Urate-lowering Therapy In Patients Research Articles

Urate lowering therapy in patients starting hemodialysis limit gout flares occurrence: ten years retrospective study

BackgroundUncontrolled gout can cause articular impairment but is also associated with a global and cardiovascular excess mortality, especially in dialysis population.Data documented within existing research is not conclusive regarding gout flares evolution during hemodialysis and their control by urate lowering therapy (ULT).Without clear guidelines concerning hemodialysis patients management with chronic gout, this study proposes to investigate whether gout flare incidence reduction could be observed on this population treated by urate lowering therapy versus patients without treatment.MethodsWe performed a retrospective cohort study in two hemodialysis centers in France. Were selected patients over 18 years old with a gout history who started hemodialysis between January 2005 and September 2015.Demographics and clinicals data were recorded at hemodialysis start and throughout 5 years of follow up. Gout flare was defined as presence of uric acid crystal in joint punction or clinically diagnosed as such with a colchicine prescription.All statistical analysis were performed in SAS® version 9.4 (SAS Institute Inc., Cary, NC).ResultsOne hundred eighty-one patients have been included, mean age at dialysis initiation was 68.6 years (± 12.4) with 72% of men, 54% were treated by ULT: 89.7% by allopurinol and 9.3% by febuxostat. One patient received both treatments successively. After hemodialysis initiation, 35.36% patients had experienced at least one gout flare. The appearance of at least one gout flare concerned 50% of patients in no ULT group and 22.68% patients in ULT group (p = 0.0002).Dialysis efficiency was measured at regular interval during follow-up and was similar in both groups.To study the association strength between clinical factors and gout flares occurrences, a Cox model was performed; ULT is a protector factor of gout flare (HR:0,42, CI 95: 0,25-0,71).The proportion of serum urate values within the target (median 53% vs 29.3%, p < 0.0001) was significantly higher in ULT group versus no ULT group (median 53% vs 29.3%, p < 0.0001).ConclusionUrate lowering therapy limit new gout flares occurrence in hemodialysis patients with gout historyCollaboration between rheumatologists and nephrologists may help to update guidelines for urate-lowering therapies in patients on dialysis.

Colchicine for cardiovascular and limb risk reduction in Medicare beneficiaries with peripheral artery disease: emulation of target trials.

Recent evidence from randomized trials demonstrates that colchicine can reduce the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease. Colchicine's effect on lower-extremity peripheral artery disease (PAD) is not known. To make inferences about the real-world effectiveness of colchicine in PAD, we emulated two target trials leveraging the variable prescribing practice of adding colchicine vs. a non-steroidal anti-inflammatory drug (NSAID) to urate-lowering therapy in patients with gout and PAD. Emulated Trial 1 compared colchicine initiators with NSAID initiators. Emulated Trial 2 compared long-term (indefinite) and short-term (3 months) treatment strategies after initiating colchicine. Eligible individuals were those continuously enrolled in Medicare receiving care at a multicentre academic health system between July 2007 and December 2019. The primary outcome for both trials was a 2 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. Inverse probability weighting was used to adjust for confounding. Percentile-based 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. A total of 1820 eligible patients were included; the mean age was 77 years [standard deviation (SD) 7], 32% were female, and 9% were non-White. The mean (SD) duration of colchicine and NSAID therapy was 247 (345) and 137 (237) days, respectively. In the emulation of Trial 1, the risk of the primary composite outcome of MALE, MACE, and death at 2 years was 29.9% (95% CI 27.2%, 32.3%) in the colchicine group and 31.5% (28.3%, 34.6%) in the NSAID group, with a risk difference of -1.7% (95% CI -6.5%, 3.1%) and a risk ratio of 0.95 (95% CI 0.83, 1.07). Similar findings were noted in the emulation of Trial 2, with a risk of the primary composite outcome at 2 years of 30.7% (95% CI 23.7%, 38.1%) in the long-term colchicine group and 33.4% (95% CI 29.4%, 37.7%) in the short-term group, with a risk difference of -2.7% (95% CI -10.3%, 5.4%) and risk ratio of 0.92 (95% CI 0.70, 1.16). In a real-world sample of patients with PAD and gout, estimates of the effect of colchicine were consistent across two analyses and provided no conclusive evidence that colchicine decreased the risk of adverse cardiovascular or limb events and death. The cardiovascular and limb benefits of colchicine in older, comorbid populations with PAD and advanced systematic atherosclerosis remain uncertain.

