Use Of Allopurinol Research Articles

Health-related quality of life by gout severity in women and men with gout in primary care: results from a questionnaire study in Western Sweden

Objective We aimed to compare health-related quality of life (HRQoL) by gout severity, overall and by sex. Method A questionnaire was sent to patients with gout (n = 1444) identified at 12 primary care centres in Western Sweden. The questionnaire asked about comorbidities, gout-specific aspects, and HRQoL, using the RAND 36-Item Health Survey. Responders were divided into ‘mild’, ‘moderate’, or ‘severe’ gout based on the number of self-reported flares (0, 1–2, ≥ 3) during the past 12 months. Results Out of 1444 gout patients, 784 (54.3%) responded to the questionnaire. Among the respondents, 673 [560 (83.2%) men and 113 (16.8%) women] provided answers regarding the number of gout flares in the past year. Of these, 322 (47.8%), 218 (32.4%), and 133 (19.8%) were classified as having mild, moderate, and severe gout, respectively. Allopurinol use was more frequent in those with mild disease. In more severe gout, HRQoL was reduced compared to less severe gout [severe vs mild gout, mean values for physical component summary (PCS) score 39.5 vs 43.6, p = 0.002, and mental component summary (MCS) score 46.6 vs 51.1, p < 0.001]. When excluding those with a flare in the past month, the HRQoL was still worse in severe gout (vs mild), although differences were attenuated and not statistically significant for the PCS and for women. Conclusion Gout severity, defined as the number of flares during the past year, was associated with significant reductions in HRQoL.

Cost-effectiveness of HLA-B*58:01 testing to prevent Stevens-Johnson syndrome/toxic epidermal necrolysis in Vietnam.

Background: HLA-B*58:01 is strongly associated with allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Vietnam. This study assessed the cost-effectiveness of this testing to prevent SJS/TEN. Methods: A model was developed to compare three strategies: no screening, use allopurinol; HLA-B*58:01 screening; and no screening, use probenecid. A willingness-to-pay of three-times gross domestic product per capita was used. Results: Compared with 'no screening, use allopurinol', 'screening' increased quality-adjusted life-years by 0.0069 with the incremental cost of Vietnam dong (VND)14,283,633 (US$617), yielding an incremental cost-effectiveness ratio of VND2,070,459,122 (US$89,398) per quality-adjusted life-year. Therefore, 'screening' was unlikely to be cost-effective under the current willingness-to-pay. Testing's cost-effectiveness may change with targeted high-risk patients, reimbursed febuxostat or lower probenecid prices. Conclusion: The implementation of nationwide HLAB*58:01 testing before the use of allopurinol is not cost-effective, according to this analysis. This may be due to the lack of quality data on the effectiveness of testing and costing data in the Vietnamese population.

Reno- and hepato-protective effect of allopurinol after renal ischemia/reperfusion injury: Crosstalk between xanthine oxidase and peroxisome proliferator-activated receptor gamma signaling.

Renal ischemia/reperfusion (I/R) is a common cause of acute kidney injury and remote liver damage is an ultimate negative outcome. Current treatments for renal I/R typically involve the use of antioxidants and anti-inflammatory to protect against oxidative stress and inflammation. Xanthine oxidase (XO) and PPAR-γ contribute to renal I/R-induced oxidative stress; however, the crosstalk between the two pathways remains unexplored. In the present study, we report that XO inhibitor, allopurinol (ALP), protects kidney and liver after renal I/R by PPAR-γ activation. Rats with renal I/R showed reduced kidney and liver functions, increased XO, and decreased PPAR-γ. ALP increased PPAR-γ expression and improved liver and kidney functions. ALP also reduced inflammation and nitrosative stress indicated by reduction in TNF-α, iNOS, nitric oxide (NO), and peroxynitrite formation. Interestingly, rats co-treated with PPAR-γ inhibitor, BADGE, and ALP showed diminished beneficial effect on renal and kidney functions, inflammation, and nitrosative stress. This data suggests that downregulation of PPAR-γ contributes to nitrosative stress and inflammation in renal I/R and the use of ALP reverses this effect by increasing PPAR-γ expression. In conclusion, this study highlights the potential therapeutic value of ALP and suggests targeting XO-PPAR-γ pathway as a promising strategy for preventing renal I/R injury.

