Switching from allopurinol to febuxostat for the treatment of hyperuricemia and renal function in patients with chronic kidney disease

Hyperuricemia is a frequent complication of chronic kidney disease (CKD). Febuxostat is a novel xanthine oxidase inhibitor that is metabolized by many metabolic pathways in the kidney and the liver. We performed a 1-year cohort study of 73 hyperuricemic patients who had an estimated glomerular filtration rate (eGFR) below 45 ml/min and were being treated with urate-lowering therapy. In 51 patients, treatment was changed from allopurinol to febuxostat, and the other 22 patients were continued on allopurinol. The serum levels of uric acid (UA) level, creatinine, and other biochemical parameters were measured at baseline and after 3, 6, 9, and 12 months of treatment. The serum UA levels significantly decreased from 6.1?±?1.0 to 5.7?±?1.2 mg/dl in the febuxostat group and significantly increased from 6.2?±?1.1 to 6.6?±?1.1 mg/dl in the allopurinol group. The eGFR decreased 27.3 to 25.7 ml/min in the febuxostat group and from 26.1 to 19.9 ml/min in the allopurinol group. The switch from allopurinol to febuxostat was significantly associated with the changes in eGFR according to a multiple regression analysis (β?=??0.22145, P?相似文献   

Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: A 28‐week,phase III,randomized, double‐blind,parallel‐group trial

Objective

To compare the urate‐lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.

Methods

Subjects (n = 1,072) with hyperuricemia (serum urate level ≥8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to ≤2.0 mg/dl) renal function were randomized to receive once‐daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.

Results

Significantly (P ≤ 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.

Conclusion

At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.     

Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol

Objective

To compare the characteristics of female versus male gout patients and assess urate‐lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout.

Methods

This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level ≥8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function). Baseline demographics and characteristics were summarized and compared between female and male subjects. Urate‐lowering efficacy, which was defined as the proportion of subjects with sUA levels <6.0 mg/dl at final visit, was assessed for all subjects and, among women, according to baseline renal function.

Results

Female gout subjects (n = 226) were older with significantly higher rates of obesity and metabolic and cardiovascular comorbidities than their male counterparts. The percentage of female subjects with sUA levels <6.0 mg/dl at final visit was 0% in the placebo group, 54.3%, 85.1%, 81.0%, and 100.0% in the febuxostat 40 mg, 80 mg, 120 mg, and 240 mg groups, respectively, and 45.9% in the allopurinol group. Similar patterns of urate‐lowering efficacy rates were observed when stratified by renal function. Among all the female subjects, febuxostat 80 mg was significantly more efficacious than allopurinol (P < 0.001). Rates of adverse events (AEs) were low. The most frequently reported AEs were upper respiratory tract infections, musculoskeletal/connective tissue disorders, and diarrhea.

Conclusion

These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities.     

Effects of azelnidipine on uric acid metabolism in patients with essential hypertension

Purpose: To examine effects of a long-acting calcium channel blocker (CCB) azelnidipine on uric acid metabolism in hypertensive patients.

Methods: Azelnidipine was administered to 72 patients at a daily dose of 8?mg or 16?mg. In 22 cases out of the 72 patients, a different CCB was switched to azelnidipine. Blood pressure was measured and biochemical parameters of blood and urine were evaluated before and 2–3 months after the administration.

Results: Azelnidipine significantly decreased both systolic and diastolic blood pressure and the heart rate. It decreased both serum urate levels and the urinary uric acid to creatinine ratio (Uur/Ucr), but did not affect the uric acid clearance to creatinine clearance ratio (Cur/Ccr). Azelnidipine decreased both Uur/Ucr and Cur/Ccr in patients with Uur/Ucr ≥0.5 or ≥0.34, although it did not change these clearance parameters in patients with Uur/Ucr <0.5 or <0.34. Azelnidipine decreased the serum urate levels and Uur/Ucr in hyperuricemic patients with uric acid levels ≥7.0?mg/dL in males and ≥6.0?mg/dL in females. It did not change these parameters in normouricemic patients with serum urate levels <7.0?mg/dL in males and <6.0?mg/dL in females. Azelnidipine decreased Uur/Ucr and Cur/Ccr in hyperuricemic patients with normal or overexcretion of uric acid, although it did not change these clearance parameters in hyperuricemic patients with uric acid hypoexcretion.