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

Elevated serum uric acid (sUA) is associated with heart failure (HF). Urate-lowering therapy (ULT) in HF is associated with lower risk of HF hospitalization (hHF) and mortality. 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. 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. ULT was associated with reduced risk of adverse clinical outcomes in patients with HF and gout or hyperuricemia over 5 years.

Влияние бессимптомной гиперурикемии на течение, исходы и коморбидные состояния при системной красной волчанке. Современный взгляд на проблему

The considerable prevalence of asymptomatic hyperuricemia (HU) in the general population underscores the need for an in-depth investigation into its impact on the progression of various diseases, including rheumatological and comorbid conditions. This literature review elucidates the association between HU and systemic lupus erythematosus (SLE) and examines the pathogenetic and clinical foundations for implementing urate-lowering therapy in individuals with concurrent HU and SLE. It has been demonstrated that elevated serum uric acid (UA) levels correlate with an increased risk of pulmonary hypertension, stroke, arterial hypertension, hyperlipidemia, and metabolic syndrome. The mechanisms through which HU contributes to renal damage are explored independently, highlighting the challenges in ascertaining the primary etiology of renal disorder. Although direct interventional studies validating the necessity of urate-lowering therapy in patients with SLE, HU, and comorbidities (particularly cardiovascular diseases) are not currently available, there is substantial evidence supporting the beneficial impact of UA level normalization on cardiovascular outcomes. Given the negative impact of elevated UA levels on comorbid conditions that crucially influence the life expectancy of SLE patients (such as cardiovascular disease and chronic kidney disease), lifelong management of UA levels is advisable for individuals with SLE. KEYWORDS: systemic lupus erythematosus, hyperuricemia, comorbidity, metabolic syndrome, comorbid conditions, urate-lowering therapy. FOR CITATION: Musiychuk M.M., Gaydukova I.Z., Inamova O.V., Aparkina A.V., Rebrov A.P. Asymptomatic hyperuricemia effect on the course, outcomes and comorbid conditions in systemic lupus erythematosus. Modern view of the problem. Russian Medical Inquiry. 2024;8(7):391–399 (in Russ.). DOI: 10.32364/2587-6821-2024-8-7-4.

Prospects for prescription of urate-lowering therapy in patients with asymptomatic hyperuricemia and gout

Gout is a chronic disease characterized by attacks of arthritis, most often of the lower extremities, which develop under conditions of prolonged hyperuricemia caused by environmental and/or genetic factors. In the last decade, there has been an increase in the prevalence of both hyperuricemia and gout, which causes concern not only among rheumatologists, but also among doctors of related specialties. This is due to the fact that uric acid, deposited not only in joints, but also in other organs and tissues, contributes to the development of cardiovascular and metabolic diseases, as well as chronic kidney disease and osteoarthritis. It has been proven that even asymptomatic hyperuricemia, and not just hyperuricemia as a component of clinical gout, contributes to a more severe course of these comorbid pathologies. Probably, the maintenance of a chronic systemic inflammatory process, oxidative stress and the formation of endothelial dysfunction play a decisive role in the nosogenesis of polypathology. Accumulated scientific evidence suggests that achieving target levels of uric acid (less than 360 μmol/L in the case of atophus gout and less than 300 μmol/L in the case of tophi gout) leads to a reduction in the incidence of cerebral, cardiovascular, and renal events. Prescribing urate-lowering drugs to patients with hyperuricemia and at risk for type 2 diabetes mellitus and osteoarthritis also appears promising. Among the urate-lowering drugs registered in the Russian Federation, febuxostat shows the highest efficiency and safety, and also has a nephroprotective effect, which is especially important in patients with a decrease in glomerular filtration rate.The article examines in detail the effect of febuxostat on various organs and systems in patients with gout and asymptomatic hyperuricemia.

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.

Association between urate-lowering therapy and cardiovascular events in patients with asymptomatic hyperuricemia.

