Serum urate as surrogate endpoint for flares in people with gout: A systematic review and meta-regression analysis
The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials. Multiple...
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| Veröffentlicht in: | Seminars in arthritis and rheumatism 2018-10, Vol.48 (2), p.293-301 |
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| creator | Stamp, Lisa Morillon, Melanie B. Taylor, William J. Dalbeth, Nicola Singh, Jasvinder A. Lassere, Marissa Christensen, Robin |
| description | The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials.
Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers.
Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was |
| doi_str_mv | 10.1016/j.semarthrit.2018.02.009 |
| format | Article |
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Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers.
Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU.
Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data—including longer duration extension studies—SU < 6mg/dL was associated with reduced gout flares.</description><identifier>ISSN: 0049-0172</identifier><identifier>EISSN: 1532-866X</identifier><identifier>DOI: 10.1016/j.semarthrit.2018.02.009</identifier><identifier>PMID: 29566967</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Biomarker ; Biomarkers - blood ; Clinical Trials as Topic ; Gout ; Gout - blood ; Gout - diagnosis ; Gout - drug therapy ; Gout flares ; Gout Suppressants - therapeutic use ; Humans ; Serum urate ; Treatment Outcome ; Uric Acid - blood</subject><ispartof>Seminars in arthritis and rheumatism, 2018-10, Vol.48 (2), p.293-301</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-fb6e0cd3a5f5215db90e293712908400a40510df7db325298f623dd471b61a7b3</citedby><cites>FETCH-LOGICAL-c450t-fb6e0cd3a5f5215db90e293712908400a40510df7db325298f623dd471b61a7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.semarthrit.2018.02.009$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29566967$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stamp, Lisa</creatorcontrib><creatorcontrib>Morillon, Melanie B.</creatorcontrib><creatorcontrib>Taylor, William J.</creatorcontrib><creatorcontrib>Dalbeth, Nicola</creatorcontrib><creatorcontrib>Singh, Jasvinder A.</creatorcontrib><creatorcontrib>Lassere, Marissa</creatorcontrib><creatorcontrib>Christensen, Robin</creatorcontrib><title>Serum urate as surrogate endpoint for flares in people with gout: A systematic review and meta-regression analysis</title><title>Seminars in arthritis and rheumatism</title><addtitle>Semin Arthritis Rheum</addtitle><description>The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials.
Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers.
Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU.
Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data—including longer duration extension studies—SU < 6mg/dL was associated with reduced gout flares.</description><subject>Biomarker</subject><subject>Biomarkers - blood</subject><subject>Clinical Trials as Topic</subject><subject>Gout</subject><subject>Gout - blood</subject><subject>Gout - diagnosis</subject><subject>Gout - drug therapy</subject><subject>Gout flares</subject><subject>Gout Suppressants - therapeutic use</subject><subject>Humans</subject><subject>Serum urate</subject><subject>Treatment Outcome</subject><subject>Uric Acid - blood</subject><issn>0049-0172</issn><issn>1532-866X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEFv1DAQhS0EotvCX6h87CXp2EmcpLdSQYtUiQMgcbOceLL1KolTj0O1_x4vW-ixp9GM3ps38zHGBeQChLrc5YSTCfEhuJhLEE0OMgdo37CNqAqZNUr9ess2AGWbgajlCTsl2gEIoaB-z05kWynVqnrDwncM68TXYCJyQ5zWEPz20OBsF-_myAcf-DCagMTdzBf0y4j8ycUHvvVrvOLXnPYU0z3R9Tzgb4dP3MyWTxhNFnCbjOT8nGZm3JOjD-zdYEbCj8_1jP388vnHzV12_-326831fdaXFcRs6BRCbwtTDZUUle1aQNkWtZAtNCWAKaESYIfadoWsZNsMShbWlrXolDB1V5yxi-PeJfjHFSnqyVGP42hm9CvpAzeQApoiSZujtA-eKOCgl-AS4L0WoA_E9U6_EP_r1CB1Ip6s588pazeh_W_8hzgJPh0FmH5NcIKm3uHco3UB-6itd6-n_AGTA5kS</recordid><startdate>20181001</startdate><enddate>20181001</enddate><creator>Stamp, Lisa</creator><creator>Morillon, Melanie B.</creator><creator>Taylor, William J.</creator><creator>Dalbeth, Nicola</creator><creator>Singh, Jasvinder A.</creator><creator>Lassere, Marissa</creator><creator>Christensen, Robin</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20181001</creationdate><title>Serum urate as surrogate endpoint for flares in people with gout: A systematic review and meta-regression analysis</title><author>Stamp, Lisa ; Morillon, Melanie B. ; Taylor, William J. ; Dalbeth, Nicola ; Singh, Jasvinder A. ; Lassere, Marissa ; Christensen, Robin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-fb6e0cd3a5f5215db90e293712908400a40510df7db325298f623dd471b61a7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Biomarker</topic><topic>Biomarkers - blood</topic><topic>Clinical Trials as Topic</topic><topic>Gout</topic><topic>Gout - blood</topic><topic>Gout - diagnosis</topic><topic>Gout - drug therapy</topic><topic>Gout flares</topic><topic>Gout Suppressants - therapeutic use</topic><topic>Humans</topic><topic>Serum urate</topic><topic>Treatment Outcome</topic><topic>Uric Acid - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stamp, Lisa</creatorcontrib><creatorcontrib>Morillon, Melanie B.</creatorcontrib><creatorcontrib>Taylor, William J.</creatorcontrib><creatorcontrib>Dalbeth, Nicola</creatorcontrib><creatorcontrib>Singh, Jasvinder A.</creatorcontrib><creatorcontrib>Lassere, Marissa</creatorcontrib><creatorcontrib>Christensen, Robin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Seminars in arthritis and rheumatism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stamp, Lisa</au><au>Morillon, Melanie B.</au><au>Taylor, William J.</au><au>Dalbeth, Nicola</au><au>Singh, Jasvinder A.</au><au>Lassere, Marissa</au><au>Christensen, Robin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum urate as surrogate endpoint for flares in people with gout: A systematic review and meta-regression analysis</atitle><jtitle>Seminars in arthritis and rheumatism</jtitle><addtitle>Semin Arthritis Rheum</addtitle><date>2018-10-01</date><risdate>2018</risdate><volume>48</volume><issue>2</issue><spage>293</spage><epage>301</epage><pages>293-301</pages><issn>0049-0172</issn><eissn>1532-866X</eissn><abstract>The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials.
Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers.
Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU.
Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data—including longer duration extension studies—SU < 6mg/dL was associated with reduced gout flares.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29566967</pmid><doi>10.1016/j.semarthrit.2018.02.009</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarker Biomarkers - blood Clinical Trials as Topic Gout Gout - blood Gout - diagnosis Gout - drug therapy Gout flares Gout Suppressants - therapeutic use Humans Serum urate Treatment Outcome Uric Acid - blood |
| title | Serum urate as surrogate endpoint for flares in people with gout: A systematic review and meta-regression analysis |
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