Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
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 o...
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| Veröffentlicht in: | Pharmacotherapy 2018-11, Vol.38 (11), p.1106-1119 |
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| creator | Wu, Jie‐Ying Chang, Ya‐Ting Lin, Ying‐Chin Lee, Chia‐Hwa Loh, El‐Wui Wu, Mei‐Yi Chang, Yu‐Sheng Tam, Ka‐Wai |
| description | 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. |
| doi_str_mv | 10.1002/phar.2183 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2111745519</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2111745519</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3793-67875f169b55d487437fd2c1ba65320b35eb2a5bf85ce64dabfcd110e4e3d6a3</originalsourceid><addsrcrecordid>eNp1kctu1DAUhi0EokNhwQsgS2zoIq0vubKLRm0HaSqq6ewjxz5WXSXxYDsdhVUfoS_Ay_EkOJ3CAqmrY_l8_o6Of4Q-UnJKCWFnu1vhThkt-Su0oGWRJRWl6Wu0IKwoEkJIeYTeeX8XUZqn7C064oSlOauqBfp1rrWRQk5YDArfCA1hwlbjNXgzjE4obAZ8LYKBIXi8N-EWr6YduNEZCb0RuPbeSiMCqEP30o7hK67xzeQD9PGhxBu4N7B_GnAFQfx-eKwH0U3e-HnSJt7b3vyMgqUdgrNdF49bZ0Tn36M3Ohb48FyP0fbifLtcJevvl9-W9TqRvKh4khdxaU3zqs0ylZZFygutmKStyDPOSMszaJnIWl1mEvJUiVZLRSmBFLjKBT9GXw7anbM_RvCh6Y2X0HViADv6hlFKizTLaBXRz_-hd3Z0cZ2Zit9KeVqWkTo5UNJZ7x3oZudML9zUUNLMkTVzZM0cWWQ_PRvHtgf1j_ybUQTODsDedDC9bGquV_XmSfkHD3ajXw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2130213488</pqid></control><display><type>article</type><title>Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Wu, Jie‐Ying ; Chang, Ya‐Ting ; Lin, Ying‐Chin ; Lee, Chia‐Hwa ; Loh, El‐Wui ; Wu, Mei‐Yi ; Chang, Yu‐Sheng ; Tam, Ka‐Wai</creator><creatorcontrib>Wu, Jie‐Ying ; Chang, Ya‐Ting ; Lin, Ying‐Chin ; Lee, Chia‐Hwa ; Loh, El‐Wui ; Wu, Mei‐Yi ; Chang, Yu‐Sheng ; Tam, Ka‐Wai</creatorcontrib><description>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.</description><identifier>ISSN: 0277-0008</identifier><identifier>EISSN: 1875-9114</identifier><identifier>DOI: 10.1002/phar.2183</identifier><identifier>PMID: 30246299</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Allopurinol ; Clinical trials ; Gout ; Hyperuricemia ; lesinurad ; Meta-analysis ; Patients ; Randomization ; Rheumatism ; Safety ; Systematic review ; urate‐lowering therapy ; Uric acid ; uricosuric agent ; Xanthine oxidase</subject><ispartof>Pharmacotherapy, 2018-11, Vol.38 (11), p.1106-1119</ispartof><rights>2018 Pharmacotherapy Publications, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3793-67875f169b55d487437fd2c1ba65320b35eb2a5bf85ce64dabfcd110e4e3d6a3</citedby><cites>FETCH-LOGICAL-c3793-67875f169b55d487437fd2c1ba65320b35eb2a5bf85ce64dabfcd110e4e3d6a3</cites><orcidid>0000-0002-1994-834X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fphar.2183$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fphar.2183$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30246299$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Jie‐Ying</creatorcontrib><creatorcontrib>Chang, Ya‐Ting</creatorcontrib><creatorcontrib>Lin, Ying‐Chin</creatorcontrib><creatorcontrib>Lee, Chia‐Hwa</creatorcontrib><creatorcontrib>Loh, El‐Wui</creatorcontrib><creatorcontrib>Wu, Mei‐Yi</creatorcontrib><creatorcontrib>Chang, Yu‐Sheng</creatorcontrib><creatorcontrib>Tam, Ka‐Wai</creatorcontrib><title>Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials</title><title>Pharmacotherapy</title><addtitle>Pharmacotherapy</addtitle><description>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.