To investigate the role of urate-lowering therapy (ULT) in the prevention of cardiovascular disease (CVD) in patients with asymptomatic hyperuricemia using the Japanese healthcare record database. This retrospective cohort study used data from the JMDC Claims Database, which includes records of medical check-ups and Japanese health insurance claims. Subjects aged at least 18years with a serum uric acid (sUA) level ≥ 7.0mg/dL and at least one medical check-up from January 2007 to August 2021 were included in this study. The exposure was any ULT prescription, and the primary outcome included composite CVD outcomes, including coronary artery disease, stroke, and atrial fibrillation. Analysis was performed with a new-user design and overlap weighting to balance the baseline characteristics of the subjects. Cox proportional hazards models were used to investigate the association between ULT and the development of CVD. In total, 152,166 patients were included in the main analysis before overlap weighting in this retrospective cohort study. The number of subjects in the ULT group was 5,270, and there were 146,896 subjects in the control group. Composite CVD outcomes were observed in a total of 7,703 patients. The risk of developing composite CVD outcomes was not different between the ULT group and the control group (HR: 1.01, 95% CI: 0.89 to 1.13). ULT for patients with asymptomatic hyperuricemia did not prevent the development of CVD based on the Japanese claims database. Key points • Among subjects with asymptomatic hyperuricemia, ULT was not associated with a lower risk of CVD • There was no appropriate cutoff for initiating ULT in patients with asymptomatic hyperuricemia • There was no appropriate cutoff as the therapeutic goal of ULT in patients with asymptomatic hyperuricemia.

Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database.

We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database. Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis. This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041). Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.

Cardiovascular and kidney outcomes of uric acid-lowering therapy in patients with different kidney functions: study protocol for a systematic review, pairwise and network meta-analysis

IntroductionHyperuricaemia has been implicated in the development of kidney function in populations with chronic kidney disease; however, the benefits of urate-lowering therapy (ULT) remain uncertain in different clinical studies. The...

Efficacy and safety of urate-lowering therapy in multimorbid patients in real clinical practice: results of clinical study

Background. Clinical studies of urate-lowering therapy (ULT) use in multimorbid patients, including those with chronic kidney disease (CKD), are important in modern medical science. The purpose was to determine the efficacy and safety of ULT in patients with hyperuricemia and comorbid conditions, including people with chronic kidney disease, in real clinical practice. Materials and methods. This prospective comparative clinical study “Liquestia: comparative efficacy and safety in gouty arthritis patients with comorbid diseases and in patients with hyperuricemia and chronic kidney disease” was conducted in real clinical practice with the involvement of 124 patients with hyperuricemia, who were prescribed either febuxostat (Liquestia, JSC “Farmak”/Adenuric, Berlin Chemie) or allopurinol as ULT. Results. Individuals who received febuxostat significantly more often and faster reached the target levels of uric acid compared to patients who underwent treatment by allopurinol, regardless of glomerular filtration rate (GFR), except those from dialysis subgroup, and the presence of comorbidities. Patients in febuxostat subgroups during the study showed an increase in GFR after 6 months of treatment — at the level of the trend in the group with baseline GFR ≥ 60 ml/min and at a statistically significant level — in CKD stage 3–4, which could be the evidence of renoprotective effect of febuxostat with reduced GFR, while people receiving allopurinol tended to further decrease of GFR in 31.8 % of cases. Conclusions. The use of Liquestia for the treatment of patients with hyperuricemia and various comorbid conditions is no less effective than the use of Adenuric and more effective than allopurinol and helps achieve the target levels of uric acid in 90 % of cases within 6 months of treatment, which accompanied by a statistically significant increase in GFR in patients with CKD stage 3–4.

Early urate-lowering therapy in gouty arthritis with acute flares: a double-blind placebo controlled clinical trial

BackgroundGouty arthritis (GA) is a chronic systemic disease with recurrent acute monoarthritis. In a previous study, a higher incidence of acute flares was observed during the initial marked decrease in serum urate level. Our study evaluated the effect of early urate-lowering therapy in patients with acute GA flares.MethodsThis study included 40 patients with acute GA; of them, 20 received colchicine 0.5 mg colchicine twice daily, while 20 received probenecid 500 mg and colchicine 0.5 mg twice daily. We evaluated GA severity and laboratory data for 2 weeks after the initial therapy. Medians and interquartile ranges (IQRs) were calculated to evaluate clinical presentations between these two groups.ResultsRapidly decreasing median serum uric acid levels was found in the patients treated with probenecid and colchicine compared with the patients treated with colchicine alone on day 8 (− 1.9 [IQR, − 3.7 to 0] vs 0.8 [IQR, − 0.1–2.2]; P < 0.001). However, the median decrease in visual analog scale score did not differ significantly between the two groups (− 5.5 [IQR, − 8.0 to − 3.0] vs − 3.5 [IQR, − 5.9 to − 2.0]; P = 0.080).ConclusionNo significant increase was noted in acute gout flare severity or duration among GA patients treated with early aggressive control of hyperuricemia using probenecid plus colchicine.

