Target sUA Research Articles

Baseline gut microbiome as a predictive biomarker of response to probiotic adjuvant treatment in gout management

Gout is characterized by dysregulation of uric acid (UA) metabolism, and the gut microbiota may serve as a regulatory target. This two-month randomized, double-blind, placebo-controlled trial aimed to investigate the additional benefits of coadministering Probio-X alongside febuxostat. A total of 160 patients with gout were randomly assigned to either the probiotic group (n = 120; Probio-X [1 ×1011 CFU/day] with febuxostat) or the placebo group (n = 40; placebo material with febuxostat). Coadministration of Probio-X significantly decreased serum UA levels and the rate of acute gout attacks (P < 0.05). Based on achieving a target sUA level (360 μmol/L) after the intervention, the probiotic group was further subdivided into probiotic-responsive (ProA; n = 54) and probiotic-unresponsive (ProB; n = 66) subgroups. Post-intervention clinical indicators, metagenomic, and metabolomic changes in the ProB and placebo groups were similar, but differed from those in the ProA group, which exhibited significantly lower levels of acute gout attack, gout impact score, serum indicators (UA, XOD, hypoxanthine, and IL-1β), and fecal gene abundances of UA-producing pathways (KEGG orthologs of K13479 and K01487; gut metabolic modules for formate conversion and lactose and galactose degradation). Additionally, the ProA group showed significantly higher levels (P < 0.05) of gut SCFAs-producing bacteria and UA-related metabolites (xanthine, hypoxanthine, bile acids) after the intervention. Finally, we established a gout metagenomic classifier to predict probiotic responsiveness based on subjects’ baseline gut microbiota composition. Our results indicate that probiotic-driven therapeutic responses are highly individual, with the probiotic-responsive cohort benefitting significantly from probiotic coadministration.

Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes-results from the NOR-Gout study.

Patients with gout need to adhere to medication over time to achieve good outcomes. We assessed self-reported adherence to medication with urate lowering therapy (ULT) 5 years after a treat-to-target intervention and studied how non-adherence was related to baseline demographic and disease variables. Patients in the NOR-Gout observational study were included after a recent gout flare and serum urate >360 µmol/L. Patients (mean age 56.2 (S.D. 13.6), 94.5% males, 17.2% with tophi) attended tight-control visits over one year with escalating urate lowering therapy using a treat-to-target strategy. Five-year follow-up included the Medication Adherence Report Scale (MARS-5) questionnaire (range 5-25) for adherence. Flares and SUA target achievement were compared for 5-year adherence to medication. At 5-years most of the 163 patients used ULT (95.1%). MARS-5 adherence scores after 5 years were high (median 24, interquartile range 22-25). Patients in the lowest MARS-5 quartile had, compared to the highest quartile, more often a flare during the last year of follow-up (33.3% vs. 9.5%, P=0.004), and reached the 5-yr serum urate treatment target less frequently (45.2% vs. 87.5%, P<0.001). Baseline lower age (OR 0.56, 95%CI 0.39-0.79), non-European origin (OR 0.22, 95%CI 0.06-0.80), lower SF-36 mental health scores (OR 0.94, 95%CI 0.91-0.98) and less joint pain during last flare (OR 0.73, 95%CI 0.58-0.92) were independent risk factors for non-adherence to medication. Patients reported after 5 years high adherence to medication. Non-adherence was related to more flares and less urate target achievement. Younger age and non-European origin were associated with non-adherence.

Lifestyle factors predict gout outcomes: Results from the NOR-Gout longitudinal 2-year treat-to-target study

ObjectiveGout is associated with lifestyle, body mass index (BMI) and comorbidities, including dyslipidaemia. We studied how in actively treated patients, anthropometric measures and lipid levels changed over 2 years and...