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

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. 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. 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 12months prior to initiation of febuxostat were diabetes mellitus, ischemic heart disease, and heart failure/cardiomyopathy. 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.

The Effect of High-dose Allopurinol Pretreatment on Inflammatory Biomarkers and Post-revascularization Coronary Blood Flow in Non-STEMI Patients: A Randomized Double Blind Clinical Trial.

The use of allopurinol has shown promising outcomes in reducing oxidative processes responsible for atherogenic-related cardiovascular events. The current study aims to assess the effects of high-dose allopurinol on the post-revascularization coronary blood flow and inflammatory biomarkers in patients with non-ST segment elevated myocardial infarction (NSTEMI). Eighty NSTEMI patients were randomly divided into two groups: the intervention group (n=40), medicated with a high loading dose of 600 mg allopurinol before the coronary angiography, and the control group (n=40), treated with a placebo. The highly sensitive C-reactive protein (hs-CRP) was measured at baseline and within 24 hours after the cardiac interventions and compared between the case and control groups. Post percutaneous coronary intervention (PCI) Thrombolysis in Myocardial Infarction (TIMI) flow grading was also evaluated as a revascularization endpoint. The two groups of the study were similar in terms of demographic, clinical, laboratory, and angiographic characteristics (P-value>0.050). The assessed TIMI flow was similar between the cases and the controls both prior to (P-value=0.141) and after (P-value=0.395) the coronary angioplasty. The hs-CRP (P-value=0.016) was significantly higher in the control group. Post-angiographic assessment of hs-CRP revealed an insignificant difference between the groups (P-value=0.104). In conclusion, premedication with a high dose of allopurinol in NSTEMI patients did not affect the inflammatory biomarker or the revascularization endpoint.

Investigating the Anti-inflammatory Effect of Allopurinol on the Prevention of Prostate Cancer.

Introduction Gout is a form of arthritis that arises from the accumulation of uric acid in the bloodstream. Allopurinol, a medication that reduces uric acid levels, has also been shown to have anti-inflammatory effects. Research in this area seems to have mixed results. Furthermore, limited research has examined the relationship between gout treated with Allopurinol and its possible protective factors against prostate cancer. The purpose of this study was to examine the relationship between Allopurinol use and prostate cancer, controlling for demographic and metabolic factors. Methods Information was collected from the National Health and Nutrition Examination Survey (NHANES) dataset of theCenters for Disease Control and Prevention (CDC). Logistic regression analysis was employed to establish the correlation between the usage of Allopurinol and the occurrence of prostate cancer while considering variables such as weight, hypertension, hyperlipidemia, race, educational level, and marital status. The research received approval from the review board of the Physician's Journal of Medicine. Results We found no significant association between Allopurinol use and prostate cancer, controlling for covariates. Age was found to have a positive association with prostate cancer. Marriage was found to have a negative association with prostate cancer. Conclusion The results of this study did not find a significant association between Allopurinol use and the risk of prostate cancer. However, this study adds to the limited body of research examining the relationship between gout, Allopurinol, and prostate cancer and suggests that further research is needed in this area. Overall, while Allopurinol has been shown to have anti-inflammatory effects and is used to treat gout, its use does not appear to have a significant impact on the risk of developing prostate cancer.

The association of allopurinol with persistent physical disability and frailty in a large community based older cohort.

The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence-limiting physical disability at trial enrolment. This analysis examined the association of baseline and time-varying allopurinol use with persistent physical disability and new-onset frailty in participants with gout at baseline (self-report or use of any anti-gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional-hazards models were used for main analyses. This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow-up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23-0.92, p = 0.03). The strength of the association was modestly attenuated in the time-varying analysis (Adjusted HR 0.56, 0.29-1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62-1.12; FI: Adjusted HR 0.96, 0.74-1.24) or time-varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69-1.24; FI: Adjusted HR 1.02, 0.78-1.33). Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty.

