Jie-Ying Wu1, Ya-Ting Chang2, Ying-Chin Lin1,3, Chia-Hwa Lee4,5,6, El-Wui Loh7, Mei-Yi Wu7,8,9, Yu-Sheng Chang9,10, Ka-Wai Tam7,11,12,13. 1. Department of Family Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. 2. School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 3. Department of Family Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 4. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. 5. Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan. 6. Department of Laboratory Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. 7. Center for Evidence-Based Health Care, Department of Medical Research, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. 8. Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. 9. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 10. Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. 11. Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan. 12. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 13. Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan.
Abstract
OBJECTIVE: To evaluate the efficacy and safety of lesinurad for the treatment of hyperuricemia in patients with gout. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). PATIENTS OR PARTICIPANTS: Five RCTs, which included 1959 patients, compared the efficacy and safety of lesinurad in patients with hyperuricemia associated with gout. MEASUREMENTS AND RESULTS: Relevant studies were identified from PubMed, EMBASE, Cochrane Library databases, and the ClinicalTrials.gov registry. Two reviewers independently assessed the studies. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random-effect model. The primary outcomes were the proportion of patients achieving target serum uric acid (sUA) levels by month 6 and the mean sUA levels at month 6 and month 12. Gout-related outcomes were also assessed. The secondary outcome was the number of treatment-emergent adverse events (TEAEs). Compared with xanthine oxidase inhibitor (XOI) monotherapy, lesinurad 200 mg or 400 mg in combination with allopurinol or febuxostat exhibited a higher proportion of patients achieving target sUA levels of < 6.0 mg/dl or < 5.0 mg/dl, respectively, by month 6. Lesinurad-plus-XOI groups also significantly sustained lower mean sUA levels at month 6 and month 12 compared to XOI alone group. In gout-related outcomes, no significant treatment group differences favored lesinurad. The number of TEAEs was comparable between the lesinurad 200 mg-plus-XOI group and the XOI-monotherapy group. Although lesinurad 400 mg monotherapy demonstrated superior efficacy compared with placebo, significantly more TEAEs occurred. CONCLUSIONS: Although the combination of lesinurad 200 mg and XOI is effective and well tolerated for treating patients with gout who have not achieved an adequate response to XOI monotherapy, clinical gout-related outcomes were not improved. Therefore, additional studies investigating the long-term clinical implication of lesinurad are warranted.
OBJECTIVE: To evaluate the efficacy and safety of lesinurad for the treatment of hyperuricemia in patients with gout. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). PATIENTS OR PARTICIPANTS: Five RCTs, which included 1959 patients, compared the efficacy and safety of lesinurad in patients with hyperuricemia associated with gout. MEASUREMENTS AND RESULTS: Relevant studies were identified from PubMed, EMBASE, Cochrane Library databases, and the ClinicalTrials.gov registry. Two reviewers independently assessed the studies. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random-effect model. The primary outcomes were the proportion of patients achieving target serum uric acid (sUA) levels by month 6 and the mean sUA levels at month 6 and month 12. Gout-related outcomes were also assessed. The secondary outcome was the number of treatment-emergent adverse events (TEAEs). Compared with xanthine oxidase inhibitor (XOI) monotherapy, lesinurad 200 mg or 400 mg in combination with allopurinol or febuxostat exhibited a higher proportion of patients achieving target sUA levels of < 6.0 mg/dl or < 5.0 mg/dl, respectively, by month 6. Lesinurad-plus-XOI groups also significantly sustained lower mean sUA levels at month 6 and month 12 compared to XOI alone group. In gout-related outcomes, no significant treatment group differences favored lesinurad. The number of TEAEs was comparable between the lesinurad 200 mg-plus-XOI group and the XOI-monotherapy group. Although lesinurad 400 mg monotherapy demonstrated superior efficacy compared with placebo, significantly more TEAEs occurred. CONCLUSIONS: Although the combination of lesinurad 200 mg and XOI is effective and well tolerated for treating patients with gout who have not achieved an adequate response to XOI monotherapy, clinical gout-related outcomes were not improved. Therefore, additional studies investigating the long-term clinical implication of lesinurad are warranted.