Lessons to be learned from real life data from 98 gout patients using benzbromarone

Aim: This study aims to analyze the efficacy and safety of benzbromarone as uricosuric, in a real-life clinical setting of a retrospective hospital-based gout cohort. Methods: Data from gout patients were retrieved from the digital hospital dossiers. Demographics, clinical variables, and laboratory parameters were collected at baseline and 6 months. Efficacy was measured by reaching a serum uric acid (sUA) target &lt; 0.30 mmol/L at 6 months, and the fractional excretion of uric acid (FeUA) was used as a parameter with a potential predictor value. Results: Data from 98 gout patients were analyzed. Patients were 70 (± 12) years of age, and 90% were male. After 6 months of treatment, 68 out of 98 patients (69%) reached a sUA level &lt; 0.30 mmol/L (5 mg/dL). In patients with a FeUA &lt; 4.5%, so-called low excretors, the FeUA increase was most impressive from 3.2% (± 1.0%) to 12.1% (± 6.9%) after 6 months of benzbromarone treatment (mean increase +8.9% [95% confidence interval (CI): +6.5 to +11.5%], P &lt; 0.001). In non-low excretors, FeUA was on average 7.3% (± 5.1%) and increased to 9.7% (± 6.1%): a mean +2.1% change (95% CI: –2.2 to +6.6%). The increase differed insignificantly in low versus non-low excretors: P &gt; 0.05. Four patients stopped benzbromarone treatment because of a progressive decline in renal function, a condition that was already present before benzbromarone was initiated. Remarkably 38% of patients still using benzbromarone after 3.8 (± 3.4) years of treatment. Conclusions: Using the uricosuric benzbromarone in real-life gout patients proved effectivity in lowering sUA levels within 6 months by increasing FeUA significantly. Particularly low excretors benefit from benzbromarone treatment manipulating this mode of action. Determining FeUA in gout patients may further help to find the patient profile benefiting the most from benzbromarone treatment.

Real-life results of urate-driven pharmacotherapy with three urate lowering drugs in gout: allopurinol, febuxostat and benzbromarone

Aim: This study aims to assess outcomes of gout patients from the treat to target (T2T) perspective at 6 months and 12 months while using urate lowering therapy (ULT): allopurinol, febuxostat, and/or benzbromarone. Methods: All gout patients visiting the Rheumatology department between 2015 to 2021 were identified from the digital hospital system. The diagnosis of gout was based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2015 classification criteria. Patient outcomes were predefined intention to treat (ITT) categories: category 1: patients with serum uric acid (sUA) ≤ 0.360 mmol/L (ACR target for gout); category 2: patients with sUA ≤ 0.300 mmol/L (ACR/EULAR target for severe gout); category 3: patients with sUA &gt; 0.360 (failure to meet ACR target). Results: Gout diagnoses were present in 1,186 patients: 986 (83.1%) males and 200 (16.9%) females. A follow-visit at 6 months was present in 76.9% (n = 856) out of 1,113 patients reaching sUA &lt; 0.36 mmol/L, but 257 (23%) failed to reach the 0.36 mmol/L target. At 12 months, a follow-up visit was available in 792 (71.1%) patients, and from these, 710 (90%) had reached sUA &lt; 0.36 mmol/L target. The use of benzbromarone was a strong predictor of reaching the sUA &lt; 0.30 mmol/L target: odds ratio (OR) 3.2, 95% confidence interval (CI) (1.735, 6.017) at 6 months. Diabetic patients had the highest proportion of not reaching the target: 18%. Male patients needed higher dosages of allopurinol to reach the sUA target at 6 months compared to female patients. Conclusions: This is a large study on a T2T approach based in a real-life clinical setting. Only 42% reached the sUA target at 6 months with allopurinol 300 mg quaque die (QD) monotherapy. About 77% of gout patients reach the predefined sUA target of 0.36 mmol/L at 6 months with the availability of three ULTs. There is still a significant unmet need in gout as many patients failed to achieve predefined sUA targets.