Changes in Prescription Drug and Health Care Use Over 9 Years After the Large Drug Price Increase for Colchicine

Prescription drug prices are a leading concern among patients and policy makers. There have been large and sharp price increases for some drugs, but the long-term implications of large drug price increases remain poorly understood. To examine the association of the large 2010 price increase in colchicine, a common treatment for gout, with long-term changes in colchicine use, substitution with other drugs, and health care use. This retrospective cohort study examined MarketScan data from a longitudinal cohort of patients with gout with employer-sponsored insurance from 2007 through 2019. The US Food and Drug Administration's discontinuation of lower-priced versions of colchicine from the market in 2010. Mean price of colchicine; use of colchicine, allopurinol, and oral corticosteroids; and emergency department (ED) and rheumatology visits for gout in year 1 and over the first decade of the policy (through 2019) were calculated. Data were analyzed between November 16, 2021, and January 17, 2023. A total of 2 723 327 patient-year observations were examined from 2007 through 2019 (mean [SD] age of patients, 57.0 [13.8] years; 20.9% documented as female; 79.1% documented as male). The mean price per prescription of colchicine increased sharply from $11.25 (95% CI, $11.23-$11.28) in 2009 to $190.49 (95% CI, $190.07-$190.91) in 2011, a 15.9-fold increase, with the mean out-of-pocket price increasing 4.4-fold from $7.37 (95% CI, $7.37-$7.38) to $39.49 (95% CI, $39.42-$39.56). At the same time, colchicine use declined from 35.0 (95% CI, 34.6-35.5) to 27.3 (95% CI, 26.9-27.6) pills per patient in year 1 and to 22.6 (95% CI, 22.2-23.0) pills per patient in 2019. Adjusted analyses showed a 16.7% reduction in year 1 and a 27.0% reduction over the decade (P < .001). Meanwhile, adjusted allopurinol use rose by 7.8 (95% CI, 6.9-8.7) pills per patient in year 1, a 7.6% increase from baseline, and by 33.1 (95% CI, 32.6-33.7) pills per patient through 2019, a 32.0% increase from baseline over the decade (P < .001). Moreover, adjusted oral corticosteroid use exhibited no significant change in the first year, then increased by 1.5 (95% CI, 1.3-1.7) pills per patient through 2019, an 8.3% increase from baseline over the decade. Adjusted ED visits for gout rose by 0.02 (95% CI, 0.02-0.03) per patient in year 1, a 21.5% increase, and by 0.05 (95% CI, 0.04-0.05) per patient through 2019, a 39.8% increase over the decade (P < .001). Adjusted rheumatology visits for gout increased by 0.02 (95% CI, 0.02-0.03) per patient through 2019, a 10.5% increase over the decade (P < .001). In this cohort study among individuals with gout, the large increase in colchicine prices in 2010 was associated with an immediate decrease in colchicine use that persisted over approximately a decade. Substitution with allopurinol and oral corticosteroids was also evident. Increased ED and rheumatology visits for gout over the same period suggest poorer disease control.

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Comparison of benzbromarone and allopurinol on the risk of chronic kidney disease in people with asymptomatic hyperuricemia

ObjectiveThe objective of the study was to compare the relative effects of benzbromarone and allopurinol on the risk of developing chronic kidney disease in persons with asymptomatic hyperuricemia. MethodsA retrospective cohort study was conducted to analyze a 2003–2015 national database including all claims data of 2 million beneficiaries in Taiwan. Asymptomatic hyperuricemia was defined as follows: persons using urate-lowering drugs who never developed gout flares. The benzbromarone group included persons ages 20–84 that had asymptomatic hyperuricemia and received benzbromarone alone. The allopurinol group included persons ages 20–84 that had asymptomatic hyperuricemia and received allopurinol alone. The maximum follow-up time was set as 5 years in this study. The main outcome was defined as follows: persons were newly diagnosed with chronic kidney disease. A Cox proportional hazards regression analysis was performed to test the association between variables and the risk of chronic kidney disease. ResultsAfter propensity score matching, 9107 persons in the benzbromarone group and 4554 persons in the allopurinol group were eligible for the study. Approximately 71% of the study subjects were males. The mean age was 56 years old. The incidence rate of chronic kidney disease was lower in the benzbromarone group than in the allopurinol group (1.18 versus 1.99/per 100 person-years, incidence ratio = 0.60, and 95% confidence interval = 0.52–0.68).The Cox proportional hazards regression analysis disclosed that after adjusting for co-variables, there was a decreased risk of developing chronic kidney disease in the benzbromarone group as compared with the allopurinol group (hazard ratio = 0.59, 95% confidence interval = 0.52–0.67 and P<0.001). ConclusionsThe use of benzbromarone is associated with a lower hazard of developing chronic kidney disease as compared to allopurinol use among persons ages 20–84 with asymptomatic hyperuricemia. More studies are needed to confirm our findings.