Conclusions: Azelnidipine decreased the serum urate acid levels and Uur/Ucr, and this response was most prominent in hyperuricemic patients or patients with normal and overexcretion of uric acid.     

Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout

OBJECTIVES—To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout.
METHODS—Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl).
RESULTS—Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal fuction improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day.
CONCLUSION—Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.

Keywords: gout; gout suppressants; allopurinol; benzbromarone     

A systematic review and meta-analysis on the safety and efficacy of febuxostat versus allopurinol in chronic gout

Objective

To evaluate the safety and efficacy of febuxostat compared to allopurinol for the treatment of chronic gout.

Methods

We did a systematic review and meta-analysis of randomized and non-randomized controlled trials that compared oral febuxostat to oral allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios (RR) were calculated with random effects and were reported with corresponding 95% confidence intervals (CI).

Results

From 1076 potentially relevant citations, 7 studies and 25 associated publications met inclusion criteria; 5 studies were ultimately included in the analysis. Febuxostat did not reduce the risk of gout flares compared with allopurinol (RR = 1.16, 95% CI = 1.03–1.30, I² = 44%). Overall, the risk of any adverse event was lower in febuxostat recipients compared to allopurinol (RR = 0.94, 95% CI = 0.90–0.99, I² = 13%). Patients receiving febuxostat were more likely to achieve a serum uric acid of <6 mg/dl than allopurinol recipients (RR = 1.56, 95% CI = 1.22–2.00, I² = 92%). Subgroup analysis did not indicate any significant difference between high- and low-dose febuxostat on the risk of gout flares.

Conclusion

Although febuxostat was associated with higher likelihood of achieving a target serum uric acid level of <6 mg/dl, there was significant heterogeneity in the pooled results. There was no evidence that febuxostat is superior to allopurinol for clinically relevant outcomes. Given its higher cost, febuxostat should not be routinely used for chronic gout.     

Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase: A twenty‐eight–day,multicenter, phase II,randomized, double‐blind,placebo‐controlled,dose‐response clinical trial examining safety and efficacy in patients with gout

Objective

Gout affects ∼1–2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (≥8.0 mg/dl).

Methods

We conducted a phase II, randomized, double‐blind, placebo‐controlled trial in 153 patients (ages 23–80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28.

Results

Greater proportions of febuxostat‐treated patients than placebo‐treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40‐mg, 44% in the 80‐mg, and 59% in the 120‐mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40‐mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8–13%). Incidences of treatment‐related adverse events were similar in the febuxostat and placebo groups.

Conclusion

Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.

     

Temporal evolution of urate crystal deposition over articular cartilage after successful urate-lowering therapy in patients with gout: An ultrasonographic perspective

Objective: To detect evolution of ultrasonographic signs of deposition of monosodium urate crystals (MSUC) in gouty joints by serial ultrasonography after initiation of urate-lowering therapy (ULT).

Methods: Adult gout patients were examined by serial ultrasonography after initiation of ULT with target serum uric acid (SUA) Results: Thirty-eight male patients with gout with mean age of 50?±?11?years, median disease duration of 48 months and baseline mean SUA level of 8.8?±?1.5?mg/dL were recruited. Ultrasonographic evidence of MSUC deposition was detected in 89.74% of first metatarsophalangeal (MTP) joints and 27.63% of knee joints. Double contour sign (DCS), tophi, and hyperechoic spots (HES) were detected in 77.63%, 43.42%, and 19.74% of first MTPs, respectively. SUA level normalizes and plateaus after fourth month of follow-up. DCS thickness reduced significantly throughout the follow-up period. Overall, 86.25% DCS and 100% HES disappeared with median time of 6 months and 5.7 months, respectively. SUA normalization was the only significant predictor of DCS disappearance.