Atrial Fibrillation Risk and Urate-Lowering Therapy in Patients with Gout: A Cohort Study Using a Clinical Database.

Individuals of Asian descent are at higher risk for developing hyperuricemia and gout as compared to Western populations. Urate-lowering therapy (ULT) is an effective treatment for hyperuricemia and gout. It was reported that febuxostat, one of the ULTs, raises the risk of atrial fibrillation (AF) in elderly populations. Nevertheless, this association has not been properly investigated in Asian populations. We aimed to investigate the development of AF after ULT with different drugs in an Asian population. We conducted a retrospective cohort study using the clinical database at Kaohsiung Veterans General Hospital. Patients newly diagnosed with gout between 1 January 2013 and 31 December 2020 and with a documented baseline serum uric acid (sUA) level but no prior diagnosis of AF were identified. Patients were divided into three groups-allopurinol, benzbromarone, and febuxostat users. During the follow-up period, the risks of incident AF following the initiation of ULT with different drugs were assessed. Development of incident AF was noted in 43 (6%) of the 713 eligible patients during the follow-up period (mean, 49.4 ± 26.6 months). Febuxostat-treated patients had a higher prevalence of certain comorbidities (diabetes mellitus, heart failure, and chronic kidney disease) and higher CHA2DS2-VASc scores. Compared with allopurinol, neither febuxostat nor benzbromarone was associated with increased adjusted hazard ratios (HR) for incident AF (HR: 1.20, 95% confidence interval [CI]: 0.43-3.34; HR: 0.68, 95% CI: 0.22-2.08). There was no difference in the risk of incident AF among Asian patients with gout who received febuxostat, allopurinol, or benzbromarone. Further studies are needed to evaluate long-term cardiovascular outcomes in patients receiving different ULT drugs.

Urate-lowering therapy for patients with gout on hemodialysis.

ObjectiveGout is the most common form of inflammatory arthritis and is caused by deposition of monosodium urate crystals resulting from a high burden of uric acid (UA). High UA burden also has been associated with increased morbidity and mortality in the general population and progression to chronic kidney disease. In persons with gout and end‐stage renal disease (ESRD), prior studies suggest that UA levels decrease after initiation of hemodialysis (HD). We evaluated UA level and the use of urate‐lowering therapies (ULTs) in patients with gout and ESRD on HD.MethodsWe performed a retrospective review of patients with gout and ESRD seen at a large urban public hospital (The MetroHealth System). We extracted data from the medical record (Epic) for patients diagnosed with gout and ESRD on HD. The main outcomes were the UA level and the use of ULTs before and after HD initiation.ResultsWe identified 131 patients with gout on HD. Of these, 21 patients had crystal proven gout diagnosis, 10 of whom had data on UA level pre‐HD and post‐HD and were included in the analysis. For the total sample (N = 21), the mean age was 65 years, 7 were female and 20 were African American. Mean pre‐HD and post‐HD UA levels were 8.4 and 3.98 mg/dL respectively. Twenty‐one patients were receiving ULT pre‐HD, 11 discontinued post‐HD.ConclusionAmong patients with gout and ESRD, we observed a decrease in UA level associated with initiation of HD. For this group, discontinuation of ULTs may be appropriate.