P039 The association between gout and psychological co-morbidity: a five-year prospective cohort study

Abstract Background/Aims Gout is associated with physical co-morbidities and a reduction in physical health-related quality of life. However, the association between gout and psychological comorbidity (depression and anxiety) has received less attention. A secondary analysis of data from a five-year prospective cohort study was performed to determine the prevalence and incidence of anxiety and depression in people with gout, and gout characteristics associated with psychological co-morbidity. Methods Adults aged ≥18 years with gout were identified via Read codes or allopurinol prescriptions from 20 general practices across the West Midlands. Questionnaires were mailed at baseline and at 12-, 36- and 60-months. Questionnaire data included socio-demographics, gout-related characteristics (flare frequency, oligo- or poly-articular gout, gout duration and allopurinol use) and validated anxiety (GAD-7) and depression (PHQ-9) questionnaires. Current anxiety and depression were defined as scores&amp;gt;10 on the GAD-7 and PHQ-9 respectively. The prevalence and incidence of new-onset anxiety or depression were described at 12, 36 and 60 months in those without anxiety and depression at baseline. Binary logistic regression used to determine baseline gout characteristics associated with developing new-onset anxiety or depression at each time point (odds ratios (OR), 95% confidence intervals (CI), adjusted for age, gender and deprivation). Results Of 1184 baseline responders, 721, 605 and 411 responded at 12-, 36- and 60-months, respectively. The peak prevalence of both depression and anxiety was at baseline at 12.6% and 10.0%, respectively. Responders with anxiety (GAD-7 ≥10) or depression (PHQ-9 ≥10) at baseline were excluded from new-onset analysis. Over five years, one in thirteen (7.5%) developed new-onset anxiety, and one in eleven (9.2%) developed new-onset depression at any future time point. Developing anxiety was associated with a history of oligo- or poly-articular gout flares at baseline (OR 2.31, 95% CI:1.26 to 4.23) but not flare frequency, gout duration, or allopurinol use. New-onset depression was associated with allopurinol use at baseline (OR 1.93, 95% CI: 1.01 to 3.69) but not flare frequency, gout duration, or oligo- or poly-articular gout flares. Conclusion Psychological co-morbidity is common in people living with gout; clinicians should be aware of this when assessing and treating people with gout. Disclosure J.J.R. Higgs: None. L. Clarson: None. R. Bajpai: None. S. Muller: None. E. Roddy: None.

Granulomatous tattoo reaction treated with topical allopurinol.

Granulomatous reactions to tattoo ink have been frequently associated with exogenous pigment, although sometimes they are the manifestation of a cutaneous or an underlying systemic sarcoidosis. We report a case of a granulomatous reaction to a black tattoo pigment treated with 3% topical allopurinol for three months. We observed complete resolution without any side effects. Complementary examinations and follow-up ruled out sarcoidosis. Oral allopurinol has been proven to be effective for the management of granulomatous reactions to tattoos. Based on the significant improvement we have described in our patient, we recommend new studies to reveal all the potential benefits of the topical use of allopurinol for the treatment of granulomatous reactions to tattoo ink.

Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST): a multicentre, double-blinded, randomised, placebo-controlled trial.

People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference-0.17, 95% CI-0.52 to 0.17, p=0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. The British Heart Foundation and the UK Stroke Association.

Real-world treatment of gout and asymptomatic hyperuricaemia in Japan.

