated with more comorbidities and more severe CKD. CONCLUSION: People were given colchicine prophylaxis despite commonly having preexisting prescriptions for medications with potential to interact with colchicine. Adverse events were more common in people who had more comorbidities and certain potentially interacting medications. Our findings will provide much-needed information about prognostic factors for colchicine-related adverse events that can inform treatment decisions about prophylaxis when initiating allopurinol.

Health literacy and gout characteristics in a primary care cohort.

Objectives: To examine the cross-sectional association between health literacy and gout characteristics. Methods: In a primary care cohort of adults living with gout, the prevalence of poor health literacy was defined using the Single-Item Literacy Screener (SILS). Multiple logistic regression was used to obtain adjusted odds ratios (ORs) for the cross-sectional associations between health literacy and individual gout characteristics (frequency of flares, age at gout onset, history of oligo-/polyarticular flares, allopurinol use, allopurinol dose and serum urate level) with 95% CIs and adjustment for age, sex, deprivation and further education. Results: Of 551 participants [mean age 54.4 years (s.d. 11.2), 498 (90.4%) male], 163 (30.1%) reported two or more flares in the previous 12 months. Fifty-one (9.4%) had poor health literacy. Poor health literacy was associated with having two or more flares in the preceding 12 months [adjusted OR 4.10 (95% CI 2.04, 8.19)] and a history of oligo-/polyarticular flares [OR 1.93 (95% CI 1.06, 3.55)]. No associations were identified between health literacy and age at gout onset [OR 0.99 (95% CI 0.96, 1.01)], allopurinol use [OR 0.88 (95% CI 0.46, 1.65)] or dose [OR 1.00 OR (95% CI 1.00, 1.00)] or serum urate [most recent serum urate OR 1.0 (95% CI 1.00, 1.00)]. Conclusions: Frequent flares and a history of oligo-/polyarticular flares were associated with poor health literacy. Since health literacy is an important determinant of health outcomes, it is important to consider health literacy when providing information and education to people with gout.

Urate-lowering agents do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout: a prospective open-label cohort study.

OBJECTIVE: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting. METHODS: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18-45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3. RESULTS: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9-54.3] vs 48.4%, [27.4-67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6-69.92] vs 58.5 M/mL, [49.8-116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well. CONCLUSION: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout.

Estimation of adherence to urate-lowering therapy in people living with gout using Australia's Pharmaceutical Benefits Scheme and patient-reported dosing.

AIMS: The aim of this study was to estimate adherence to urate-lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient-reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day). METHODS: Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12-month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%. We measured the correlation between the two methods of calculating PDC using a Wilcoxon signed rank test. Agreement between ULT-taking status (self-reports) and ULT-dispensed status (PBS records) was tested with Cohen's kappa (κ), and positive and negative percent agreement. RESULTS: Allopurinol was prescribed in 93.5% of participants taking ULT. Their self-reported mean daily dose (SD) was 291 (167) mg/day. Mean PDC (SD) for allopurinol was 83% (21%) calculated using self-reported dose, and 63% (24%) using WHO's DDD. Sixty-three percent of allopurinol users were identified as adherent (PDC ≥80%) using self-reported dose. There was good agreement between self-reported ULT use and PBS dispensing claims (κ = 0.708, P < .001; positive percent agreement = 90%, negative percent agreement = 82%). CONCLUSIONS: Participant-reported allopurinol daily doses, in addition to PBS dispensing claims, may enhance confidence in estimating PDC and adherence compared to using DDD. This approach improves adherence estimations from pharmaceutical claims datasets for medications where daily doses vary between individuals or where there is a wide therapeutic dose range.

Hyperuricemia: An Intriguing Connection to Metabolic Syndrome, Diabetes, Kidney Disease, and Hypertension.

PURPOSE OF THE REVIEW: Our review explores the epidemiology, physiology, and clinical data surrounding the connection between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension. RECENT FINDINGS: Compelling physiologic mechanisms have been proposed to explain a causal relationship between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension but clinical studies have given mixed results in terms of whether intervening with hyperuricemia using urate-lowering therapy has any beneficial effects for patients with these conditions. Despite the large amount of research already put into this topic, more randomized placebo-controlled trials are needed to more firmly establish whether a cause-effect relationship exists and whether lowering uric acid levels in patients with these conditions is beneficial.

