A Randomized, Double-Blind, Non-Inferiority Study of Febuxostat Versus Allopurinol in Hyperuricemic Chinese Subjects With or Without Gout

Fengchun Zhang; Zhichun Liu; Lindi Jiang; Hao Zhang; Dongbao Zhao; Yang Li; Hejian Zou; Xiaoyue Wang; Xiangpei Li; Bingyin Shi; Jianhua Xu; Hongjie Yang; Shaoxian Hu; Shen Qu

doi:10.1007/s40744-019-00173-8

A Randomized, Double-Blind, Non-Inferiority Study of Febuxostat Versus Allopurinol in Hyperuricemic Chinese Subjects With or Without Gout

Rheumatol Ther. 2019 Dec;6(4):543-557. doi: 10.1007/s40744-019-00173-8. Epub 2019 Sep 17.

Authors

Fengchun Zhang¹, Zhichun Liu², Lindi Jiang³, Hao Zhang⁴, Dongbao Zhao⁵, Yang Li⁶, Hejian Zou⁷, Xiaoyue Wang⁸, Xiangpei Li⁹, Bingyin Shi¹⁰, Jianhua Xu¹¹, Hongjie Yang¹², Shaoxian Hu¹³, Shen Qu¹⁴

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. zhangfccra@aliyun.com.
² Department of Rheumatology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
³ Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Department of Nephrology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
⁵ Department of Rheumatology and Immunology, Shanghai Changhai Hospital, Shanghai, China.
⁶ Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
⁷ Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.
⁸ Department of Endocrinology, The First People Hospital of Yueyang, Yueyang, Hunan, China.
⁹ Department of Rheumatology and Immunology, The First Affiliated Hospital, University of Science and Technology of China, Hefei, Anhui, China.
¹⁰ Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
¹¹ Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
¹² Department of Endocrinology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
¹³ Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
¹⁴ Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Zhabei, Shanghai, China.

Abstract

Introduction: This 24-week randomized, double-blind, non-inferiority study compared the efficacy and safety of febuxostat, a xanthine oxidase inhibitor, with allopurinol using an up-titration method in hyperuricemic Chinese subjects with or without gout.

Methods: Eligible adults (serum uric acid [SUA] > 7.0 mg/dl with a history of gout, SUA ≥ 8.0 mg/dl with complications or SUA ≥ 9.0 mg/dl without complications) were randomized (1:1:1) to febuxostat 40 mg/day, 80 mg/day, or allopurinol 300 mg/day. Starting doses of febuxostat 20 mg/day and allopurinol 100 mg/day were up-titrated, up to 16 weeks, to the randomized doses and maintained to week 24. Primary endpoint was non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day based on the percentage of subjects with SUA ≤ 6.0 mg/dl at week 24. The same comparison was made between febuxostat 60 mg/day or 80 mg/day versus allopurinol 300 mg/day. Safety assessments included measurement of treatment-emergent adverse events (TEAEs).

Results: The per-protocol population comprised 472 subjects. Non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not demonstrated based on the protocol-defined margin of - 10% (44.7 vs. 50.0%; - 5.3% difference; 95% confidence interval [CI]: - 16.4%, 5.8%); however, superiority over allopurinol 300 mg/day was demonstrated for febuxostat 60 mg/day at week 16 (66.3 vs. 51.2%; a 15.0% difference; 95% CI: 4.2%, 25.9%) and febuxostat 80 mg/day at week 24 (70.0 vs. 50.0%; a 20.0% difference; 95% CI: 9.3%, 30.7%). The frequency of TEAEs was similar across groups, with gout flares occurring frequently.

Conclusions: Using a novel dose-titration method, although the primary endpoint of non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not reached, non-inferiority and superiority of febuxostat 60 mg/day and 80 mg/day versus allopurinol 300 mg/day was demonstrated at weeks 16 and 24, respectively. Febuxostat demonstrated an acceptable tolerability profile in the treatment of hyperuricemia in Chinese subjects with or without gout.

Trial registration: JapicCTI-132106.

Funding: Astellas Pharma Global Development, Inc.

Keywords: Febuxostat; Gout; Hyperuricemia; Xanthine oxidase inhibitor.

Grants and funding

n/a/Astellas Pharma Global Development