scholarly journals A single-centre experience of febuxostat as a second-line urate-lowering therapy

2021 ◽  
Vol 16 (1) ◽  
pp. 50-55
Author(s):  
Swee Gaik Ong ◽  
Hui Jen Ding

Introduction: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease. Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals. Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported. Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 282.1-282
Author(s):  
R. Flood ◽  
C. Kirby ◽  
Y. Alammari ◽  
D. Kane ◽  
R. Mullan

Background:Emerging evidence that the joints of asymptomatic hyperuricaemic individuals contain monosodium urate (MSU) deposits and that alternative presentations of foot pain occur in hyperuricaemia suggests that preclinical phases may occur prior to a first episodic gout attack. (1) This case–control study evaluates urate deposition in hyperuricaemic individuals not fulfilling the current gout classification criteria, as well as a potential therapeutic role for urate lowering therapy (ULT).Objectives:To investigate whether ULT reduces non-episodic foot pain in patients who fail to meet ACR/EULAR 2015 gout classification criteria.Methods:Following informed consent, hyperuricaemic individuals with persistent, non-episodic foot pain (n=53) not fulfilling ACR/EULAR 2015 gout classification criteria, were compared with asymptomatic hyperuricaemic controls (n=18). Ultrasound (US) of bilateral first metatarsophalangeal (MTP) joints and features of MSU deposition including double contour (DC) sign, tophus and juxta-articular erosion were recorded. Cases only were treated with febuxostat or allopurinol daily for 6 months. Serum urate, 24-hour and 7-day visual analogue score (VAS) 0–100 mm pain scales and the Manchester Foot Pain and Disability Index (MFPDI) were recorded before treatment and after 3 and 6 months. MTP Ultrasound was repeated after a minimum of 6 months on treatment.Results:53 hyperuricaemic individuals with persistent, non-episodic foot pain not meeting the ACR/EULAR 2015 gout classification criteria were recruited. At baseline MTP US DC sign, erosion and tophus occurred in 62.5%, 20.8% and 49% of cases, respectively. No US features of gout occurred in controls. No significant difference was seen in baseline serum urate between cases (481±14 mg/dL) versus controls (437±14; p=NS). Serum urate in cases fell at 3 months (325±25; p<0.01) and 6 months (248±19; p<0.01). For cases, baseline 24-hour pain VAS (46±3.9) reduced at 3 months (32±4.1; p<0.05) and 6 months (21±5.2; p<0.05) of ULT. The 7-day pain VAS (59±3.9) decreased at 3 months (35±4.5; p<0.05) and 6 months (30±5.3; P<0.05). MFPDI (17±1.4) decreased at 3 month (13±1.8; p=<0.05) and 6 months (11±2.2; p=<0.05). When cases were grouped according to the presence (N=33) or absence (N=18) of DC sign on baseline US, no differences were observed for baseline pain scores. Following ULT however, 24-hour pain VAS were significantly lower in DC positive patients at 3 months (22±4.48 DC positive vs 42±6.14 DC negative; p<0.05) and 6 months (12.±5.4 vs 33±8.4; p<0.05). The 7-day pain VAS were significantly lower in DC positive patients at 3 months (23±4.6 vs 47±6.6; p<0.05) and MFDPI were significantly lower in DC positive patients at 3 months (10±1.9 DC positive vs 19±2.9 DC negative; p<0.05).Conclusion:These findings indicate that persistent, non-episodic foot pain in hyperuricaemia is both associated with US features of MSU deposition and is responsive to ULT. Symptomatic hyperuricaemia occurring prior to episodic gout therefore represents an earlier or alternative disease presentation. Changes to the ACR/ EULAR classification criteria to include non-episodic foot pain in the presence of US features of gout may increase the sensitivity of disease classification at an early stage, leading to improved future treatment strategies and long-term outcomes.References:[1]Stewart S, Dalbeth N, Vandal AC, Rome K. Characteristics of the first metatarsophalangeal joint in gout and asymptomatic hyperuricaemia: A cross-sectional observational study. J Foot Ankle Res. 2015;8(1):1–8.Disclosure of Interests:None declared


2016 ◽  
Vol 51 (4) ◽  
pp. 301-306 ◽  
Author(s):  
Jonathan C. Hughes ◽  
Jessica L. Wallace ◽  
Candace L. Bryant ◽  
Brent E. Salvig ◽  
T. Neal Fourakre ◽  
...  