Realities of modern urate-reducing therapy for gout

Introduction. In the treatment of a patient with gout, it is important to achieve the target level of uric acid (UA) &lt; 360 μmol/l, which reduces the frequency of acute attacks of arthritis and improves the prognosis of comorbid diseases. Relief of acute gouty arthritis causes much less difficulty compared with the appointment of urate-l owering therapy (UST). The reasons for not achieving the target level of MC can be both objective and subjective.Aim. To analyze the objective and subjective components of the activity and effectiveness of UST in real outpatient practice.Material and methods. A cross- sectional study of 117 randomly selected outpatient records of patients diagnosed with gout. Mean age 58.6 ± 13.1, mean UA level 423.7 ± 122.4 μmol/L. Additionally, an anonymous survey of doctors and patients with gout was conducted on the issues of UST.Results. Patients with gout in the analyzed group were characterized by a high degree of polymorbidity: women and men, respectively, had arterial hypertension in 100 and 79%, type 2 diabetes mellitus in 39 and 23%, osteoarthritis in 73 and 57%. With inevitable polypharmacy, UST was prescribed in 37.6% of patients. Achievement of target levels of UA was registered in 23.8% of men and 39.4% of women. Failure to achieve the target sUA was associated with diuretics, elevated creatinine, and body mass index. Physicians were more than 70% active in prescribing UST, but knowledge of a single target UA level was demonstrated by 6 to 13%, depending on work experience, with an excessive assumption of UST use during an acute gout attack (19 to 36.5%). Conclusion. All components of the diagnostic and therapeutic process of curing a gouty patient need to be improved.

Course and predictors of work productivity in gout - results from the NOR-Gout longitudinal 2-year treat-to-target study.

In patients with gout there is a lack of longitudinal studies on the course of work productivity. We explored longitudinal changes in and predictors of work productivity over 2 years. Patients in the NOR-Gout observational study with a recent gout flare and serum urate (sUA) >360 µmol/l attended tight-control visits during escalating urate lowering therapy according to a treat-to-target strategy. From the Work Productivity and Activity Impairment (WPAI) questionnaire, scores for work productivity and activity impairment were assessed over 2 years together with the Beliefs about Medicines Questionnaire and a variety of demographic and clinical variables. At baseline patients had a mean age of 56.4 years and 95% were males. WPAI scores at baseline were 5.0% work missed (absenteeism), 19.1% work impairment (presenteeism), 21.4% overall work impairment and 32.1% activity impairment. Work productivity and activity impairment improved during the first months, and remained stable at 1 and 2 years. Comorbidities were not cross-sectionally associated with WPAI scores at baseline, but predicted worse work impairment and activity impairment at year 1. The Beliefs about Medicines Questionnaire subscale with concerns about medicines at baseline independently predicted worse overall work impairment and worse activity impairment at year 1. In patients with gout who were intensively treated to the sUA target, work productivity and activity impairment were largely unchanged and at 1 year predicted by comorbidities and patient concerns about medication.

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.

Odds of Achieving Target Serum Uric Acid Levels Among Gout Patients: The Role of Rurality in Outcomes and Treatment Adherence.

The goal of this paper was to analyze patient outcomes related to gout treatment including, serum uric acid (sUA) measures and treatment adherence across patients in metropolitan, micropolitan or rural counties. We conducted a drug-disease cohort study among patients with gout initiating urate lowering therapy. The proportion of patients with sUA < 6 mg/dL at 1 year of follow-up is compared over the cohort groups using a chi-square test and adjusted logistic regression. Adherence to urate lowering therapy was calculated using the proportion of days covered (PDC). A T-test was used to compare the average PDC and an adjusted logistic regression model was used to estimate the odds of a PDC greater than 80%. A total of 9922 patients were included in the study. Most patients were in a metropolitan (77.4%) area, followed by micropolitan (11.8%) and finally, (10.8%) in a rural area. We found no statistically significant difference among the proportion of patients achieving target sUA of <6 mg/dL, 37.17% among metropolitan patients, 38.9% among micropolitan patients, and 37.7% for those in a rural area, P-value = .502. The proportion of patients achieving 80% treatment adherence was 49.92% in the metropolitan, 51.78% in the micropolitan, and 55.05% in the rural areas, P-value = .005. Adjusted regression models showed no statistically significant difference in proportions achieving target sUA levels or 80% adherence. Urban patients treated for gout did not have better gout outcomes compared to rural patients. Future research should consider provider-based interventions to improve outcomes.

