Addition of allopurinol to traditional Vietnamese medicine shows major improvement of 100 gout patients in a single center one-year prospective study.

BackgroundAccording to the 2012 ACR guidelines (1) anti-inflammatory prophylaxis is recommended when urate lowering drugs (ULDs) are initiated and should be continued if there is continuing gout activity and/or serum...

Rules of engagement: turning recommendations into results in the diagnosis and management of gout.

BackgroundLong term serum urate (SU) lowering to a target of <0.36 mmol/l (6 mg/dl) is recommended for effective gout management. However, many studies have reported low achievement of SU targets. The aim of this cross-sectional study was to examine the clinical and psychological factors associated with SU targets in patients with gout.MethodsPatients with gout for <10 years were recruited from primary and secondary care settings. SU target was defined as SU concentration <0.36 mmol/L at the time of the study visit. Both clinical and psychological factors associated with SU target were analysed. The relationship between SU target and measures of gout activity such as flare frequency, tophi, work absences, and Health Assessment Questionnaire-II was also analysed.ResultsOf the 273 patients enrolled into the study, 89 (32.6%) had SU concentration <0.36 mmol/L. Urate-lowering therapy (ULT) use was strongly associated with SU target (p < 0.001). In those patients prescribed ULT (n = 181), allopurinol dose, patient confidence to keep SU under control, female sex, and ethnicity were independently associated with SU target. Other patient psychological measures and health-related behaviours, including adherence scores, were not independently associated with SU target in those taking ULT. Creatinine clearance, diuretic use, age, and body mass index were not associated with SU target. Patients at SU target reported lower gout flare frequency, compared with those not at target (p = 0.03).ConclusionsULT prescription and dosing are key modifiable factors associated with achieving SU target. These data support interventions focusing on improved use of ULT to optimise outcomes in patients with gout.

Association between serum urate and flares in people with gout and evidence for surrogate status: a secondary analysis of two randomised controlled trials.

To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout. We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points. Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups. Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout.

To assess whether the extent of monosodium urate (MSU) crystal deposition estimated by ultrasound could predict renal and cardiometabolic events during urate-lowering therapy (ULT). A prospective study on gout patients from two referral centers initiating ULT who underwent baseline ultrasound and were followed for 1 year. Ultrasound scans assessed six joints for double-contour (DC) signs and tophi. A five-point change (mL/min/1.73 m2 ) in the glomerular filtration rate at month 12 (M12) was considered significant. Outcomes of interest were renal function degraded versus improved and a composite cardiometabolic outcome (new hypertension, diabetes, atherosclerotic disease, and cardiovascular death). Homogeneity analyses and Cox regression models were performed. One hundred sixty patients were recruited. At baseline, 81.1% of patients (n = 129) showed sonographic tophi with a mean number of 1.4 joints (±1.3) with a DC sign. At M12, 18 patients (11.3%) were lost to follow-up. The serum urate (SU) target (<6.0 mg/dL) was reached in 86 patients (69.9%). Regarding renal function, 15.9% of patients showed improvement, while in 31.0% it degraded. Fourteen new cardiometabolic events occurred in 12 patients. Neither the DC sign nor tophi showed any significant impact on the outcomes of interest. Baseline SU level was higher in those with renal improvement but not with renal decline, while achieving the SU target protected against new cardiometabolic events (HR = 0.2; 95% CI: 0.05-0.81). Sonographic MSU crystal burden was unhelpful in predicting renal and cardiometabolic events during the first year of ULT. Reaching the SU target prevented cardiometabolic events, while its benefit in preserving/improving renal function is unclear.

BackgroundDiuretics have been associated with impaired response and refractoriness in gout, but whether this effect is still present with new urate-lowering drugs (ULD) and treat-to-target strategies is unknown. The aim of the present study was to assess the impact of the diuretics on the response to ULD in patients with gout. MethodsThis was a retrospective analysis of an inception cohort. Participants were classified according to the type of ULD prescribed. We analysed the maximal dose of ULD (primary outcome variable), serum urate (SU) reduction, and the achievement of different SU targets (6 mg/dL, 5 mg/dL, and 4 mg/dL), according to the type of ULD prescribed and use of diuretics (loop and/or thiazide). We adjusted for confounders using multiple linear regression analysis.ResultsWe included 245 patients: 208 treated with allopurinol (66 on diuretics, 31.7%), 35 with febuxostat (19 on diuretics, 57.6%), and 2 with benzbromarone. Significantly fewer participants in the allopurinol plus diuretics subgroup achieved SU levels of less than 5 mg/dL, but we found no other significant differences in SU targets associated with diuretics. Regarding the maximum ULD dose, a simple linear regression suggested an inverse relationship with diuretics (beta = − 0.125, p = 0.073), but this did not hold in the multivariable analysis (beta = − 0.47, p = 0.833). There was no association with febuxostat (beta = − 0.116, p = 0.514).ConclusionDiuretics do not appear to have a significant impact on managing gout.