</description><subject>Allopurinol</subject><subject>Clinical trials</subject><subject>Gout</subject><subject>Hyperuricemia</subject><subject>lesinurad</subject><subject>Meta-analysis</subject><subject>Patients</subject><subject>Randomization</subject><subject>Rheumatism</subject><subject>Safety</subject><subject>Systematic review</subject><subject>urate‐lowering therapy</subject><subject>Uric acid</subject><subject>uricosuric agent</subject><subject>Xanthine oxidase</subject><issn>0277-0008</issn><issn>1875-9114</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kctu1DAUhi0EokNhwQsgS2zoIq0vubKLRm0HaSqq6ewjxz5WXSXxYDsdhVUfoS_Ay_EkOJ3CAqmrY_l8_o6Of4Q-UnJKCWFnu1vhThkt-Su0oGWRJRWl6Wu0IKwoEkJIeYTeeX8XUZqn7C064oSlOauqBfp1rrWRQk5YDArfCA1hwlbjNXgzjE4obAZ8LYKBIXi8N-EWr6YduNEZCb0RuPbeSiMCqEP30o7hK67xzeQD9PGhxBu4N7B_GnAFQfx-eKwH0U3e-HnSJt7b3vyMgqUdgrNdF49bZ0Tn36M3Ohb48FyP0fbifLtcJevvl9-W9TqRvKh4khdxaU3zqs0ylZZFygutmKStyDPOSMszaJnIWl1mEvJUiVZLRSmBFLjKBT9GXw7anbM_RvCh6Y2X0HViADv6hlFKizTLaBXRz_-hd3Z0cZ2Zit9KeVqWkTo5UNJZ7x3oZudML9zUUNLMkTVzZM0cWWQ_PRvHtgf1j_ybUQTODsDedDC9bGquV_XmSfkHD3ajXw</recordid><startdate>201811</startdate><enddate>201811</enddate><creator>Wu, Jie‐Ying</creator><creator>Chang, Ya‐Ting</creator><creator>Lin, Ying‐Chin</creator><creator>Lee, Chia‐Hwa</creator><creator>Loh, El‐Wui</creator><creator>Wu, Mei‐Yi</creator><creator>Chang, Yu‐Sheng</creator><creator>Tam, Ka‐Wai</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1994-834X</orcidid></search><sort><creationdate>201811</creationdate><title>Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials</title><author>Wu, Jie‐Ying ; Chang, Ya‐Ting ; Lin, Ying‐Chin ; Lee, Chia‐Hwa ; Loh, El‐Wui ; Wu, Mei‐Yi ; Chang, Yu‐Sheng ; Tam, Ka‐Wai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3793-67875f169b55d487437fd2c1ba65320b35eb2a5bf85ce64dabfcd110e4e3d6a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Allopurinol</topic><topic>Clinical trials</topic><topic>Gout</topic><topic>Hyperuricemia</topic><topic>lesinurad</topic><topic>Meta-analysis</topic><topic>Patients</topic><topic>Randomization</topic><topic>Rheumatism</topic><topic>Safety</topic><topic>Systematic review</topic><topic>urate‐lowering therapy</topic><topic>Uric acid</topic><topic>uricosuric agent</topic><topic>Xanthine oxidase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Jie‐Ying</creatorcontrib><creatorcontrib>Chang, Ya‐Ting</creatorcontrib><creatorcontrib>Lin, Ying‐Chin</creatorcontrib><creatorcontrib>Lee, Chia‐Hwa</creatorcontrib><creatorcontrib>Loh, El‐Wui</creatorcontrib><creatorcontrib>Wu, Mei‐Yi</creatorcontrib><creatorcontrib>Chang, Yu‐Sheng</creatorcontrib><creatorcontrib>Tam, Ka‐Wai</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Jie‐Ying</au><au>Chang, Ya‐Ting</au><au>Lin, Ying‐Chin</au><au>Lee, Chia‐Hwa</au><au>Loh, El‐Wui</au><au>Wu, Mei‐Yi</au><au>Chang, Yu‐Sheng</au><au>Tam, Ka‐Wai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials</atitle><jtitle>Pharmacotherapy</jtitle><addtitle>Pharmacotherapy</addtitle><date>2018-11</date><risdate>2018</risdate><volume>38</volume><issue>11</issue><spage>1106</spage><epage>1119</epage><pages>1106-1119</pages><issn>0277-0008</issn><eissn>1875-9114</eissn><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.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30246299</pmid><doi>10.1002/phar.2183</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-1994-834X</orcidid></addata></record> |
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| ispartof | Pharmacotherapy, 2018-11, Vol.38 (11), p.1106-1119 |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Allopurinol Clinical trials Gout Hyperuricemia lesinurad Meta-analysis Patients Randomization Rheumatism Safety Systematic review urate‐lowering therapy Uric acid uricosuric agent Xanthine oxidase |
| title | Efficacy and Safety of Lesinurad in Patients with Hyperuricemia Associated with Gout: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials |
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