Achievement of serum uric acid target by rheumatology clinic pharmacists compared with primary care providers in patients with gout

BackgroundThe American College of Rheumatology strongly recommends a treat-to-target management strategy to achieve and maintain serum uric acid (sUA) less than 6 mg/dL to decrease risk of gouty flare recurrence and permanent joint damage. ObjectiveTo compare the effectiveness of rheumatology clinic pharmacists and primary care providers (PCPs) in achieving a target sUA goal in patients with gout. MethodsThis retrospective chart review included patients aged 18 years and older starting urate-lowering therapy (ULT) (allopurinol, febuxostat, or probenecid) for gout between January 1, 2015, and December 31, 2019. Exclusion criteria were ULT use within the previous 6 months, baseline sUA less than 6 mg/dL, and death within 12 months of starting ULT. From ULT initiation, data were collected until sUA less than 6 mg/dL was achieved or a maximum of 12 months. The primary outcome was the percentage of patients who achieved sUA less than 6 mg/dL. Key secondary outcomes were percent reduction in sUA and time to sUA target achievement. ResultsOf 62 patients included in each group, 75.8% of patients in the pharmacist cohort versus 30.6% of patients in the PCP cohort achieved target sUA less than 6 mg/dL (odds ratio 7.09, 95% confidence interval 3.28–16.11, P < 0.001). Patients in the pharmacist-managed group also achieved a greater reduction in mean sUA (−36.7% vs. −26.9% respectively, P = 0.001). Among patients achieving target sUA, median time to target was similar at 92 and 86 days, respectively, despite significantly lower initial mean allopurinol doses in the pharmacist-managed group (102 mg/d vs. 145 mg/d, P < 0.001). ConclusionThe odds of achieving target sUA within 12 months were 7 times higher if gout was managed by a rheumatology clinic pharmacist as compared with a PCP. This study suggests the need for prescriber education and supports expansion of pharmacist-led gout management to primary care settings.

The Role of Ultrasound in Evaluating the Effect of Urate-lowering Drugs in Gout Patients.

Gout is one of the most common inflammatory arthritis, where identification of MSU crystals in synovial fluid is a widely used diagnostic measure. Ultrasonography has a great sensitivity in detecting signs of MSU deposits, such as tophi and double contour (DC), as mentioned in the latest gout criteria, allowing early clinical diagnosis and therapy. The objective of this study was to evaluate the changes in ultrasound of gout patients' knee and 1st metatarsophalangeal joint (MTP1) after initiation of urate-lowering therapy (ULT) drugs in the six-month period. Forty-three patients, fulfilling the ACR/EULAR 2015 criteria of gout with a score of >8, were enrolled; they were in between attacks and not on ULT for the last 6 months, or SUA concentration (SUA) of >6.0 mg/dL. Full examination, evaluation of joints pain by visual analog scale (VAS), ultrasonography (US) for tophus and DC at the knee, and MTP1 were performed at baseline and at 3 and 6 months (M3, M6) after starting ULT. After 6 months of treatment, patients reached the target SUA level showed higher disappearance of DC sign (p<0.05) and a decrease in tophus size (p<0.05). The percentage of tophus size at 6th month was 26.4% and 3% for DC sign disappearance, which was more at MTP1. Ultrasound examination in screening for gout tophi or DC sign before starting ULT and during follow-up is important and complements clinical examination.

Effect of metformin use on clinical outcomes and serum urate in gout patients with diabetes mellitus: a retrospective cohort study

ObjectiveGout and diabetes mellitus type 2 (DM) frequently co-exist. The pharmacological effects of metformin may include anti-inflammatory and urate lowering effects. The objective of this study was to test these effects in patients with gout starting uric acid lowering treatment (ULT) in secondary care.MethodsRetrospective cohort study including patients with gout and DM starting ULT. Differences in the incidence density of gout flares, proportion of patients reaching target sUA in the first six months after starting ULT, and difference in mean allopurinol dose at sUA target were compared between users of metformin and users of other or no anti-diabetic drugs (control group). Correction for confounding was applied.ResultsA total of 307 patients were included, of whom 160 (52.1%) used metformin. The incidence of flares was 1.61 and 1.70 in the first six months for respectively the metformin group and control group. The incidence rate ratio for gout flares was not significant (0.95, 95% CI 0.78 to 1.14). At six months, 62.8% and 54.9% reached target sUA in the metformin and control group respectively, corrected odds ratio of 1.09 (95% CI 0.66 to 1.80). There was no difference in mean allopurinol dose at sUA target 266 mg for metformin users and 236 mg for the control group, difference 30 mg (95% CI − 4.7 to 65.5).ConclusionsIn conclusion we could not confirm a clinically relevant anti-inflammatory or urate lowering effect of metformin in patients starting ULT treatment and receiving usual care flare prophylaxis.