Conclusions: Serial ultrasonographic determination of DCS, tophi, or HES during hypouricemic therapy is a noninvasive, effective method to detect the lowering of burden of urate load in gouty joints.     

Clinical efficacy and safety of topiroxostat in Japanese hyperuricemic patients with or without gout: a randomized,double-blinded,controlled phase 2b study

Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used in Japan for the treatment of hyperuricemic patients with or without gout. In terms of the effectiveness of topiroxostat in lowering serum urate levels, the dose–response relationship has been evaluated; however, it remains to be verified. A randomized, multi-center, double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout. During the 16-week study, 157 Japanese hyperuricemic patients with or without gout were randomly assigned to receive a placebo, topiroxostat at 120 or 160 mg/day, or allopurinol at 200 mg/day. The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration. A dose–response relationship (regarding decreases in the serum urate levels) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day. Moreover, at the end of administration, the lowering rate of serum urate levels was determined to be ?44.8% in the topiroxostat 160-mg/day group. No significant difference in the incidence of adverse events was observed among all groups, including the allopurinol group. The serum urate-lowering effect of topiroxostat was found to have a dose–response relationship in Japanese hyperuricemic patients with or without gout.     

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout

OBJECTIVE: Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl). METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28. RESULTS: Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups. CONCLUSION: Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.     

Predicting Response or Non-response to Urate-Lowering Therapy in Patients with Gout

Purpose of Review

To review the extent of treatment success or failure with the xanthine oxidoreductase inhibitors allopurinol and febuxostat and indicate how the dosage of urate-lowering therapy (ULT) may be modified to increase the response in the majority of patients with gout.

Recent Findings

Gout flares are associated with serum concentrations of urate above 0.42 mmol/L (7 mg/dL). Achieving and maintaining serum urate below 0.36 mmol/L is considered an effective response to ULT. On an intention to treat basis, clinical trials indicate that allopurinol at daily doses of 100 to 300 mg decreases serum urate adequately in only about 40% of gout patients while febuxostat 80 mg daily reduces serum urate adequately in approximately 70% of gout patients. Higher doses of ULT may be required in patients receiving concomitant diuretics. The addition of a uricosuric agent to allopurinol and febuxostat therapy significantly increases the proportion of patients achieving adequate lowering of serum urate. Finally, carriers of a genetic variant of the transporter, ABCG2 (BCRP), have a decreased response to allopurinol.

Summary

Careful examination of medication adherence, titration of doses, and the addition of uricosuric agents increase the percentage of patients responding to allopurinol and febuxostat.

     

Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients

Background Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Methods Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Results Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean?±?SD of hs-CRP among men and women were 2.85?±?2.84?mg/dl and 2.80?±?4.80?mg/dl (p?=?0.047) respectively. Mean?±?SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83?±?3.80?mg/dl, 3.52?±?5.1?mg/dl, 2.22?±?2.3?mg/dl and 5.3?±?5.04?mg/dl respectively. Relationship between hs-CRP and inflammation activities (p?p?p?Conclusion Although serum hs-CRP is not a specific biomarker for gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis.     

Prophylaxis of acute flares when initiating febuxostat for chronic gouty arthritis in a real-world clinical setting

Objective: Flare prophylaxis is recommended during urate-lowering therapy (ULT) despite lack of proven benefit especially when initiating febuxostat. We investigated if colchicine or steroids administration during initiation of febuxostat for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares.

Methods: Patients with confirmed diagnosis of gout starting febuxostat were retrospectively studied. Frequency, severity, and length of flares were analyzed. Assessment of severity based on a visual analog scale (VAS).

