Impact of Febuxostat on Renal Function in Gout Patients With Moderate‐to‐Severe Renal Impairment

Abstract

Objective Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate‐to‐severe renal impairment (estimated glomerular filtration rate [GFR] 15–50 ml/minute/1.73 m2). Methods Ninety‐six gout patients with moderate‐to‐severe renal impairment were enrolled in a 12‐month multicenter, randomized, double‐blind, placebo‐controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12. Results At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment‐emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses. Conclusion Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate‐to‐severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function.

Febuxostat in patients with hyperuricemia and severe chronic kidney disease

“…Thus, renal function should be regularly monitored during drug treatment for ensuring safety. No serious adverse reaction occurred during the study, which is similar to the finding in previous study using febuxostat in severe CKD patients (Sircar et al, 2015;Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014;Sakai et al, 2014). The results indicate the safety of febuxostat use in CKD patients.…”

“…However, previous information on the efficacy and safety of febuxostat use in CKD patients above stage 3 is limited. Several studies explored the efficacy and safety of using febuxostat for treating patients undergoing advanced CKD treatment (Table 5) (Sircar et al, 2015;Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014;Sakai et al, 2014). However, because of the limited number of patients included in this study and lower dosages used, further research is required for verifying the results.…”

“…To increase the clinical use and safety of febuxostat, several recent studies focused on its efficacy and safety in patients with severe CKD. However, the number of included patients was low (Saag et al, 2016;Hira et al, 2015;Juge et al, 2017;Shibagaki et al, 2014). The present study assessed the efficacy and safety of febuxostat in controlling hyperuricemia in patients with severe CKD.…”

“…Previous studies have shown that hyperuricemia is associated with an increased plasma creatinine level, which is a risk factor for a low estimated glomerular filtration rate (eGFR), and can affect the progress of renal disease (Sircar et al, 2015). The risk of kidney failure is eight times higher in patients with serum uric acid (sUA) levels >8.5 mg/dl than in those with sUA levels of 5.0 to 6.4 mg/dl (Saag et al, 2016). A previous epidemiological study in Japan showed that hyperuricemia is significantly associated with the incidence of end-stage renal disease (ESRD), and sUA E-mail: 1000563@ms.kmuh.org.tw.…”

Gouty Arthritis – Modern View of the Problem

“…Фебуксостат, как и аллопуринол, ингиби-рует фермент путем присоединения к молибден-птери-новому центру, единому у всех пуринов, но, в отличие от аллопуринола, ингибирующего лишь редуцированную форму фермента, фебуксостат формирует комплекс с обеими формами КО -редуцированной и оксидирован-ной, что обеспечивает более выраженное снижение уровня МК. Кроме того, имеются данные, что у пациен-тов с поражением почек фебуксостат не приводит к про-грессированию почечной недостаточности [20,29].…”