Is Renoprotection Real for Patients with Hyperuricemia?

Number of patients with progressive chronic kidney disease (CKD) is increasing all over the world. One of the risk factors for CKD development and progression is increased serum uric acid (sUA) level. Possibly, control of hyperurcemia with urate lowering therapy drugs can slow the decline in kidney function. The objective: to determine efficacy and safety of allopurinol and febuxostat in treatment of patients with CKD and hyperurcemia to reduce the sUA level and analyze its influence on glomerular filtration rate (GFR). Materials and methods. The study included 45 CKD patients (stages 3b-5) without other severe/decompensated diseases and contraindications to the allopurinol/febuxostat. All patients underwent a comprehensive clinical and laboratory examination, and were divided into the study groups: Group I (28 patients, 61.3±3.2 y.o., CKD3b-12, CKD4-10, on hemodialysis-6 patients) received febuxostat, Group II (24 patients, 60.7Ѓ}4.1 y.o., CKD3b-9, CKD4-10, on hemodialysis – 5 patients) took allopurinol. Results. Achievement of the target level of sUA was significantly often registered in Group I: after 1 month – in 45.5% (in group II – in 15.9%, p&lt;0.001); after 3 months – in 67.5% (in group II – 21.2% p&lt;0.01); after 6 months, these figures were 90% and 37.1%, respectively (p&lt;0.01). sUA level &lt;300 μmol/l was accompanied by significant positive GFR changes in group I patients; in group II there was a gradual progression of GFR deterioration in 31.8% of patients. Conclusions. In patients with pre-dialysis stages of CKD febuxostat demonstrates renoprotective abilities. Use of febuxostat in patients with CKD stage 3b-4 and in patients on hemodialysis is safe and more effective for target sUA level achievement than the use of allopurinol.

Comparative efficacy and safety of topiroxostat at different dosages in hyperuricemic patients with or without gout: A network meta-analysis of randomized controlled trials.

We aimed to assess the relative efficacy and safety of topiroxostat at different dosages in hyperuricemic patients with or without gout. A Bayesian network meta-analysis was performed to combine direct and indirect evidence from randomized controlled trials (RCTs) for evaluating the efficacy and safety of topiroxostat at different dosages, allopurinol 200mg, and placebo in hyperuricemic patients with or without gout. Five RCTs, including 733 patients, fulfilled the inclusion criteria. The number of patients who had achieved a target serum uric acid (sUA) level was significantly higher in the topiroxostat 200mg group than in the placebo group (odds ratio, 1,023; 95% credible interval, 157.7-26,260). Similarly, the number of patients who had achieved the target sUA level was significantly higher with topiroxostat at other dosages and allopurinol than with placebo. The ranking probability based on the surface under the cumulative ranking curve indicated that topiroxostat 200mg was more likely to achieve the best target sUA level, followed by topiroxostat 80mg, allopurinol 200mg, topiroxostat 120mg, topiroxostat 160mg, topiroxostat 60mg, topiroxostat 40mg, and placebo. The frequency of adverse events (AEs) in the placebo group was lower than that in the topiroxostat 40mg, topiroxostat 60mg, and topiroxostat 200mg groups. Topiroxostat 200mg was the most effective treatment option for hyperuricemic patients with or without gout, with an increased risk of AEs.

Comparative efficacy and safety ofdotinurad, febuxostat, and benzbromarone in hyperuricemic patients with or without gout: Anetwork meta-analysis of randomized controlled trials.

