Effect of urate‐lowering therapy on the velocity of size reduction of tophi in chronic gout

Objective

The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout.

Method

Sixty‐three patients with crystal‐confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination.

Results

Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction.

Conclusion

Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single‐drug therapy.

     

Failure of rasburicase therapy in recurrent acute gout with tophi

Rasburicase, a recombinant urate oxidase enzyme, has been used successfully in several cases of chronic tophaceous gout. We report the case of an elderly woman with chronic tophaceous gout who failed rasburicase therapy due to recurrent acute episodes of gout following each rasburicase infusion, despite prophylactic therapy.     

Bullous tophi in gout.

Two gouty patients developed bullae containing massive numbers of monosodium urate crystals. Both patients had had treatment with systemic corticosteroids. A burn precipitated one bulla, showing that local tissue injury can be a factor in tophus localization.     

Combination urate-lowering therapy in the treatment of gout: What is the evidence?

Background

Combination therapy that includes a uricosuric and xanthine oxidase inhibitor (XOI) is recommended in guidelines for patients with gout who do not meet treatment targets with XOI monotherapy alone. While the use of combination therapies has been investigated for many years, we reviewed data from the published studies to investigate the efficacy and safety of this approach.

As compared to allopurinol, urate-lowering therapy with febuxostat has superior effects on oxidative stress and pulse wave velocity in patients with severe chronic tophaceous gout

We prospectively evaluated whether an effective 12-month uric acid-lowering therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and febuxostat in patients with chronic tophaceous gout has an impact on oxidative stress and/or vascular function. Patients with chronic tophaceous gout who did not receive active ULT were included. After clinical evaluation, serum uric acid levels (SUA) and markers of oxidative stress were measured, and carotid–femoral pulse wave velocity (cfPWV) was assessed. Patients were then treated with allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level ≤360 μmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and the cfPWV were measured again. Baseline characteristics of both groups showed no significant differences except a higher prevalence of moderate impairment of renal function (estimated glomerular filtration rate <60 ml/min) in the febuxostat group. Uric acid lowering with either inhibitors of XO resulted in almost equally effective reduction in SUA levels. The both treatment groups did not differ in their baseline cfPWV (allopurinol group: 14.1 ± 3.4 m/s, febuxostat group: 13.7 ± 2.7 m/s, p = 0.80). However, after 1 year of therapy, we observed a significant cfPWV increase in the allopurinol group (16.8 ± 4.3 m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3 ± 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA levels in patients with severe gout. However, we observed that febuxostat also appeared to be beneficial in preventing further arterial stiffening. Since cardiovascular events are an important issue in treating patients with gout, this unexpected finding may have important implications and should be further investigated in randomized controlled trials.     

Ultrasonographic measurement of tophi as an outcome measure for chronic gout

OBJECTIVE: To validate the usefulness of measuring tophi with ultrasonography (US) as an outcome measure for chronic tophaceous gout. METHODS: Patients with crystal-proven gout were included. To evaluate validity, intraarticular and articular deep tophi were evaluated with both magnetic resonance imaging (MRI) and US. Tophi were punctured with US guidance to evaluate face validity. Interobserver and intraobserver measurement studies were done to evaluate reliability, and to estimate the smallest detectable difference. Sensitivity to change was evaluated with a 12-month followup observational study of urate-lowering therapy. RESULTS: US detected at least one tophus in all joints where MRI found nodules considered to be tophi. There was a good correlation, but just fair agreement between measurements with US and MRI. Puncture of nodules suspected of being tophi recovered urate crystals in 83% of the procedures. Intraobserver intraclass correlation was > 0.90 for diameters and volume, while it was 0.71 to 0.83 in the interobserver study. US was found to be sensitive to change, and there was an inverse correlation between serum urate concentrations and change from baseline measurement of tophi. CONCLUSION: US measurement of tophi fulfilled the OMERACT filter for an outcome measure, although it should be tested further in randomized clinical trials.     

Prediction of renal and cardiometabolic outcomes in gout during urate-lowering therapy by sonography

Objectives

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).

Methods

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.

Results

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).

Conclusions

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.     

Prognostic factors associated with early gout flare recurrence in patients initiating urate-lowering therapy during an acute gout flare

Clinical Rheumatology - Lowering serum urate levels below the threshold for crystal formation with urate-lowering therapy (ULT) has been associated with a lower risk for gout flare reoccurrences....     

Risk factors of ultrasound-detected tophi in patients with gout

Clinical Rheumatology - Tophus is a characteristic manifestation of advanced gout, the clinical significance of which is often underestimated. This study aimed to compare the difference of clinical...     

Effect of urate-lowering therapy on renalfunction in chronic kidney disease stages 2-5 pa-tients with hyperuricemia

正Objective To investigate the effect of urate-lowering therapy on renal function in chroinc kidney disease(CKD) stages 2-5 patients with hyperuricemia(HUA). Methods A total of 132 patients of CKD stages2-5 with HUA between July 2016 and December 2017in Department of Nephrology of the Second Affiliated     

The clinical efficacy of urate-lowering therapy in acute gout: a meta-analysis of randomized controlled trials

Clinical Rheumatology - Gout is a common chronic disease with a high recurrence rate. To date, the debate continues about the best time for using urate lowering therapy (ULT) during an acute gout...     

Effect of urate-lowering therapy with febuxostat on oxidative stress in hyperuricemic patients with chronic kidney disease stages 3-5

<正>Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease(CKD) stages 3-5 patients with hyperuricemia(HUA).Methods The study was a prospective cohort study.The patients of CKD stages 3-5 with HUA be-     

Computed tomography of the knee joint as an indicator of intraarticular tophi in gout

Objective. To evaluate the utility of computed tomography (CT) of the knee joint for detecting intraarticular tophaceous deposits. Methods. A prospective study of 16 patients with gout affecting the knee was conducted. A condition for inclusion in the study was the presence of needle-shaped crystals with negative birefringence in the knee joint synovial fluid. Conventional radiography and CT were performed in each case. Results. Intraarticular opacities in the capsule and the synovium, consistent with the presence of tophaceous deposits, were found in 5 of the 16 patients (9 knee joints). The mean duration of gout was longer in the patients with intraarticular tophi than in those without tophi, and 2 of the patients with tophi had poor tolerance to antihyperuricemic therapy. Conclusion. Intraarticular opacities considered to represent tophi were observed in approximately one-third of the patients. The presence of tophi correlated with a longer duration of the disease and a poor tolerance to medication. We therefore suggest that CT of the knees could be useful in the assessment and followup of certain patients with gout.     

Analysis of risk factors for susceptibility of subcutaneous tophi in people with gout

正Objective To discuss the risk factors for susceptibility of subcutaneous tophi with an aim to provide clinical evidence for the prevention and treatment of tophi.Methods A total of 5 321 cases of gout patients whose course of disease was less than 10 years were selected and divided into two groups according to whether a subcutaneous tophus was present.The clinical information was collected and relevant biochemical indices were de-     

Modern differential-therapeutic aspects of the drug therapy of chronic gout

The present paper adopts a definite attitude to the differentiated therapy of the disturbances of the uric acid metabolism. This demands an exacter subdivision of the kind of the metabolic disturbance (types Ia, Ib, IIa, IIb, and III). On the basis of this classification in types an individually adapted therapy is possible. It might form the prerequisite of a still more effective meeting of the nephrogenic complications of the gout and of the reduction of the side effects of the necessary permanent therapy.