An updated systematic review and meta-analysis of randomised controlled trials on the effects of urate-lowering therapy initiation during a gout flare.

BACKGROUND: There is uncertainty about the optimal time to start urate-lowering therapy (ULT) in the setting of a gout flare. The aim was to perform a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the effects of ULT initiation during a gout flare. METHODS: This systematic review was conducted in accordance with PRISMA methodology. MEDLINE, EMBASE and The Cochrane Library were searched for studies published between database inception to 1 March 2023. RCTs published in English that examined ULT initiation during a gout flare in adults ≥18 years were included. The quality of included studies was assessed using the revised Cochrane Risk of Bias tool 2.0. Data were extracted for the following outcomes: patient-rated pain score, duration of gout flare, recurrent gout flares, time to achieve target serum urate, adherence to ULT, patient satisfaction with treatment and adverse events. Meta-analyses were performed using Review Manager v5.4. This study is registered on PROSPERO, number CRD42023404680. RESULTS: A total of 972 studies were identified and of these, six RCTs met the criteria for inclusion in the analysis. Three studies were assessed as having high risk of bias, one study as having some concerns, and two studies as having low risk of bias. In total, there were 445 pooled participants; 226 participants randomised to early initiation of ULT and 219 to placebo or delayed initiation of ULT. Allopurinol was used in three studies, febuxostat in two studies and probenecid in one study. Few participants (n = 62, 13.9 %) had tophaceous gout. Participants with renal impairment were excluded from most studies. There were no differences in patient-rated pain scores at baseline, days 3-4, days 7-8, day 10 or days 14-15 (p ≥ 0.42). Additionally, there was no significant difference in time to resolution of gout flare (standardised mean difference 0.77 days; 95 % CI -0.26 to 1.79; p = 0.14) or the risk of recurrent gout flare in the subsequent 28 to 30 days (RR 1.06; 95 % CI 0.59 to 1.92; p = 0.84). Adverse events were similar between groups. The included studies did not report time to achieve target serum urate, long-term adherence to ULT, or patient satisfaction with treatment. CONCLUSION: There appears to be no evidence for harm or for benefit to initiating ULT during a gout flare. These findings have limited applicability to patients with tophaceous gout, or those with renal impairment.

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

OBJECTIVES: To evaluate a strategy designed to optimise care and increase uptake of urate-lowering therapy (ULT) during hospitalisations 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-hospitalisation rates, were compared between patients hospitalised for flares in the 12 months post-implementation and 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 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% confidence interval (CI) 4.36-30.5; p < 0.001). After implementation, more patients achieved a serum urate ≤360 micromol/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-hospitalised for flares was 14.9% pre-implementation vs. 9.3% post-implementation (aOR 0.53, 95% CI 0.22 to 1.32; p = 0.18). CONCLUSION: Over 90% of patients were initiated on ULT after implementing a strategy to optimise hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalisations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalised gout patients to achieve urate targets, closer primary-secondary care integration is still needed.

Cohort study investigating gout flares and management in UK general practice.

BACKGROUND: Gout 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. METHODS: Using 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. RESULTS: Fifty-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. CONCLUSION: Approximately 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.

Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

The nurse's role in managing gout in the modern era: A systematic review of the literature.

The current treatment of gout is largely suboptimal, with up to 89% of hospitalizations being preventable due to inadequate care. The present study performed a systematic review in an aim to identify barriers to optimal gout treatment (Q1), understand how frequently nurses are involved in the management of gout (Q2), and examine the role of the nurse in the management of gout (Q3). A systematic review was performed, focusing on studies reporting on the nurse's role in the management of gout and the quality of the gathered items was appraised based on the risk of bias. In total, 15 records fulfilled the eligibility criteria and were used in the present systematic review. The main barriers were attributed to the patient's experiences with gout and lay beliefs, which affected seeking advice and adherence to treatment (Q1). Recently, however, several advances in patient care, including nurse-led clinics, have expanded the nurse's role, accounting for as much as 26% of the annual visits (Q2). Nurse-led interventions, such as education and lifestyle counseling, increased adherence to treatment (Q3). On the whole, nurses are key players in multidisciplinary teams and should be capable of engaging in shared decision-making processes, goal setting, providing patients with education and information, and making appropriate referrals.

Association between the initial dose urate-lowering drugs and gout flares in adult males with gout.

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

Serum uric acid levels in kidney transplant recipients: A cause for concern? A review of recent literature.