Efficacy of Urate–Lowering Therapy in Patients With Chronic Kidney Disease: A Network Meta-Analysis of Randomized Controlled Trials

The goal of this study was to systematically review the efficacy and safety of urate-lowering therapy in patients with chronic kidney disease (CKD). PubMed, the Cochrane Central Registration of Controlled Trials, and EMBASE databases and several websites were electronically searched to collect randomized clinical trials on the efficacy of urate-lowering therapy in CKD from inception to December 31, 2020. The key primary end points were uric acid or estimated glomerular filtration rate (eGFR) levels; the safety end points were death, renal event, cardiovascular event, and gastrointestinal event. A Bayesian network meta-analysis was conducted with the use of ADDIS and R software. A total of 17 randomized clinical trials involving 2059 patients were included. The results of network meta-analysis showed that urate-lowering therapy could reduce urate levels in patients with CKD. Febuxostat was the most effective treatment in lowering urate levels according to the rank probability. Urate-lowering therapy has the tendency to delay the decline of eGFR, but the difference was not statistically significant. Ranking probability showed that benzbromarone, febuxostat, and allopurinol ranked higher than placebo in reducing the decline of eGFR. There were no statistically significant differences between groups in the incidence of all adverse effects. All urate-lowering therapies could reduce the urate level in patients with CKD, but the benefit of such therapy in renal disease is still unclear. PROSPERO identifier: CRD42020222601.

Clinical interventions to improve adherence to urate-lowering therapy in patients with gout: a systematic review.

The aim of this study was to systematically review and compare the quantitative effect of clinical interventions designed to improve adherence to urate-lowering therapy. MEDLINE, Embase, CINAHL, Scopus and Web of Science were searched for interventional studies reporting quantitative adherence to urate-lowering therapy information as an endpoint. Intervention details, quantitative adherence information, clinical outcome and cost-effectiveness data were extracted. Risk of bias was assessed. From 4721 records, 11 studies (3 randomised and 8 observational) met the inclusion criteria. Pharmacist- and nurse-led interventions were described, involving a mixture of patient education, telephone or mobile texting reminders, and medication blister packing. Quantitative adherence information was obtained using methods such as patient self-reporting and pharmacy-dispensing data. Most studies had a moderate-to-high risk of bias. Two of the three randomised studies reported improvement in adherence between the intervention and control groups, including a 13% increase in the mean proportion of days covered >0.8 [341/681 participants (50%) versus 289/782 participants (37%)] and an 88% increase in achieving a high Medicine Taking Behaviour questionnaire score [37/42 participants (88.1%) versus 0/40 participants (0%)]. Four of the eight observational studies reported improved adherence from baseline (ranging from 33% to 91% based on the longitudinal change in adherence metrics reported). A comparison of the different types of interventions was not feasible due to the heterogeneity between study designs and adherence metrics used. These findings support the need for more interventional studies to be conducted to aid adherence management.

Association of the Q141K polymorphism of the ABCG2 gene with the effectiveness of urate-lowering therapy in patients with gout (a pilot study)

Achieving the target serum uric acid (UA) level is a priority in the treatment of gout.Objective: to study the relationship of the ABCG2 gene polymorphism (rs2231142) with the efficacy of allopurinol and febuxostat in patients with gout.Patients and methods. The study included 82 patients with gout over 18 years of age with serum UA level &gt;360 μmol/L who did not take uratelowering therapy.All patients were prescribed allopurinol 100 mg daily, followed by its titration until the target UA level was reached (&lt;360 μmol/L or &lt;300 μmol/L in patients with chronic tofus gout), up to a maximum of 900 mg/day, in patients with glomerular filtration rate &lt;60 ml/min/1.73 m2 – up to 300 mg/day. Patients who did not reach the target UA level when using allopurinol were prescribed febuxostat 80 mg/day, which, if necessary, was increased to 120 mg/day. Monitoring of each patient was continued until the target serum UA level was reached.All patients underwent genotyping of the C&gt;A polymorphism (rs2231142) of the ABCG2 gene. We compared the probability of achieving the target UA level, the mean values of a decrease in the serum UA level, and the mean doses of urate-lowering drugs in patients with different genotypes (CC, CA, AA) of the ABCG2 gene.Results and discussion. The target UA level in 45 (55%) of 82 patients was defined as &lt;300 μmol/L, in the remaining 37 – as &lt;360 μmol/L.In 26 patients, the dose of allopurinol did not exceed 300 mg/day. In 28 (34%) patients treated with allopurinol, the target UA level was achieved, in the remaining 54 (66%) patients, allopurinol was substituted by febuxostat, and in 22 (41%) of them the UA level decreased and was below the target.The CC genotype of the ABCG2 gene was detected in 51 (62%) patients, the CA genotype in 30 (37%) and the minor genotype AA in 1 (1%).The probability of achieving the target UA level during therapy with allopurinol in carriers of homozygous CC genotype and genotypes CA or AA did not differ: 17 (33%) and 11 (35%) cases, respectively, but patients with CA and AA genotypes required a significantly higher dose of allopurinol (365±102 mg/day) than patients with the CC genotype (290±85 mg/day), p=0.002. Of the 54 patients who took febuxostat and did not reach the target UA level, 30 (56%) had the CC genotype and 24 (44%) had the CA genotype, the probability of reaching the target UA level was also comparable (p=0.22).Conclusion. The probability of reaching the target serum UA level in patients with gout taking allopurinol is not associated with the C&gt;A polymorphism of the ABCG2 gene, but the presence of CA and AA genotypes is identified with a higher dose of the drug. The C&gt;A (rs2231142) polymorphism of the ABCG2 gene does not affect the ability to achieve the goal of therapy when using febuxostat in patients with allopurinol ineffectiveness.

