Urate-lowering Efficacy Of Febuxostat Research Articles

The safety and urate-lowering efficacy of febuxostat in patients undergoing peritoneal dialysis: a retrospective single-arm cohort study of 84 patients.

Studies have shown that hyperuricemia (HUA) is an independent risk factor for all-cause death and residual kidney function loss in peritoneal dialysis (PD) patients. The control of blood uric acid (UA) is an important link to improve the prognosis of end-stage renal disease (ESRD). As a therapeutic drug for HUA, febuxostat is rarely studied in PD patients. The purpose of our study is to investigate the safety, efficacy, and effect on residual renal function (RRF) of febuxostat in patients undergoing PD. This is a retrospective single-arm cohort study. During the study period which from September 2016 to November 2020, 191 patients underwent PD at this hospital. Among these patients, 84 were administrated for over a period of 3 months and were eventually included. These 84 patients (51 males and 33 females; average age: 55.18 years) were undergoing PD complicated with HUA or gout who received febuxostat during a regular follow-up from January 2018 to November 2020. Serum UA (sUA) levels, blood routine, liver function, and RRF were compared before and after febuxostat administration. Adverse events (AEs) resulting from febuxostat treatment were collected from medical records. All 84 patients were administered febuxostat for over 3 months, including 39 for over 6 months and 26 for over 12 months. Some 60 patients were treated with febuxostat dose of 20 mg/day and the remaining 24 patients received 40 mg/day. Compared with pretreatment level, the mean sUA level was observed to be markedly reduced at 1 month after febuxostat administration (320.2±87.27 vs. 498.8±81.47 µmol/L, P<0.0001) and at 3 months (291.6±82.66 vs. 498.8±81.47 µmol/L, P<0.0001) and subsequently remained at a significantly low level for 12 months. Only 5 patients stopped febuxostat because of its associated AEs. An initial dose of 40 mg/day was associated with a higher rate of AEs compared with dose of 20 mg/day (25% vs. 18.33%, respectively). After febuxostat treatment, no significant differences were observed between RRF in the two groups. Febuxostat may be safe and efficient in patients undergoing PD and may not impair RRF. Febuxostat administration at dose of 20 mg/day may be an appropriate dose for patients undergoing PD.

Renal safety and urate-lowering efficacy of febuxostat in gout patients with stage 4-5 chronic kidney disease not yet on dialysis.

Background/AimsThe safety and efficacy of febuxostat in patients with stage 4–5 chronic kidney disease (CKD) are still unclear owing to a lack of studies in these patients. Therefore, we aimed to evaluate the effect of febuxostat on renal function, general safety, and efficacy in gout patients with stage 4–5 CKD.MethodsAmong 739 patients who had been administered febuxostat from May 2012 to December 2016 at a single hospital in Korea, 370 patients who had been monitored for 1 year were analyzed. Serum uric acid levels and estimated glomerular filtration rate (eGFR) of patients with gouty arthritis were collected at baseline and 1 year after febuxostat administration.ResultsAmong the 370 patients, 280 patients were stage 1–3 CKD, 63 patients were stage 4–5 CKD, and 27 patients were on dialysis. The eGFR of 63 patients with stage 4–5 CKD, excluding dialysis patients, was 19.84 ± 7.08 mL/min/1.73 m2 when they began to take febuxostat and 23.49 ± 16.67 mL/min/1.73 m2 after 12 months (p = 0.13). The urate-lowering effect after 12 months of febuxostat medication showed statistical significance (8.96 ± 2.31 mg/dL at baseline and 4.88 ± 1.68 mg/dL after 12 months, p < 0.01). The difference in incidence of adverse events among patients with stage 1–3 CKD, those with stage 4–5 CKD, and those on dialysis was not significant.ConclusionsFebuxostat demonstrated renal safety and good urate-lowering efficacy in gout patients with stage 4–5 CKD, who are not yet on dialysis.

Febuxostat: a new drug for an old disease. Do we really need it?

BACKGROUND Febuxostat is a non-purine selective inhibitor of xanthine oxidase whose therapeutic effect is decreasing the serum uric acid concentration. Febuxostat has a marketing authorisation for the treatment of chronic hyperuricaemia in conditions where urate/uric acid deposition has already occurred. The recommended dose of febuxostat is 80 mg once daily. If the person’s serum uric acid concentration is above 6 mg/dL after 2-4 weeks, febuxostat 120 mg once daily may be considered. The most common side effects associated with febuxostat are diarrhoea, nausea, headache, liver function test abnormalities and rash. The evidence in support of the clinical effectiveness of febuxostat in comparison with allopurinol is not strong. DISCUSSION A meta-analysis showed that although the urate-lowering efficacy of febuxostat was statistically significantly higher than fixed-dose allopurinol (300 mg/day), a higher proportion of patients receiving febuxostat needed treatment for gout flares compared with those receiving fixed-dose allopurinol. For the febuxostat 80 mg/day group this difference was not statistically significant (p &gt; 0.18), but for the 120 mg/day febuxostat group it was. Moreover, guidelines recommend dose titration for allopurinol according to therapeutic targets. It is possible that dose-titrated allopurinol may be more effective than fixed-dose allopurinol. CONCLUSIONS Febuxostat is a plausible improvement on current second-line options. These options are considered where allopurinol is not appropriate, e.g. because of chronic kidney disease, intolerance or lack of response.

Safety and Efficacy of Febuxostat Treatment in Subjects with Gout and Severe Allopurinol Adverse Reactions

Allopurinol, a purine base analog inhibitor of xanthine oxidase (XO) activity, remains the standard for pharmacologic urate-lowering management of gout. Allopurinol is efficacious and safe in most patients, but intolerance is estimated to occur in up to 10% of treated patients. Severe or life-threatening allopurinol adverse reactions (AE) occur much less frequently, and include severe cutaneous allopurinol reactions, vasculitis, and/or a multisystem allopurinol hypersensitivity syndrome. During clinical development of febuxostat (FEB), a recently approved non-purine analog inhibitor of XO, subjects with severe allopurinol intolerance were excluded from randomized double-blind FEB/allopurinol comparative trials. In this retrospective study, safety and urate-lowering efficacy of FEB was assessed in 13 successively encountered gout patients with prior documented severe allopurinol reactions. FEB was well tolerated in 12 of 13 patients, each of whom remains on treatment. One patient previously hospitalized with documented exfoliative erythroderma during allopurinol treatment, developed biopsy-confirmed cutaneous leukocytoclastic vasculitis. None of the other 12 patients treated with FEB showed rash, worsening hepatic function, blood cytopenia or eosinophilia. In 12 of our 13 gout patients with previously documented severe allopurinol AE, FEB treatment was safe. However, the development of a hypersensitivity type cutaneous vasculitis (likely but not definitively FEB-related) early in treatment mandates caution, careful dose escalation, and close monitoring when FEB urate-lowering therapy of allopurinol-intolerant patients is considered.

Febuxostat (TMX‐67), a Novel, Non‐Purine, Selective Inhibitor of Xanthine Oxidase, Is Safe and Decreases Serum Urate in Healthy Volunteers

AbstractFor Abstract see ChemInform Abstract in Full Text.