We aimed to assess the relative efficacy and safety of dotinurad (2 mg), benzbromarone (50 mg), and febuxostat (40 mg) in hyperuricemic patients with or without gout. A Bayesian network meta-analysis was performed to combine direct and indirect evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of dotinurad (2 mg), benzbromarone (50mg), febuxostat (40 mg), and placebo in hyperuricemic patients with or without gout. Four RCTs, including 516 patients, fulfilled the inclusion criteria. The number of patients who achieved the target serum uric acid (sUA) level was significantly higher in the febuxostat 40-mg group than in the placebo group (OR 660.50, 95% credible interval (CrI) 75.47-19,584.80). The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that febuxostat 40 mg was more likely to achieve the best target sUA level (SUCRA = 0.849), followed by dotinurad 2 mg (SUCRA = 0.651), benzbromarone 50 mg (SUCRA = 0.501), and placebo (SUCRA < 0.001). The frequency of adverse drug reactions in the dotinurad 2-mg group, and in the benzbromarone 50-mg group tended to be lower than in the febuxostat 40-mg group. Febuxostat 40 mg and dotinurad 2 mg tended to be more effective than benzbromarone 50 mg, while dotinurad 2 mg and benzbromarone 50 mg tended to be safer than febuxostat 40 mg in hyperuricemic patients with or without gout.

Safety and efficacy of SHR4640 combined with febuxostat for primary hyperuricemia: a multicenter, randomized, double-blind, phase II study.

Background:To evaluate the safety, tolerability, and efficacy of SHR4640, a highly selective urate transporter-1 inhibitor, in combination with febuxostat, in patients with primary hyperuricemia.Methods:In this randomized, double-blind, parallel-controlled phase II study, patients whose fasting serum uric acid (sUA) levels were ⩾ 480 μmol/L at screening with gout or sUA levels were ⩾ 420 μmol/L lasting for at least 3 months without gout, either with sUA levels ⩾ 540 μmol/L at screening or sUA levels ⩾ 480 μmol/L with comorbidities at screening, were enrolled. Patients were randomized (1:1:1) to receive SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg orally once daily. The primary end point was the incidence of treatment-emergent adverse events (TEAEs).Results:A total of 93 patients were randomized and received treatment. TEAEs occurred in 55.9% of patients. The incidence of TEAEs was comparable among all the groups. Serious TEAEs occurred in one patient (1.1%), with no deaths observed. The proportion of patients who achieved the target sUA levels by week 4 was 79.3%, 96.6%, and 75.0% in the SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg groups, respectively. The mean percent reduction of sUA was 59.7%, 63.7%, and 41.8%, respectively.Conclusion:SHR4640 plus febuxostat exhibited a tolerable safety profile and substantial sUA lowering activity in patients with primary hyperuricemia.Registration:www.chinadrugtrials.org.cn; CTR 20192429

POSSIBILITIES OF RENOPROTECTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND HYPERURICEMIA.

The aim: To determine efficacy and safety of allopurinol and febuxostat in treatment of patients with CKD to reduce the sUA level and analyze its influence on glomerular filtration rate (GFR). Materials and methods: The study included 45 CKD patients (stages 3b-5) without other severe/decompensated diseases and contraindications to the allopurinol/febuxostat. All patients underwent a comprehensive clinical and laboratory examination, and were divided into the study groups: Group I (28 patients, 61,3±3,2 y.o., CKD3b-12, CKD4-10, on hemodialysis-6 patients) received febuxostat, Group II (24 patients, 60,7±4,1y.o., CKD3b-9, CKD4-10, on hemodialysis -5 patients) took allopurinol. Results: Achievement of the target level of sUA was significantly often registered in Group I: after 1 month - in 45.5% (in group II - in 15.9%, p<0.001); after 3 months - in 67.5% (in group II - 21.2% p<0.01); after 6 months, these figures were 90% and 37.1%, respectively (p<0.01). sUA level <300 μmol/l was accompanied by significant positive GFR changes in group I patients; in group II there was a gradual progression of GFR deterioration in 31.8% of patients. Conclusions: In patients with pre-dialysis stages of CKD febuxostat demonstrates renoprotective abilities. Use of febuxostat in patients with CKD stage 3b-4 and in patients on hemodialysis is safe and more effective for target sUA level achievement than the use of allopurinol.