A gout attack may evolve after a purine-rich diet or alcohol and after starting urate-lowering therapy (ULT). The relationships between fluctuation and change in serum urate (SU) with the occurrence of flares were investigated in this study. In the prospective NOR-Gout study, gout patients with increased SU and a recent flare were treated to target with ULT over 1 year, with follow-up at year 2 with SU and flare as outcomes. SU and flares were assessed at both monthly and 3-monthly intervals until target SU was reached. Fluctuation over periods and changes in SU between two time points were assessed and compared in patients with and without flares. At year 1, 186 patients completed follow-up (88.2%) and 173 (82.0%) at year 2. Mean age (SD) at baseline was 56.4 (13.7) years, disease duration was 7.8 (7.6) years, and 95.3% were men. The first-year SU fluctuation and change were related to flare occurrence during year 1 (both p < 0.05). High fluctuation with an absolute sum of all SU changes during the first 9 months was related to flares over 3-month periods (all p < 0.05), and high fluctuation during the first 3 months was related to flares in months 3–6 (p = 0.04). Monthly and high SU changes or again reaching higher SU levels > 360 µmol/l were not related to flares. Fluctuation and change in SU were related to flare occurrence during the first year of ULT, while changes between visits and reaching SU levels > 360 µmol/L were not related to flares.Key Points• Urate-lowering therapy seeks to achieve a treatment target and prevent gout flares, and changes in serum urate are related to gout flares.• Fluctuation and changes in serum urate were associated with gout flares, suggesting that fluctuation in serum urate is unfavourable during gout treatment.• During urate-lowering therapy in gout in clinical practice, fluctuation of serum urate, for example, due to lack of adherence, should be observed and avoided.

BackgroundDespite its high prevalence and availability of effective treatments, recent reports have shown that gout is often poorly managed. New drugs and new evidence concerning the use of established treatments...

The European League Against Rheumatism published updated recommendations for the management of gout in 2016, comprising 3 overarching principles and 11 key recommendations for clinical practice. Patient education about the pathophysiology of gout and its comorbidities, as well as the existence of effective treatments are important, and understanding the principles of managing acute attacks and eliminating urate crystals by lifelong lowering of the serum urate (SU) below a target level are essential. Advice about lifestyle, diet, weight, and other risk factors, as well as the need to screen for, and manage, comorbidities is emphasized. For the treatment of flares, colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and oral or intraarticular steroids, or a combination thereof, are recommended. In patients with frequent flares and contraindications to colchicine, NSAIDs, and corticosteroids, an interleukin-1 blocker should be considered. Urate-lowering therapy (ULT) should be discussed from the first presentation of the disease, and SU levels should be maintained at less than 6 mg/dl (360 µmol/l), or less than 5 mg/dl (300 µmol/l) in patients with severe gout. Allopurinol is recommended as first-line ULT with dose adjustment according to renal function. If the SU target cannot be achieved with allopurinol, then febuxostat, a uricosuric, or combining a xanthine oxidase inhibitor with a uricosuric should be considered. All ULTs should be started at low dose and titrated upwards until the SU target is achieved. Unless contraindicated, flare prophylaxis with low-dose colchicine or with NSAIDs at low dosage is recommended during the first 6 months of ULT. In patients with refractory gout, pegloticase can be considered.

ObjectivesTo determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.MethodsPeople, including those with chronic kidney disease, who completed the first...

