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Low Febuxostat Dose Appropriate For Patients With Gout And Impaired Renal Function – Renal And Urology News – Renal.PlatoHealth.ai

Patients with gout who had stage 4 to 5 chronic kidney disease (CKD) initiated febuxostat at lower doses than those with stage 3 disease, and required significantly lower daily and cumulative febuxostat doses in order to achieve serum urate (SU) targets, according to study results published in Joint Bone Spine.

Febuxostat is a widely used urate-lowering therapy (ULT). It is particularly beneficial for patients with gout and chronic kidney disease (CKD), as its clearance is not primarily affected by kidney function. While previous studies have explored factors influencing the achievement of target SU levels in patients with gout, particularly focusing on allopurinol, there is limited information regarding the appropriate febuxostat dosage required to reach target levels. Thus, researchers aimed to determine the febuxostat dose required to achieve target SU levels among patients with gout with different levels of renal function. 

A retrospective cohort study was conducted at Asan Medical Center in Seoul, South Korea. Adult patients diagnosed with gout who were prescribed febuxostat and had initial SU levels of at least 6 mg/dL were included in the analysis. Patients were categorized into 3 groups based on CKD stage at febuxostat initiation: normal (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2), CKD 3 (eGFR <60 and ≥30 mL/min/1.73 m2), and CKD 4 to 5 (eGFR <30 mL/min/1.73 m2).

The primary study endpoint was the proportion of patients who achieved a target SU level of less than 6 mg/dL after treatment with febuxostat.

For patients with impaired renal function, a low dose of febuxostat may be considered for the management of gouty arthritis.

A total of 778 patients treated with febuxostat who had at least 4 months of follow-up were included in the analysis. The majority of patients were men (91.4%) with a median age of 52.0 years.

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Overall, 427 patients (54.9%) had normal eGFR levels, 212 (27.2%) had stage 3 CKD, and 139 (17.9%) had stage 4 to 5 CKD.

Stratified by baseline eGFR levels, significant differences were observed among these groups in terms of age, sex, and body mass index, with a higher prevalence of comorbidities in the CKD 4 to 5 group. Comorbidities included hypertension, diabetes, and cardiovascular disease. Baseline SU levels were higher in the CKD 4 to 5 group (9.6 mg/dL) compared with the CKD 3 (8.7 mg/dL) and normal (8.4 mg/dL) groups.

An initial febuxostat dose of 80 mg was less common among the CKD 3 (37.7%) and CKD 4 to 5 (18.0%) groups compared with the normal group (40.5%); 40 mg was the most commonly prescribed dose across all groups, with doses less than 40 mg more frequently prescribed in the CKD 4 to 5 group (28.1%) vs the CKD 3 (8.0%) and normal (3.5%) groups.

In total, 87.0% of patients achieved target SU levels following treatment with ULT. However, the proportion of patients achieving target SU levels was lower in the CKD 4 to 5 group (82.0%) compared with the normal (89.2%) and CKD 3 (85.8%) groups (P <.01).

Notably, the CKD 4 to 5 group required a significantly lower cumulative febuxostat dose (5.9 g) in order to reach the target SU level, compared with the normal and CKD 3 groups (both P <.01).

Additionally, febuxostat dose at the time of SU target achievement was significantly lower in the CKD 4 to 5 group (50.0±16.5 mg) compared with the normal (60.0±19.8 mg; P <.01) and CKD 3 (60.0±19.5 mg; P <.01) groups.

Linear regression analysis revealed that female sex was inversely associated with cumulative febuxostat dose (Beta, -2.046; 95% CI, -14.046 to -0.287; P <.05) and baseline SU levels were significantly positively associated (Beta, 5.584; 95% CI, 1.917-3.941; P <.001).

Notably, CKD stage 4 to 5 had a significant inverse association with the cumulative febuxostat dose required to achieve target SU levels (Beta, -2.334; 95% CI, -6.672 to -0.574; P <.05).

According to multivariable analysis, patients with CKD 4 to 5 (odds ratio [OR] OR, 0.571; 95% CI, 0.332-0.980; P <.05) and baseline SU levels over 8 mg/dL (OR, 0.210; 95% CI, 0.075-0.583; P <.01) were at a greater risk of failing to achieve target SU levels.

Study limitations included reduced generalizability due to the solely Asian patient population and the retrospective study design. 

The study authors concluded, “[F]or patients with impaired renal function, a low dose of febuxostat may be considered for the management of gouty arthritis.

This article originally appeared on Rheumatology Advisor