Recently a retrospective cohort study in Japan conducted by Koto et al. disclosed that the risk of the first gout flare would decrease 55% if serum uric acid was reduced to 5–6 mg/dl among people with asymptomatic hyperuricaemia receiving uric acid–lowering drugs as compared with untreated people (serum uric acid ≥ 8.0 mg/dl) [1]. Another study by Koto et al. published in Modern Rheumatology using the same database disclosed that the prevalence of gout was about 1.1% in Japan [2], which was lower than Taiwan (3.1%) [3].The authors commented that the low prevalence of gout in Japan could be attributed to the early drug treatment of asymptomatic hyperuricaemia based on the Japanese guideline [2, 4]. Both studies by Koto et al. provide the evidence that the natural course of asymptomatic hyperuricaemia can be changed by the intervention of uric acid–lowering drugs. Some points are discussed. First, hyperuricaemia and gout are closely related but are not the same disease. Most of the people with hyperuricaemia do not develop a gout flare during their lives [5]. Whether people with asymptomatic hyperuricaemia should take uric acid–lowering drugs to prevent the first gout flare, the academic community has not yet established a consensus. The American College of Rheumatology guideline suggests against the use of uric acid–lowering drugs to treat asymptomatic hyperuricaemia [6]. The Japanese guideline suggests that the treatment goal of hyperuricaemia is to prevent monosodium urate deposition in joints and viscera, not only leading to the risk reduction of gout flares but also leading to the risk reduction of organ damage and then leading to prolonged disease-free survival, especially cardiovascular diseases [4]. After lifestyle modification, if serum uric acid is still ≥ 9.0 mg/dl, clinicians may talk to people with asymptomatic hyperuricaemia about the current evidence of managing hyperuricaemia and possible adverse events of uric acid–lowering drugs, such as hepatotoxicity, urinary stones, and cutaneous adverse reactions. Only after informed consent is obtained, clinicians are able to consider prescribing uric acid–lowering drugs to those suitable patients [4]. Although serum uric acid ≥ 9.0 mg/dl is an independent risk factor for gout flares, there have been no randomized control studies focusing on the management of asymptomatic hyperuricaemia where the primary endpoint was set as the development of the first gout flare. Therefore, in the current situation, urate-lowering drugs are not strongly recommended for asymptomatic hyperuricaemia in order to prevent the first gout flare. Moreover, in the present guidelines, how to treat hyperuricaemia should be decided after assessing the patients’ concomitant diseases. Second, benzbromarone is a uricosuric drug to lower serum uric acid. Because of its potential hepatotoxicity, benzbromarone had been withdrawn from some markets since 2003, but it still can be prescribed in many countries including Taiwan and Japan [7]. Three case reports in Japan showed that benzbromarone could be related to fulminant hepatotoxicity, but none was confirmed by rechallenge tests [8–10]. However, no hepatotoxicity was reported in Taiwan and South Korea. Allopurinol is the first drug of choice to lower serum uric acid in western countries [6]. Allopurinol use has a potential risk to cause severe cutaneous adverse reactions. Among the three Asian countries, the incidence rate of allopurinol-related severe cutaneous adverse reactions was the highest in Taiwan (2.57/1000 person-years), followed by South Korea (2.31/1000 person-years), and the lowest in Japan (2.00/1000 person-years) [11]. In ethnic groups with a high frequency of HLA-B*5801, benzbromarone will be safer than allopurinol for the management of hyperuricaemia. The standard doses of benzbromarone (100 mg/day) are more effective in lowering serum uric acid than the standard doses of allopurinol (300 mg/day) [12]. Only higher doses of allopurinol (450 mg/day) are as equally effective in lowering serum uric acid as the standard doses of benzbromarone (100 mg/day) [12]. Third, current guidelines do not present which drug should be the first-line drug for asymptomatic hyperuricaemia. If we want to set up a new clinical guideline, it is necessary to determine which drug is more effective and safer to prevent the first gout flare in people with asymptomatic hyperuricaemia. It indicates a future research direction.

Impact of pharmacist-led collaborative gout clinic on timely achievement of serum uric acid goals