The impact of elevated serum uric acid levels i.e., hyperuricemia, on native and transplant chronic kidney disease progression has been debated. This literature review presents an analysis of multiple studies exploring the relationship between serum uric acid levels and kidney transplant outcomes. The review includes a summary of the pathophysiology of hyperuricemia and gout, a review of urate-lowering therapies, and an appraisal of multiple studies examining the association or lack thereof between serum uric acid level and kidney transplant outcomes. Based on these studies, elevated serum uric acid levels may contribute to CKD progression in kidney transplant recipients. In this review, we also summarize current literature to highlight risk factors associated with hyperuricemia as well as the need for further investigation to monitor and manage hyperuricemia in kidney transplant recipients.

The Impact of Label Changes (Boxed Warning) on Real-World Febuxostat Utilization in Patients with Gout: A Cross-Sectional Drug Utilization Study.

INTRODUCTION: This drug utilization study evaluated the impact of 2019 label changes on real-world febuxostat utilization among patients with gout. We describe the numbers and proportions of patients initiating febuxostat as new users (allopurinol-naïve) or prevalent new users (prior allopurinol use) and data on febuxostat users with established cardiovascular disease (CVD) morbidities before, during, and after the 2019 label changes. METHODS: This descriptive, non-interventional, cross-sectional study used data from two large administrative claims databases in the United States, the IQVIA PharMetrics Plus database and the Optum Research Database (ORD). The study population included patients with gout initiating febuxostat on or after June 1, 2016. Data were collected on febuxostat and allopurinol use, established CVD morbidities, comorbidities of interest, concomitant medications, and patient demographics. RESULTS: In both databases, the total number of febuxostat users and proportion of patients who initiated febuxostat as new users both decreased during the study period. Of 13,848 patients in the PharMetrics Plus cohort, 42.7% were new users of febuxostat and 57.3% were prevalent new users. In the ORD cohort, 40.5% of the 10,198 patients were new users and 59.5% were prevalent new users. The most common established CVD morbidities in the 12 months prior to initiation of febuxostat were diabetes mellitus, ischemic heart disease, and heart failure/cardiomyopathy. CONCLUSIONS: Although the benefit-risk profile for febuxostat is considered favorable for the treatment of hyperuricemia in certain patients with gout, real-world febuxostat utilization decreased during the study period, presumably in response to the label change.

Gout Remission as a Goal of Urate-Lowering Therapy: A Critical Review.

Urate-lowering therapies for the management of gout lead to a reduction in serum urate levels, monosodium urate crystal deposition, and the clinical features of gout, including painful and disabling gout flares, chronic gouty arthritis, and tophi. Thus, disease remission is a potential goal of urate-lowering therapy. In 2016, preliminary gout remission criteria were developed by a large group of rheumatologists and researchers with expertise in gout. The preliminary gout remission criteria were defined as: serum urate < 0.36 mmol/L (6 mg/dL); an absence of gout flares; an absence of tophi; pain due to gout < 2 on a 0-10 scale; and a patient global assessment < 2 on a 0-10 scale over a 12-month period. In this critical review, we describe the development of the preliminary gout remission criteria, the properties of the preliminary gout remission criteria, and clinical studies of gout remission in people taking urate-lowering therapy. We also describe a future research agenda for gout remission.

Efficacy of initiating urate-lowering therapy during an acute gout episode: a meta-analysis.

OBJECTIVE: This study aimed to evaluate the effectiveness of initiating urate-lowering therapy (ULT) during acute gout episodes. METHODS: We performed a literature search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (from inception to February 2023). We conducted a comprehensive review and meta-analysis of randomized controlled trials (RCTs) that examined the efficacy of ULT in individuals with acute gout flares. RESULTS: This review included six RCTs with 479 patients (225 experimental participants and 254 controls). The experimental group had longer days to resolution than did the control group. There was no significant difference in the pain visual analogue scale score between the groups by day 10. Erythrocyte sedimentation rate and C­reactive protein level did not significantly differ between the groups by days 7 to 14. Both groups had similar rates of recurrent gout attacks by 30 days. There was no significant between-group difference in the dropout rate. CONCLUSION: Initiating ULT therapy during a gout attack does not appear to increase the duration of the flare or aggravate pain. Despite these findings, further studies with larger sample sizes are necessary to support these conclusions.