Results: Two hundred and seventy-three patients were studied. The mean dose of colchicine and steroids was 0.53?±?0.15?mg PO QD and 7.55?±?1.30?mg prednisone equivalent PO QD; while the duration was 6.13?±?1.14 and 6.20?±?1.36 months, respectively. Subjects treated with colchicine and steroids suffered fewer total flares (0.30, 0.96 vs 2.47, p?=?.000), fewer flares from 0 to 3 months (0.26, 0.71 vs 1.72, p?=?.000), less severe flares assessed by VAS than those without prophylactic therapy (3.65, 3.49 vs 5.54, p?=?.000). Both total flares (p?=?.003) and flares from 0 to 3 months (p?=?.008) of the colchicine group were fewer than the steroids group. There were no significant differences in length of flares among groups (p?=?.815). Both colchicine and steroids were well tolerated.

Conclusion: The use of colchicine or steroids prophylaxis reduces the frequency and severity of acute gout flares during initiation of febuxostat for chronic gouty arthritis. Colchicine is superior to steroids in flares prophylaxis. Prophylactic therapy with colchicine 0.5?mg PO QD or steroids 7.5?mg prednisone equivalent PO QD for 6 months is suggested.     

Efficacy of mizoribine treatment in patients with Sjögren’s syndrome: an open pilot trial

Abstract

The aim of this study was to evaluate the efficacy and safety of mizoribine in patients with Sjögren’s syndrome. Forty patients with sicca syndrome, whose conditions were definitely diagnosed as Sjögren’s syndrome, were given mizoribine orally at a dosage of 150?mg/day for 12 months. The percentage change in salivary secretion after 3, 6, and 12 months of the therapy increased to +112.2% (P < 0.001), +119.9% (P < 0.01), and +147.3% (P < 0.001), respectively, compared with the baseline. Serum IgG levels decreased significantly throughout the study, and the level was 1969.4 ± 620.0?mg/dl after treatment for 12 months compared with the pretreatment value of 2094.3 ± 746.6?mg/dl (P < 0.05). The patient’s assessment of clinical signs and symptoms on a 10-cm visual analog scale improved significantly from 7.2 ± 2.3?cm at the start of the treatment to 5.0 ± 1.9?cm after 12 months (P < 0.001). There was a similar improvement in the physician’s assessment using the 10-cm visual analog scale: 7.1 ± 1.6?cm at the start of the treatment and 5.2 ± 1.9?cm after 12 months (P < 0.001). With regard to safety, no serious adverse reactions were observed. Although a controlled study would be required to clarify the efficacy of mizoribine, these preliminary observations indicate its efficacy for ameliorating glandular symptoms through improvements in immune abnormalities in patients with Sjögren’s syndrome.     

Diabetes mellitus,serum urate and gout. A study in 314 patients

Summary The chemical similarity between urate and alloxan stimulated the measurement of serum urate in 314 diabetics. Only one patient had gout and none had a family history of gout. The mean serum urate level in males was 4.8 mg/100 ml (SD ± 1.57) whilst the mean value in females was 4.2 mg/100 ml (SD ± 1.59). Males had significantly higher levels than females (p<0.001). The levels in both sexes increased significantly with age. Seventeen of the 25 diabetics (68%) with serum urate levels above the ‘normal’ range were known to have blood urea levels of over 40 mg/100 ml. This study does not support the hypothesis of a significant relationship between gout, raised serum urate levels and diabetes mellitus. Traduzione a cura di G. U.     

Prevalence of monosodium urate deposits in a population of rheumatoid arthritis patients with hyperuricemia