Background The concept of a pharmacist-led collaborative gout clinic is relatively new in Singapore. Objective This study examined the impact of this pilot shared care model on providing dose titration of urate lowering therapy, gout education and patient support to achieve target serum uric acid (sUA) levels. Method A retrospective pre-post study was undertaken to compare outcomes in patients who were started on either allopurinol or febuxostat in the 24 months prior to (Group A: Pre implementation) or 33 months following launch of the collaborative gout clinic (Group B: Post implementation). The collaborative gout clinic comprises of a clinical pharmacist under the supervision of a rheumatologist. Results Of 98 eligible subjects enrolled in our study, there were 50 patients (all prescribed allopurinol) for Group A and 48 patients for Group B (allopurinol n = 29, febuxostat n = 19). Among patients who achieved target sUA level of 360 μmol/L or less at 1 year of drug initiation with use of allopurinol, the median [interquartile range, IQR] time taken to attain target sUA was shorter in Group B than Group A (111 [82–308] days vs. 293 [265–414] days, p = 0.016). As compared to Group A, Group B had lesser patients experiencing gout flare (41.3% vs. 70.0%, p = 0.018) and more patients achieving target sUA (75.9% vs. 22.0%, p &lt; 0.001). Mean ± [standard deviation, SD] daily allopurinol dose to achieve target sUA levels was 276 mg ± [138 mg]. Conclusion Our results demonstrate the use of a pharmacist-led collaborative gout clinic may help to achieve better clinical outcomes in gout management.

Effect of febuxostat on adverse events and mortality in gout in Taiwan: An interrupted time series analysis

To evaluate the influence of febuxostat on adverse events and mortality in gout. We retrospectively enrolled patients with newly diagnosed gout and prescribed urate-lowering therapy between 2006 and 2017 from the Taiwan National Health Insurance Database. These patients were divided into 2 groups: with and without comorbidities (n= 294 847 and 194 539). An interrupted time series analysis with adjustments for demographics, comorbidities, and comedication by propensity score-based stabilized weights was used to compare the trend of adverse events and mortality before vs after febuxostat was introduced in 2012. The proportion of febuxostat use gradually increased from 0% in 2012 to 30% in those with comorbidities and 10% in those without comorbidities in 2017. Allopurinol use decreased from 30% in 2012 to 10% in 2017. The slope of the 1-year incidence rate of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (per 10 000 patients) significantly reduced after 2012 in those with and without comorbidities (-0.375 per quarter, P= .015 and -.253 per quarter, P= .049). The slope of the 3-year incidence rate of acute myocardial infarction (AMI) (per 1000 patients), percutaneous coronary intervention (PCI) (per 1000 patients), and all-cause mortality (per 100 patients) significantly increased after 2012 in those with comorbidities (+0.207 per quarter, P= .013; +.389 per quarter, P= .002; +.103 per quarter, P= .001). Febuxostat may reduce SJS and TEN in all gout patients but increase AMI, PCI, and all-cause mortality in gout patients with comorbidities.

Risk of Erectile Dysfunction in Male Patients with Gout Treated with Febuxostat or Allopurinol: A Propensity Score-Matched Cohort Study.

To evaluate and compare the risk of erectile dysfunction (ED) associated with the use of allopurinol and febuxostat in adult male gout patients. We conducted a cohort study using TriNetX (Cambridge, MA, USA), a global federated health research network that provides real-time electronic medical record datasets. We analyzed and compared the associated risk of ED in gout patients who started taking allopurinol or febuxostat within 12 months. Propensity score matching was performed to adjust for demographic variables, comorbidities, and medication use. Kaplan-Meier analysis was used to estimate the probability of the outcome of interest. The hazard ratio (HR) and associated confidence intervals were calculated along with the proportionality test using R's Survival Package v3.2-3. We identified 679,862 patients with gout among 107,517,445 patients in the database. Of these patients, 24,000 were treated with febuxostat and 299,726 with allopurinol. After propensity matching, 9075 patients receiving febuxostat without allopurinol (febuxostat group) and 9075 corresponding patients receiving allopurinol without febuxostat (allopurinol group) were analyzed for comparison. Among all male patients over 19 years of age, febuxostat was associated with a significantly higher risk of ED versus allopurinol (HR 1.354; 95% confidence interval (CI) 1.003-1.829; log rank test, p = 0.047). After subgroup analysis, in gout patients aged 19-64 years, a significantly higher incidence of ED was observed in the febuxostat group than in the allopurinol group (HR 2.002, 95% CI 1.282-3.126). The risk of ED did not differ significantly between the allopurinol and febuxostat groups in gout patients older than 65 years. Febuxostat may be associated with a higher risk of ED than allopurinol in adult male patients with gout. Future large-scale prospective studies are warranted to confirm our results.