Urate-lowering Therapy and Chronic Kidney Disease Development in Patients with Gout.

Objectives: Chronic kidney disease (CKD) has emerged as a global health concern. Many studies have identified an association between hyperuricemia and CKD, and some studies have revealed that urate-lowering therapy (ULT) can attenuate CKD progression. However, only a few studies have explored the role of ULT in the prevention of new onset CKD.Methods: To compare the risk of incident CKD between users and nonusers of ULT in patients with gout, we conducted a 13-year population-based retrospective cohort study. Overall incidence of CKD was compared between 7126 ULT users and 7126 matched ULT nonusers.Results: The CKD incidence rate for both the users and nonusers of ULT was 1.7 per 100 person-years, after adjusting for sex, age, region of residence, comorbidities, and medications used. No significant difference in CKD risk (adjusted hazard ratio [aHR]: 0.97; 95% confidence interval [CI]: 0.88-1.07) was noted between the ULT users and nonusers. In the subgroup of patients with diabetes mellitus (DM) and without hypertension (HT), ULT tended to be associated with lower risk of incident CKD (aHR: 0.52; 0.95% CI: 0.28-0.97). Compared with the risk of new onset CKD in patients receiving xanthine oxidase inhibitors, those receiving uricosuric agents seemed to have a lower risk of developing CKD (aHR: 0.81, 95% CI: 0.67-0.99).Conclusion: This population-based cohort study indicated that ULT is not associated with lower risk of CKD development. However, in the subgroup of patients with DM and without HT, ULT is associated with significantly lower risk of incident CKD.

Features of the course of rheumatoid arthritis and osteoarthritis in patients with asymptomatic hyperuricemia

Introduction. According to numerous studies, the prevalence of asymptomatic hyperuricemia has increased in most countries. Uric acid is an important biomarker of the cardiovascular system, and there are now quite a big number of sources indicating its role in the development of a some chronic metabolic conditions, cardiovascular disease and associated mortality. At present, there is no consensus on the need for urate-lowering therapy in patients with asymptomatic hyperuricemia. There is a limited number of studies examining the problem of asymptomatic hyperuricemia in patients with rheumatic diseases, the features of comorbidity in these conditions, the frequency and effectiveness of urate-lowering therapy.&#x0D; Purpose. To study the peculiarities of the course of rheumatoid arthritis and osteoarthritis with associated asymptomatic hyperuricemia and compare them with the ones associated with arthragra.&#x0D; Materials and methods. The analysis was performed on the basis of the data collected from the city register of the patients with arthragra and asymptomatic hyperuricemia in St. Petersburg. The data collected included the medical records of 1725 patients with arthragra, 433 patients with rheumatoid arthritis and hyperuricemia and 355 patients with osteoarthritis and hyperuricemia.&#x0D; Results. The patients with rheumatoid arthritis and hyperuricemia were more likely to have increased erythrocyte sedimentation rate and C-reactive protein, the highest medium level of erythrocyte sedimentation rate; acute myocardial infarction, chronic heart failure, gallstone disease and non-alcoholic fatty liver disease were more frequently detected. The patients with osteoarthritis and hyperuricemia were more likely to have high total cholesterol, at its highest medium level; stable angina, arrhythmia, varicosity, obesity, prediabetes and type 2 diabetes mellitus were more likely to be detected. Kidney damage was detected more frequently in the patients with arthragra. In the group of rheumatoid arthritis and hyperuricemia urate-lowering therapy was started in 30.95% of the patients, in the group of osteoarthritis and hyperuricemia in 36.06%.&#x0D; Conclusions. In rheumatic diseases, hyperuricemia is a common associated condition. Their combination leads to increased risk and frequency of cardiovascular, metabolic and gastroenterological comorbidity. The prescription of urate-lowering therapy to the patients with rheumatic diseases and asymptomatic hyperuricemia with high cardiovascular risk led to the target uric acid levels in 34.58% of the patients with rheumatoid arthritis and 52.08% of the patients with osteoarthritis.