ObjectivesTo investigate the prevalence of monosodium urate (MSU) crystal deposits, indicative for gout, in a population of rheumatoid arthritis (RA) patients with concomitant hyperuricemia and to analyze the clinical and disease-specific characteristics of RA patients who exhibit MSU crystal deposits.MethodsOverall, 100 consecutive patients with the diagnosis of RA and a serum urate level above 6 mg/dl underwent dual energy computed tomography (DECT) of both feet and hands to search for MSU crystals in a prospective study between October 2011 and July 2013. Presence and extent of MSU crystal deposits on DECT was assessed by automated volume measurement. Demographic and disease-specific characteristics were recorded and included into two logistic regression models to test for the factors associated with MSU crystal deposits in RA.ResultsHyperuricemic RA patients were mostly male (55%), over 60 years of age (63 ± 11 years), had established disease (8.7 ± 10.5 years) and a mean disease activity score 28 (DAS 28) of 3.2. In total, 20 out of 100 patients displayed MSU crystal deposits in DECT. Interestingly, the majority (70%) of the RA patients positive for MSU crystal deposits were seronegative RA patients. Hence, every third seronegative RA patient had MSU crystal deposits. According to logistic regression model analysis, seronegative status correlated positively with presence of urate deposits (p = 0.019).ConclusionsThese data show that a considerable number of RA patients display periarticular MSU crystal deposits. Seronegative patients were shown to be predominantly affected with every third patient being positive for urate deposits.     

Dyslipidemia,Alcohol Consumption,and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate‐Lowering Therapy

Objective

In real life, in a substantial proportion of gouty patients receiving urate‐lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT.

Methods

This cross‐sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well‐controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses.

Results

Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high‐density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26–0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29–2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11–2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15–2.00]; P = 0.003).

Conclusion

Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

     

Potential Dangers of Serum Urate-Lowering Therapy

In observational studies, high serum urate levels are associated with adverse outcomes, including mortality. However, the hypothesis that urate-lowering may improve nongout outcomes has not been confirmed by placebo-controlled clinical trials. On the contrary, 7 recent placebo-controlled trials of urate-lowering drugs with different mechanisms of action (uricosuric: lesinurad; xanthine oxidase inhibition: febuxostat; uricase: pegloticase) have observed higher mortality or trends to higher mortality in gout patients, with the largest decreases in serum urate. Because all urate-lowering mechanisms were implicated, this raises safety concerns about urate-lowering itself. Far from unexpected, the higher mortality associated with more intense urate-lowering is in line with the U-shaped association of urate with mortality in some observational studies. Urate accounts for most of the antioxidant capacity of plasma, and strategies to increase urate are undergoing clinical trials in neurological disease. Post hoc analysis of recent trials should explore whether the magnitude of urate-lowering is associated with adverse outcomes, and safety trials are needed before guidelines recommend lowering serum urate below certain thresholds.     

Hypoglycemic and hypolipidemic activity of Hibiscus rosa sinensis Linn on streptozotocin–induced diabetic rats

To investigate the hypoglycemic activity of an aqueous extract of the flower of Hibiscus rosa sinensis on blood glucose in normal and streptozotocin (STZ) -induced diabetic rats, serum triglyceride and cholesterol levels and the effect of the flower extract on insulin secretion. Effect of H. rosa sinensis flower extract on blood glucose was studied with fed, fasted and glucose-loaded diabetic and nondiabetic rats. Glycosylated hemoglobin, serum insulin levels and lipid profile were also determined. Student??s t test was used for statistical analysis. In normal rats, the aqueous extract of the flower of H. rosa sinensis (250 and 500?mg/kg body weight) significantly (P?<?0.001) reduced the blood glucose levels after an oral glucose load from 127.9?±?5.6 to 80.6?±?3.9?mg/dl 2?h after oral administration of the flower extract. It also significantly lowered the blood glucose in STZ diabetic rats from 241.0?±?6.6 to 90.8?±?5.7?mg/dl after 21?days of oral administration of the extract (P?<?0.001). Serum insulin levels were not stimulated in the animals treated with the extract. Glycosylated hemoglobin and serum lipid profiles were significantly lowered by the administration of the extract. From the studies, it can be concluded that the aqueous extract of the flowers of H. rosa sinensis at a dosage of 500?mg/kg/day exhibits significant hypoglycemic and hypolipidemic activities. A marked reduction in glycosylated hemoglobin was also observed while insulin levels did not show any significant change.