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. 2023 Dec 11;25(1):241.
doi: 10.1186/s13075-023-03228-y.

Response to febuxostat according to clinical subtypes of hyperuricemia: a prospective cohort study in primary gout

Han Qi #  1   2   3   4 , Mingshu Sun #  4   5 , Robert Terkeltaub #  6 , Xiaomei Xue #  1   2 , Xinde Li #  2 , Lingling Cui #  2 , Yuwei He  2 , Fei Yan  1   2 , Ruixia Sun  1 , Ying Chen  1 , Zhaotong Jia  1 , Xiaoyu Cheng  1 , Lidan Ma  1 , Tian Liu  1 , Nicola Dalbeth  7 , Changgui Li  8   9   10   11
Affiliations

Response to febuxostat according to clinical subtypes of hyperuricemia: a prospective cohort study in primary gout

Han Qi et al. Arthritis Res Ther. .

Abstract

Background: While xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia.

Methods: A prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12.

Results: Fewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41-0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62-0.89, P = 0.001) were independently associated with lower rates of achieving SU target.

Conclusions: People with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.

Keywords: Clinical subtypes of hyperuricemia; Febuxostat; Gout.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Participant flow throughout study
Fig. 2
Fig. 2
Serum urate lowering efficacy of febuxostat according to subtype of hyperuricemia. A Proportion of participants with SU < 6.0 mg/dL at weeks 4, 8, and 12 using per-protocol analysis. B Proportion of SU < 5.0 mg/dL at weeks 4, 8, and 12 using per-protocol analysis. C Proportion of participants with SU < 6.0 mg/dL at weeks 4, 8, and 12 using intention-to-treat analysis. D Proportion of SU < 5.0 mg/dL at weeks 4, 8, and 12 using intention-to-treat analysis. E Proportion of participants requiring febuxostat dose escalation to 40 mg daily. PP per-protocol, ITT intention-to-treat. Asterisk indicates compared with the renal overload subtype, P < 0.05, number sign indicates compared with the renal underexcretion subtype, P < 0.05
Fig. 3
Fig. 3
Odds ratio (OR) (95% CI) of baseline predictors associated with achieving SU target (SU < 6.0 mg/dL) in multivariable analysis. A All participants. B Participants with renal overload subtype. C Participants with renal underexcretion subtype. D Participants with combined subtype
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