Gender characteristics of gout and differences in response to taking xanthioxidase inhibitors

Introduction. To date, there is no consensus regarding the gender characteristics of the course of gout. There is little data on the possible difference between men and women in response to uric acid-lowering therapy.Aim. To compare the clinical characteristics of the course of gout and evaluate the differences in response to urate-lowering therapy (ULT) with allopurinol and febuxostat in men and women.Material and methods. The retrospective cohort study included 279 men and 83 women diagnosed with gout (ACR/EULAR, 2015). The comparative analysis of the clinical characteristics of gout, as well as responses to the intake of xanthioxidase (XO) inhibitors in representatives of different sexes, was carried out. We compared the gender characteristics of obtaining a positive response to ULT, defined as achieving a target serum uric acid (sUA) level of &lt; 360 μmol / l within 6 months of treatment, while taking allopurinol and febuxostat.Results. By the age at which the onset of gout took place, women were older than men, the duration of the disease in them was shorter. Men showed a shorter duration of the first attack of arthritis. Chronic arthritis was diagnosed in 56% of men and 35% of women (p &lt; 0.05). The process involved the joints of both the lower and upper extremities. However, more often the joints of the lower extremities were affected in men, and in the upper extremities in women. Tophus were detected in 35% of patients, of whom 30.3% were men, 4.7% were women (p &lt; 0.05). Allopurinol was prescribed to 216 men and 54 women, and febuxostat was prescribed to 63 men and 29 women. After six months, the proportion of women who achieved the target sUA was 57.5% and 65.8%, the proportion of men – 60.4% and 76.2% for allopurinol and febuxostat, respectively.Conclusion. The clinical manifestations of gout in men and women differ. Due to the pronounced increase in the level of uric acid, men develop more severe joint damage due to the tendency to chronicity. However, the study did not reveal gender differences in the response to XO inhibitors, which indicates that there is no need to choose therapy depending on the patient’s gender.

POS1140 RISK FACTORS FOR THE DEVELOPMENT OF DIABETES MELLITUS IN PATIENTS WITH GOUT ACCORDING TO A 6-YEAR PROSPECTIVE FOLLOW-UP STUDY

Background:Gout is often associated with diabetes mellitus (DM), but the role of serum uric acid (sUA) and urate-lowering drugs in its development in patients with gout remains controversial [1].Objectives:To study risk factors for DM in patients with gout based on the results of long-term prospective follow-up study.Methods:The prospective study included 444 patients with a crystal-verified diagnosis of gout, aged ≥18 years, 49 (11%) women, 395 (89%) men. Patients were followed up at the V.A. Nasonova Research Institute of Rheumatology from 2010 to January 2021, the median follow-up was 6.1 [2.8; 7.8] years. The exclusion criteria were the presence of other rheumatic diseases with symptoms of arthritis, DM. DM was diagnosed on the 1998 WHO criteria. The following parameters were considered as risk factors: gender, family history for diabetes mellitus, body mass index (BMI)&gt;25 kg/m2 and &gt; 30 kg/m2, waist volume ≥88 cm for women and ≥102 cm for men, alcohol consumption &gt; 20 units per week, chronic kidney disease (CKD), intake of diuretics and glucocorticoids, and serum total cholesterol &gt;5 mmol/l, triglycerides&gt;2.25 mmol/l, serum C-reactive protein (CRP) level&gt; 5 mg/l, as well as clinical manifestations of gout: subcutaneous tophi, polyarthritis (simultaneous involvement of ≥5 joints), intake of urate-lowering drugs, sUA (&gt; 480 μmol/L,&gt; 420 μmol/L,&gt; 360 μmol/L,&gt; 300 μmol/L). Statistica 12.0 package was used for statistical data processing.Results:A total of 444 patients were included, the mean age was 51.0±12.9 years, the median follow-up was 6.1 [2.8; 7.8] years. In dynamics: 35 (8%) patients died, 6 (1%) patients were not available, 403 patients were examined (44 (11%) - women and 359 (89%) - men). 290 (72%) patients received urate-lowering therapy (263 (65%) patients used allopurinol, 27 (7%) - febuxostat). The target sUA &lt;360 μmol/L was reached by 165 (41%) patients and &lt;300 μmol/L - by 92 (23%) patients. All patients with sUA&lt;300 μmol/L received urate-lowering therapy, 62 (67%) patients used allopurinol, 17 (18%) - febuxostat, 13 (14%) - uricosuric drugs. Diabetes mellitus was developed in 106 (26%) patients. The factors influencing the risk of developing diabetes were - the presence of diabetes in family history (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.37; 3.76); BMI&gt; 30 kg / m2 (OR 1.79, 95% CI 1.14; 2.80), diuretics (OR 2.32, 95% CI 1.36; 3.96) and sUA&gt; 300 μmol / l (OR 2.89, 95% CI 1.50, 5.56).Conclusion:The risk of developing DM in patients with gout is associated with sUA&gt; 300 μmol/l, which may be one of the probable reasons for choosing this as a target level. Large prospective studies are needed to confirm the antidiabetic effect of urate-lowering drugs.