Allopurinol Induction on Histopathological Structure of the Liver in Male Mice (Mus musculus)

Allopurinol is used to reduce total uric acid levels in the body into oxypurinol which can inhibit xanthine oxidase. Allopurinol inhibits the precursors of uric acid formation, xanthine, and hypoxanthine. However, consumption of the drugs can cause side effects on the liver. The aim of the research was to determine the effect of allopurinol induction on the liver histopathology of male mice (Mus musculus) DDY strain. The method used in this research was an experimental design used post-test only that was divided into 4 groups of 4 mice per group. The control group (P0) was given 0.5% Na-CMC, and groups I, II, and III (P1, P2, and P3) were induced by allopurinol at 10 mg/kg BW, 20 mg/kg BW, and 30 mg/kg BW for 14 days. Allopurinol induction was performed by oral gavage. The results of the research showed that treatment with allopurinol caused changes in the mice’s body weight, liver index, liver morphology, and histological structure of the liver tissue, including necrosis, steatosis, leukocyte infiltration, binuclear hepatocytes, hepatocyte swelling, congestion, sinusoid dilatation, and hemorrhage. The level of liver damage increased in line with the dose used. This research indicated that the higher the allopurinol level, the higher the level of alteration in the liver section structure. Long-term use of allopurinol can cause damage to the structure of mice liver (liver toxicity).

`Risk of cardiovascular disease associated with febuxostat versus allopurinol use in patients with gout: a retrospective cohort study in Korea

Febuxostat is the drug used to treat hyperuricemia in patients with gout. Recently, the usage of Febuxostat has been controversial over the side effects in cardiovascular. The study aimed to comparatively analyze the risk of cardiovascular disease associated with febuxostat and allopurinol use in Korean patients with gout. A cohort study was conducted using national insurance claim data from the Health Insurance Review and Assessment Service (HIRA). Adult patients who were diagnosed with gout and prescribed febuxostat or allopurinol more than once from July 1, 2015, to June 30, 2018 were studied. The outcome was cardiovascular disease. Analysis was performed using Cox’s proportional hazard model following 1:1 propensity score matching to estimate the hazard ratio with a 95% confidence interval. In total, 90,590 patients were defined as the final study cohort who had an average follow-up of 467 days, including 28,732 and 61,858 patients in the febuxostat and allopurinol groups, respectively. After the 1:1 propensity score matching, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.17; 95% CI: 1.10–1.24). In the sensitivity analysis, the risk of cardiovascular disease in the febuxostat group was significantly higher than in the allopurinol group (HR: 1.09; 95% CI: 1.04–1.15). However, further sensitivity analysis showed no statistically significant difference between the febuxostat group and allopurinol group after adjusting for cardiovascular disease history before the index date. Similarly, no statistically significant difference was found between the two drugs in the subgroup analysis. Febuxostat was not associated with a significantly increased risk of cardiovascular disease.

Gout in Dalarna, Sweden – a population-based study of gout occurrence and compliance to treatment guidelines

Objective This study aimed to describe the incidence and prevalence of gout, describe the use of allopurinol among prevalent gout cases, and determine persistence with allopurinol and degree of compliance with treat-to-target recommendations before and after the publication of Swedish national guidelines in 2016. Method Prospectively registered data on gout diagnoses and allopurinol prescriptions were used to calculate incidence and prevalence, and the proportion of prevalent patients on allopurinol. Gout patients starting allopurinol during 2013–2015 versus 2016–2018 were compared regarding persistence and compliance with treat-to-target principles. Results The incidence of gout was 221–247 per 100 000 person-years during 2014–2019, prevalence in 2018 was 2.45%. Among prevalent cases, the proportion on allopurinol ranged from 21% to 25%. Allopurinol persistence was better for individuals starting therapy during 2016–2018 compared with 2013–2015 (45% vs 39%, p = 0.031), as were several outcomes related to treat-to-target principles, e.g. measuring baseline serum urate (SU) (84% vs 77%, p < 0.001), follow-up SU (50% vs 36%, p < 0.001), and the proportion of patients reaching an SU level < 360 µmol/L (45% vs 30%, p < 0.001). Conclusion Incidence and prevalence were slightly higher than in previous Swedish reports. Allopurinol use among prevalent gout patients did not increase during 2014–2019. Only a minor improvement in persistence was seen, and a moderate increase in compliance with guidelines, suggesting a need for improved management and extended patient involvement to increase and optimize the use of urate lowering therapy.