Background: With the prevalence of and hospitalizations for gout increasing, optimizing care for patients with gout is imperative. The 2012 American College of Rheumatology gout guidelines emphasize that timely monitoring is key to achieving serum urate (SUA) goals. Few studies have examined this metric following the 2012 update, and to our knowledge, none have examined a veteran population. Objective: To evaluate adherence to urate-lowering therapy (ULT) monitoring guidelines in a veteran population. Methods: This is a single-center, multisite, retrospective chart review of US veterans receiving ULT for gout within the VA (Veterans Affairs) Tennessee Valley Healthcare System from January 1, 2013, to June 30, 2015. The primary end point was percentage of patients with a SUA within 6 months of initial xanthine oxidase inhibitor prescription. Secondary end points included percentage of patients with SUA <6 mg/dL and percentage of patients with uptitration following SUA above goal. Results: A total of 601 patients met inclusion criteria for the study; after application of exclusion criteria, 505 were analyzed. Of these, 295 patients (58%) did not have a SUA drawn within 6 months, and 162 patients (32%) reached the end of the study period without SUA measured. Of 226 patients with SUA above goal on initial check, 64 (28%) had timely dose adjustment, whereas 143 patients (63%) had no adjustment. A total of 161 patients (32%) had a SUA at goal within the study period. Conclusions: Rates of ULT monitoring at a major VA medical center were suboptimal, and improved adherence to guideline recommendations is needed.


2011 ◽  
Vol 38 (7) ◽  
pp. 1385-1389 ◽  
Author(s):  
DAVID S. GOLDFARB ◽  
PATRICIA A. MacDONALD ◽  
BARBARA HUNT ◽  
LHANOO GUNAWARDHANA

Objective.Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate (sUA) levels in gouty patients who were either overproducers or underexcretors.Methods.Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2, 28-day, multicenter, randomized, double-blind, placebo-controlled trial and randomized to receive febuxostat 40 mg, 80 mg, or 120 mg daily, or placebo. The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28. Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid (uUA) from baseline to Day 28.Results.Of the 153 subjects, 118 (77%) were underexcretors (uUA ≤ 800 mg/24 h) and 32 (21%) were overproducers (uUA > 800 mg/24 h); baseline uUA data were missing for 3 subjects. Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28. Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group, for both underexcretors and overproducers.Conclusion.Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status.


Author(s):  
Pascal Richette

The general goals of gout therapy are to manage acute flares and to prevent recurrences and prevent or reverse the complications of urate deposition by lowering urate levels. The choice of drug should be made on the basis of the patient’s co-morbidities, other medications, and side effect profile. Treatment of flares can be achieved with non-steroidal anti-inflammatory drugs, colchicine, or corticosteroids (systemic or intra-articular). Interleukin-1 blockers could become an alternative in patients contraindicated for traditional anti-inflammatory agents. Lowering of urate levels below monosodium urate (MSU) saturation point with both a non-pharmacological and pharmacological approach allows to dissolve MSU crystals and to cure gout. Serum urate (SUA) levels should be maintained below 6 mg/dL (360 μ‎mol/L) or below 5 mg/dL (300 μ‎mol/L) in patients with severe gout to facilitate faster dissolution of crystals. Urate-lowering therapy (ULT) should be initiated close to the first diagnosis of gout. Allopurinol and febuxostat are the most widely used xanthine oxidase inhibitors to lower SUA levels. If the SUA target cannot be reached by these agents, uricosurics are indicated, either alone or in combination with a xanthine oxidase inhibitor. In patients with severe tophaceous gout in whom the SUA target cannot be reached with any other available drug, pegloticase is indicated. Since ULT initiation may trigger acute attacks of gout, prophylaxis with an anti-inflammatory agent is recommended, mostly with low-dose colchicine. Of note, patient education, appropriate lifestyle advice, and treatment of comorbidities are also important parts of the management of patients with gout.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Andrew Shaffer ◽  
Elizabeth Rahn ◽  
Kenneth Saag ◽  
Amy Mudano ◽  
Angelo Gaffo

Abstract Background Previous studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA. Methods Data was analyzed from a cross-over clinical trial of urate-lowering therapy in young adults without a gout diagnosis. In the control phase, sUA levels used for this analysis were collected at 2–4 week intervals. Mean coefficient of variation for sUA was determined, as were rates of conversion between normouricemia (sUA ≤6.8 mg/dL) and hyperuricemia (sUA > 6.8 mg/dL). Results Mean study participant (n = 85) age was 27.8 ± 7.0 years, with 39% female participants and 41% African-American participants. Mean sUA coefficient of variation was 8.5% ± 4.9% (1 to 23%). There was no significant difference in variation between men and women, or between participants initially normouricemic and those who were initially hyperuricemic. Among those initially normouricemic (n = 72), 21% converted to hyperuricemia during at least one subsequent measurement. The subgroup with initial sUA < 6.0 (n = 54) was much less likely to have future values in the range of hyperuricemia compared to the group with screening sUA values between 6.0–6.8 (n = 18) (7% vs 39%, p = 0.0037). Of the participants initially hyperuricemic (n = 13), 46% were later normouricemic during at least one measurement. Conclusion Single sUA measurements were unreliable in hyperuricemia classification due to spontaneous variation. Knowing this, if a single measurement must be used in classification, it is worth noting that those with an sUA of < 6.0 mg/dL were less likely to demonstrate future hyperuricemic measurements and this could be considered a safer threshold to rule out intermittent hyperuricemia based on a single measurement point. Trial registration Data from parent study ClinicalTrials.gov Identifier: NCT02038179.


2020 ◽  
Vol 27 (12) ◽  
pp. 2703-2707
Author(s):  
Muddasir Zia ◽  
Rukhshan Khurshid ◽  
Uzma Jabbar ◽  
Adnan Riaz ◽  
Roohi Jabbar ◽  
...  