Urate and oxypurinol, allopurinol’s active metabolite, are predominantly eliminated by the kidneys. Therefore, optimising allopurinol dosing in patients on dialysis is challenging. This review explores allopurinol dosing practices, oxypurinol pharmacokinetics, and effectiveness in gout patients receiving haemodialysis or peritoneal dialysis (PD). Five databases and grey literature were searched. Studies on gout patients on allopurinol, receiving dialysis, and reporting dosing, pharmacokinetics, or effectiveness (reduction in urate and/or gout flares) were included. , full text screening and data extraction were done by two authors. Studies were grouped by dialysis modality. Eighteen studies were identified including 390 patients, most (n = 274, 70%) on haemodialysis with allopurinol administered after dialysis. The peritoneal dialytic clearance of oxypurinol (3.14 mL/min, n = 5) and urate (2.7–4 mL/min, n = 25) was similar. The haemodialytic clearance was 78–137 mL/min for oxypurinol (n = 21) and 80–165 mL/min for urate (n = 19). Allopurinol doses were higher in haemodialysis (100–600 mg/day) than PD (110–125 mg/day). Haemodialysis sessions decreased oxypurinol and urate concentrations by 39–57% (n = 30) and 56–71% (n = 6), respectively. Over time (1–230 days), urate concentrations in haemodialysis (n = 85) reduced by 14–41%. Target serum urate (< 0.36 mmol/L) was achieved in 61% (20/33) and 47% (13/28) of haemodialysis and PD patients, respectively. Gout flares decreased from 2 to 0.1 attacks/year in patients receiving dialysis (n = 79). Oxypurinol and urate clearance by haemodialysis was higher than PD, necessitating higher doses of allopurinol. POST dialysis allopurinol doses titrated to target urate are suggested. Future studies considering the impact of dialysis modality on allopurinol dose requirements are needed.Graphical abstract

Determine the proportion of patients achieving target serum urate (SU), defined as < 6 mg/dl for patients with non-severe gout and < 5 mg/dl for patients with severe gout, as well as the proportion of patients achieving remission after 5 years of followup. Patients from the Gout Study Group (GRESGO) cohort were evaluated at 6-month intervals. Demographic and clinical data were obtained at baseline. Visits included assessments of serum urate, flares, tophus burden, health-related quality of life using the EQ-5D, activity limitations using the Health Assessment Questionnaire adapted for gout, and pain level and patient's global assessment using visual analog scales. Treatment for gout and associated diseases was prescribed according to guidelines and available drugs. Of 500 patients studied, 221 had severe gout (44%) and 279 had non-severe gout (56%) at baseline. No significant differences were observed across the study in percentages of severe gout versus non-severe gout patients achieving SU 6 mg/dl or 5 mg/dl. The highest proportion of patients achieving target SU (50-70%) and remission (39%) were found after 3-4 years of followup. In the fifth year, these proportions decreased and 28% of the patients were in remission, but only 40 patients remained in the study. None of the patients with severe gout achieved remission. In patients with severe gout, target SU was hard to achieve and remission was not possible. The main obstacles for target SU and gout remission include poor medication adherence, persistent tophi, and loss to followup.

Despite effective treatment, gout is poorly managed. The aim of this study was to determine rates of serum urate (SU) testing and allopurinol dose adjustment in patients admitted to Christchurch-based hospitals who were receiving allopurinol. The hospital electronic prescribing and administration (ePA) system was used to identify patients receiving allopurinol during hospital admissions from March 2016 to March 2023. Demographics, SU, renal function, and changes to allopurinol therapy were recorded for each admission. Results were stratified by target SU and renal function. Of 18,081 patients who received allopurinol, SU was measured in 2950 (16.32%). The mean SU was 0.37 (SD 0.12) mmol/L, with 1270 (43.05%) above target SU (0.36 mmol/L). Admissions with chronic kidney disease (CKD) stage 3-5 were more likely to have SU above target than those with CKD stage 1-2 (78.84% vs 21.26%; P < 0.001). Among those with SU above target, allopurinol was discontinued in 148 (11.65%) and the dose reduced in 44 (3.46%), increased in 92 (7.24%), and unchanged in 986 (77.63%) during the admission. Those above target SU with CKD stage 3-5 were more likely to stop or decrease allopurinol compared to those with CKD stage 1-2 (16.4% vs 10.4%; P = 0.01). More than 80% of hospital admissions did not have SU measured, despite the patient receiving allopurinol. Most admissions had suboptimal management of the allopurinol dose in the context of their SU. These results reflect a missed opportunity to review and optimize gout management.

Hitting the target in gout.