Meida Fan1,2, Jian Liu3, Bingcheng Zhao3, Xinyu Wu2, Xuefeng Li4,5,6, Jieruo Gu7, Naomi Schlesinger8. 1. Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China. 2. Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Tianhe, Guangzhou, 510630, People's Republic of China. 3. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China. 4. The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital; State Key Laboratory of Respiratory Disease, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Xinzao, Panyu, Guangzhou, 511436, Guangdong, People's Republic of China. xuefengli@gzhmu.edu.cn. 5. Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, 518001, Guangdong, People's Republic of China. xuefengli@gzhmu.edu.cn. 6. Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, Guangdong, People's Republic of China. xuefengli@gzhmu.edu.cn. 7. Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Tianhe, Guangzhou, 510630, People's Republic of China. gujieruo@163.com. 8. Department of Medicine, Division of Rheumatology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, 08901, USA. schlesna@aol.com.
Abstract
OBJECTIVES: To assess the efficacy and safety of the commonly used urate-lowering therapies (ULTs): febuxostat, allopurinol, and lesinurad in hyperuricemic patients with gout. METHODS: We included all randomized controlled trials (RCTs) that compared ULTs with placebo or head to head. The primary efficacy endpoint was the proportion of subjects achieving the target serum urate (SU) level at month 6. Safety outcomes included total adverse events (AEs), serious AEs, withdrawals due to AEs, and AEs per organ system. A Bayesian network model was used to compare all ULTs with placebo and among themselves. RESULTS: Fifteen RCTs were included for the analysis, in which 7968 patients were randomly assigned to take either placebo or one of 11 ULTs: allopurinol, febuxostat 40/80/120/240 mg/day, lesinurad 400 mg/day, lesinurad 200/400/600 mg/day plus allopurinol, and lesinurad 200/400 mg/day plus febuxostat. All ULTs were effective in achieving the target SU level at month 6 compared with placebo (ORs between 26.81 and 1928). Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. Furthermore, the lesinurad combination with xanthine oxidase inhibitor (XOI) groups had a higher proportion of patients achieving the target SU level than the febuxostat 40 mg/day group (ORs between 2.89 and 9.17), the allopurinol group (ORs between 3.56 and 11.27), or the lesinurad 400 mg/day monotherapy group (ORs between 12.30 and 39.17) but might have a high risk of AEs. CONCLUSIONS: All ULTs are effective in achieving the target SU level compared with placebo in hyperuricemic patients with gout. Lesinurad in combination with febuxostat or allopurinol is effective in urate lowering, especially for patients with inadequate response to XOI monotherapy. Key Points • All urate-lowering therapies (ULTs) were effective in achieving the target serum urate (SU) level at month 6 compared with placebo in hyperuricemic patients with gout. • Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. • Lesinurad in combination with febuxostat or allopurinol was effective in urate lowering, especially for patients with inadequate response to xanthine oxidase inhibitor monotherapy, but might have a high risk of AEs.
OBJECTIVES: To assess the efficacy and safety of the commonly used urate-lowering therapies (ULTs): febuxostat, allopurinol, and lesinurad in hyperuricemic patients with gout. METHODS: We included all randomized controlled trials (RCTs) that compared ULTs with placebo or head to head. The primary efficacy endpoint was the proportion of subjects achieving the target serum urate (SU) level at month 6. Safety outcomes included total adverse events (AEs), serious AEs, withdrawals due to AEs, and AEs per organ system. A Bayesian network model was used to compare all ULTs with placebo and among themselves. RESULTS: Fifteen RCTs were included for the analysis, in which 7968 patients were randomly assigned to take either placebo or one of 11 ULTs: allopurinol, febuxostat 40/80/120/240 mg/day, lesinurad 400 mg/day, lesinurad 200/400/600 mg/day plus allopurinol, and lesinurad 200/400 mg/day plus febuxostat. All ULTs were effective in achieving the target SU level at month 6 compared with placebo (ORs between 26.81 and 1928). Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. Furthermore, the lesinurad combination with xanthine oxidase inhibitor (XOI) groups had a higher proportion of patients achieving the target SU level than the febuxostat 40 mg/day group (ORs between 2.89 and 9.17), the allopurinol group (ORs between 3.56 and 11.27), or the lesinurad 400 mg/day monotherapy group (ORs between 12.30 and 39.17) but might have a high risk of AEs. CONCLUSIONS: All ULTs are effective in achieving the target SU level compared with placebo in hyperuricemic patients with gout. Lesinurad in combination with febuxostat or allopurinol is effective in urate lowering, especially for patients with inadequate response to XOI monotherapy. Key Points • All urate-lowering therapies (ULTs) were effective in achieving the target serum urate (SU) level at month 6 compared with placebo in hyperuricemic patients with gout. • Febuxostat 80/120/240 mg/day was superior to allopurinol and well tolerated for urate reduction. And as febuxostat dosage increased, more patients achieved the target SU level. • Lesinurad in combination with febuxostat or allopurinol was effective in urate lowering, especially for patients with inadequate response to xanthine oxidase inhibitor monotherapy, but might have a high risk of AEs.
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