Efficacy and Safety of Dotinurad in Hyperuricemic Patients With or Without Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

IntroductionA systematic review and meta-analysis of the available randomized controlled trials (RCTs) were conducted to investigate the efficacy and safety of dotinurad in hyperuricemic patients with or without gout. Dotinurad is a novel selective urate reabsorption inhibitor (SURI) that increases uric acid excretion by selectively inhibiting urate transporter 1 (URAT1). To the best of our knowledge, this is the first meta-analysis conducted to gauge the efficacy and safety of dotinurad. MethodsElectronic databases (PubMed, the Cochrane Library, and ClinicalTrials.gov) were searched from inception till March 2, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Randomized controlled trials comparing the efficacy and safety of dotinurad with placebo- or active (febuxostat or benzbromarone) control were included. The eligible studies were analyzed with RevMan 5.3 Software (The Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen).ResultsFour eligible studies, consisting of 684 hyperuricemic patients were included. The number of patients who achieved serum uric acid (sUA) levels ≤ 6.0 mg/dl favoured dotinurad 1 mg group as compared to placebo group (risk ratio {RR} = 39.27, 95% onfidence interval {CI}, 5.59 to 275.65; p = 0.0002), dotinurad 2 mg group compared with placebo group (RR = 45.36, 95% CI, 6.48 to 317.38; p= 0.0001), and dotinurad 4 mg group compared with placebo group (RR = 54.16, 95% CI, 7.76 to 377.77; p < 0.0001). Conversely, there was no significant difference in the number of patients who achieved the target sUA levels between dotinurad 2 mg and active control (RR = 1.00, 95% CI, 0.92 to 1.08; p = 0.91). Moreover, the percentage change in sUA levels from baseline to final visit favoured dotinurad 1 mg vs. placebo ((RR = 36.51, 95% CI, 33.00 to 40.02; p < 0.00001), dotinurad 2 mg vs. placebo (RR = 46.70, 95% CI, 42.53 to 50.87; p < 0.00001), and dotinurad 4 mg vs. placebo (RR = 63.84, 95% CI, 60.51 to 67.16; p < 0.00001), while no significant difference was seen in dotinurad 2 mg vs. active control (RR = -0.08, 95% CI, -4.27 to 4.11; p= 0.97). Compared with active or placebo control, dotinurad 2 mg showed no significant difference in the number of events of gouty arthritis (RR= 1.31, 95% CI, 0.47 to 3.71; p = 0.60), the number patients with adverse events (RR = 1.09, 95% CI, 0.91 to 1.30; p = 0.36), and the number of patients who experienced adverse drug reactions (RR = 1.00, 95% CI, 0.68 to 1.47; p = 0.99).ConclusionDotinurad shows significant improvement in serum uric acid levels in hyperuricemic individuals with or without gout. Its urate-lowering effect is comparable to the commonly available anti-hyperuricemic agents. Moreover, it is effective at doses 1 mg, 2 mg, and 4 mg and well-tolerated at a dose of 2 mg.