Interventions to improve uptake of urate-lowering therapy in patients with gout: a systematic review.

BackgroundGout treatment is suboptimal despite available therapy, with low levels of initiation and persistence of urate-lowering therapy (ULT) in many patients.AimTo identify all interventions that have attempted to improve the uptake of ULT and analyse the clinical outcomes.Design & settingA systematic review of international articles published in English.MethodA systematic search was conducted through MEDLINE, Embase, CINAHL Plus, and Scopus databases to identify all studies on relevant interventions for gout. Interventions were included if they aimed to address patient adherence with serum urate (SU) level as an outcome. This included patient education, practitioner monitoring, medication titration, SU monitoring, and ongoing patient engagement and follow-up. Follow-up studies to original interventions and those with only an abstract available were included.ResultsTwenty articles met the inclusion criteria, describing outcomes of 18 interventions conducted in primary care settings: six nurse-led, five pharmacist-led, and seven multidisciplinary, multifaceted interventions. Improvement in SU levels was observed in all interventions. Nurse-led interventions were effective at empowering patients as they addressed illness perceptions and provided education, advice, and telephone follow-up. Pharmacist-led interventions primarily aimed to monitor patients, alter medication dosage, and provide automated telephone follow-up. Various multifaceted programmes involving a range of providers resulted in increased sustained use of urate-lowering medication.ConclusionA nurse-led approach focusing on patient understanding about gout is the most effective in achieving improved patient adherence, and lowered SU levels among patients. An intervention should include patient education and follow-up components.

Comparison of persistence rates between allopurinol and febuxostat as first-line urate-lowering therapy in patients with gout: an 8-year retrospective cohort study.

Lifelong urate-lowering therapy (ULT) with xanthine oxidase inhibitors (XOIs), such as allopurinol and febuxostat, is the cornerstone of gout treatment. This study aimed to compare drug persistence between allopurinol and febuxostat as first-line ULT in patients with gout in real practice. In this retrospective cohort study, we evaluated 602 patients with gout in whom allopurinol or febuxostat was newly initiated from December 2011 to November 2018 at a tertiary rheumatology centre. Persistence was defined as the duration from the first description date to the end of treatment with XOIs or the end of the study period (November 2019). Among the 602 gout patients, the mean age was 60.2years and 234 (38.9%) patients had tophi. Allopurinol and febuxostat were started in 237 (39.3%) and 365 (60.6%) patients, respectively. During the study period, 282 (46.8%) patients stopped taking XOIs, and the most common reason for XOI withdrawal was poor health literacy (61.3%). The 1- and 5-year persistence rates of XOIs were 67.2% and 40.9%, respectively. In the Kaplan-Meier analysis, persistence rates of allopurinol were significantly lower than those of febuxostat (p < 0.001). In the multivariable Cox regression model, allopurinol use was a significant risk factor for discontinuation of XOIs (HR = 2.01, p < 0.001). In addition, the presence of tophi and symptom duration < 24months was independently associated with a higher risk of XOI withdrawal. Long-term persistence of XOIs was suboptimal, and allopurinol had worse persistence rates than febuxostat among patients with gout. Key Points • Long-term persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) among patients with gout was suboptimal, and the major reason for XOI discontinuation was poor health literacy in our study. • We demonstrated that allopurinol had worse persistence rates than febuxostat among patients with gout, suggesting that febuxostat is a better option for long-term ULT in light of medication adherence in a real-world setting. • Patients with gout with tophi and shorter symptom duration were found to be at high risk for poor persistence of XOIs.