Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout

A Systematic Review and Meta-Analysis of Randomized Controlled Trials

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)1106-1119
頁數14
期刊Pharmacotherapy
38
發行號11
DOIs
出版狀態已發佈 - 十一月 1 2018

指紋

Hyperuricemia
Gout
Xanthine Oxidase
Meta-Analysis
Randomized Controlled Trials
Safety
Uric Acid
Serum
Therapeutics
lesinurad
Allopurinol
PubMed
Libraries
Registries
Placebos
Databases

ASJC Scopus subject areas

  • Pharmacology (medical)

引用此文

@article{7a33b91fd0c3469cb9cdc50a601ea80a,
title = "Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials",
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.",
keywords = "gout, hyperuricemia, lesinurad, urate-lowering therapy, uricosuric agent",
author = "Wu, {Jie Ying} and Chang, {Ya Ting} and Lin, {Ying Chin} and Lee, {Chia Hwa} and Loh, {El Wui} and Wu, {Mei Yi} and Chang, {Yu Sheng} and Tam, {Ka Wai}",
year = "2018",
month = "11",
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doi = "10.1002/phar.2183",
language = "English",
volume = "38",
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journal = "Pharmacotherapy",
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T1 - Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout

T2 - A Systematic Review and Meta-Analysis of Randomized Controlled Trials

AU - Wu, Jie Ying

AU - Chang, Ya Ting

AU - Lin, Ying Chin

AU - Lee, Chia Hwa

AU - Loh, El Wui

AU - Wu, Mei Yi

AU - Chang, Yu Sheng

AU - Tam, Ka Wai

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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.

AB - 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.

KW - gout

KW - hyperuricemia

KW - lesinurad

KW - urate-lowering therapy

KW - uricosuric agent

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