Objectives: Study was designed to find out the Correlation of serum uric acid with renal function parameters in Preeclampsia. Study Design: Cross Sectional study. Setting: Sir Ganga Ram Hospital Lahore. Period: July 2016 to July 2017. Material & Methods: Level of serum uric acid, serum creatinine and blood urea of 40 Preeclamptic women and 30 gestation-matched normotensive controls were estimated. Their Demographic and clinical characteristics were noted. The blood sample was analyzed for biochemical parameters, blood urea, serum uric acid, serum creatinine and urinary protein. Result: Mean age and gestational age of women was 25 weeks with BMI 29 Kg/m2. Level of serum uric acid and blood urea and serum creatinine were increased, but significant difference only observed with serum uric acid and blood urea with marked proteinuria. An inverse relationship of serum uric acid with urinary protein was observed. A direct relationship, of serum uric acid with serum creatinine was observed. Conclusion: it is concluded that estimation of parameters of renal function of preeclamptic women are important along with hyperuicaemia.


2019 ◽  
Vol 26 (2) ◽  
pp. 338-344
Author(s):  
Stephen Eng ◽  
Chung-Shien Lee ◽  
Seungjun Ahn ◽  
Amy Sharma

Purpose Due to an increased use of rasburicase, the study’s purpose was to evaluate both the management of tumor lysis syndrome and the utilization of rasburicase in the hospital system. Additionally, the efficacy of flat dose rasburicase in lowering uric acid levels was evaluated. Based on the study’s findings, the investigators will evaluate the usefulness of implementing a tumor lysis syndrome order set. Methods This study evaluated patients from January 2013 through December 2016 for the rasburicase dose and the tumor lysis syndrome therapy administered. Results Overall, 251 patients were included: prophylactic rasburicase group (n = 125) vs. treatment rasburicase group (n = 126) and of rasburicase 3 mg (R3) group (n = 168) vs. 6 mg (R6) group (n = 83). The prophylactic rasburicase vs. treatment rasburicase group had a significantly lower rate of receiving a xanthine oxidase inhibitor (48.0% vs. 64.3%, p = 0.009), a phosphate binder (6.4% vs. 17.5%, p = 0.007) and an additional dose of rasburicase (20.8% vs. 41.3%, p = 0.001). Intravenous hydration was neither significantly different between the rasburicase groups (p = 0.399) nor between the two rasburicase dosing groups (p = 0.874). Between the rasburicase dosing groups, there was no significant difference in the rate of receiving a xanthine oxidase inhibitor (p = 0.521) or a phosphate binder (p = 0.390). R6 patients had a significantly greater reduction in uric acid change compared to R3 patients (median = −7.9 (−10.1, −5.5) vs. −4.3 (−6.0, −2.7), p < 0.0001). There was no significant difference in uric acid change between the prophylactic rasburicase and treatment rasburicase groups (p = 0.875). Conclusion The study’s findings justified the need to implement a tumor lysis syndrome order set. In the study population, utilizing a flat dosing method was effective for hyperuricemia.


Author(s):  
Rajeshwari Shastry ◽  
Prabha Adhikari M. R. ◽  
Shashidhar Kotian M.

<p><strong>Objective: </strong>To compare and evaluate the renal profile of elderly and younger diabetics.</p><p><strong>Methods: </strong>This cross sectional study was conducted in a tertiary care teaching hospital. Patients with type-2-diabetes were grouped into elderly (age≥60years) and younger diabetics. Patients’ demographics, duration of diabetes and serum creatinine were recorded. Cockcroft-Gault formula was used to calculate creatinine clearance (Clcr). Statistical analysis was done using Students’‘t’ test and Pearson’s correlation. Regression analysis to adjust for covariables was done wherever required.</p><p><strong>Results: </strong>A total of 477 diabetics were included (elderly <em>n</em>=320, young <em>n</em>=157). Body mass index (BMI) was significantly lower (p=0.003) and duration of diabetes was significantly longer (p=0.001) among elderly. Significant difference was noted in serum creatinine (1.06±0.32 vs 0.95±0.29 mg/dl; p=0.0002) and Clcr (57.82±17.41 vs 88.07±24.60 ml/min; p=0.001) between elderly and younger diabetics. Only 4.7% of elderly, whereas 47.8% of young had normal Clcr. Clcr showed a negative correlation with age in elderly (r=-0.389, p&lt;0.001) and young (r=-0.396, p&lt;0.001) and positive correlation with BMI in elderly (r=0.401, p&lt;0.001) and young(r=0.337, p&lt;0.001). Regression analysis of Clcr in elderly and young showed a positive correlation for BMI and inverse relationship for age and duration of diabetes mellitus.</p><p><strong>Conclusion: </strong>Almost 95% of the elderly and 50% of younger diabetics had impaired creatinine clearance. Renal impairment was concealed in most of them since mean serum creatinine was 1 mg/dl. Indian elderly diabetics should be considered renally impaired and drugs for all conditions need adjustment for creatinine clearance.</p>


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