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Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients
There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of...
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Published in: | Osteoarthritis and cartilage 2019-03, Vol.27 (3), p.484-492 |
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container_end_page | 492 |
container_issue | 3 |
container_start_page | 484 |
container_title | Osteoarthritis and cartilage |
container_volume | 27 |
creator | Karsdal, M.A. Verburg, K.M. West, C.R. Bay-Jensen, A.C. Keller, D.S. Arends, R.H.G.P. |
description | There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of patients.
The aim of this study was to phenotype with biochemical biomarkers of bone, cartilage, soft tissue, synovial metabolism OA patients who are at risk of developing RPOA type-2, for both limited and chronic NSAIDs users.
The dataset consisted of OA patients participating in tanezumab trials who used NSAIDs |
doi_str_mv | 10.1016/j.joca.2018.12.001 |
format | article |
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The aim of this study was to phenotype with biochemical biomarkers of bone, cartilage, soft tissue, synovial metabolism OA patients who are at risk of developing RPOA type-2, for both limited and chronic NSAIDs users.
The dataset consisted of OA patients participating in tanezumab trials who used NSAIDs <90 days (limited NSAID users) or chronic users (NSAIDs ≥90 days) over an average 10 month period. Biomarker data were available for 47 cases (RPOA type-2) and 92 controls. Non-linear and linear multivariable predictive models were developed.
By use of two biomarkers at baseline the receiver operating characteristic (ROC) curve area for RPOA type-2 in limited NSAID users was 71%, [CI] (60–83%). OA subjects with this biomarker phenotype had 8-fold higher confidence interval [CI][(2–33)] relative risk of developing RPOA type-2 as compared to OA patients without this phenotype. The AUC of the model in chronic NSAIDs users based on 5 biomarkers was 78%, [CI](69–88%), with 4-fold [CI (2–6)] relative risk of developing RPOA type-2.
In this hypothesis generating and exploratory study, we identified combinations of biomarkers associated with OA patients who develop RPOA type-2, which may be related to the pathology of the RPOA type-2 joint.</description><identifier>ISSN: 1063-4584</identifier><identifier>EISSN: 1522-9653</identifier><identifier>DOI: 10.1016/j.joca.2018.12.001</identifier><identifier>PMID: 30576794</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Biomarker ; Clinical study ; Osteoarthritis ; RPOA2 ; THR</subject><ispartof>Osteoarthritis and cartilage, 2019-03, Vol.27 (3), p.484-492</ispartof><rights>2018</rights><rights>Copyright © 2018. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-4c6d36dac36eb339409db78fc09b65f107b1575288ff51f29df8b86794fc732c3</citedby><cites>FETCH-LOGICAL-c400t-4c6d36dac36eb339409db78fc09b65f107b1575288ff51f29df8b86794fc732c3</cites><orcidid>0000-0002-4764-5100 ; 0000-0001-7952-9297</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30576794$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karsdal, M.A.</creatorcontrib><creatorcontrib>Verburg, K.M.</creatorcontrib><creatorcontrib>West, C.R.</creatorcontrib><creatorcontrib>Bay-Jensen, A.C.</creatorcontrib><creatorcontrib>Keller, D.S.</creatorcontrib><creatorcontrib>Arends, R.H.G.P.</creatorcontrib><title>Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients</title><title>Osteoarthritis and cartilage</title><addtitle>Osteoarthritis Cartilage</addtitle><description>There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of patients.
The aim of this study was to phenotype with biochemical biomarkers of bone, cartilage, soft tissue, synovial metabolism OA patients who are at risk of developing RPOA type-2, for both limited and chronic NSAIDs users.
The dataset consisted of OA patients participating in tanezumab trials who used NSAIDs <90 days (limited NSAID users) or chronic users (NSAIDs ≥90 days) over an average 10 month period. Biomarker data were available for 47 cases (RPOA type-2) and 92 controls. Non-linear and linear multivariable predictive models were developed.
By use of two biomarkers at baseline the receiver operating characteristic (ROC) curve area for RPOA type-2 in limited NSAID users was 71%, [CI] (60–83%). OA subjects with this biomarker phenotype had 8-fold higher confidence interval [CI][(2–33)] relative risk of developing RPOA type-2 as compared to OA patients without this phenotype. The AUC of the model in chronic NSAIDs users based on 5 biomarkers was 78%, [CI](69–88%), with 4-fold [CI (2–6)] relative risk of developing RPOA type-2.
In this hypothesis generating and exploratory study, we identified combinations of biomarkers associated with OA patients who develop RPOA type-2, which may be related to the pathology of the RPOA type-2 joint.</description><subject>Biomarker</subject><subject>Clinical study</subject><subject>Osteoarthritis</subject><subject>RPOA2</subject><subject>THR</subject><issn>1063-4584</issn><issn>1522-9653</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kEtLJDEURoM4-Br_gAuppZuquUkq9QA3Ir5AmMXMrEMeN5q2utMmacH59abo1qWrXMK5H_c7hJxRaCjQ7teiWQSjGgZ0aChrAOgeOaKCsXrsBN8vM3S8bsXQHpLjlBYAwCmFA3LIQfRdP7ZHRP_BGKbw5I2aKu3DUsUXjNU6BucnTFVwVVRrb6f3-e8pYkr-DauQMgYV83P02afKr6qsVvh_s1S6zhFVRlutVfa4yukn-eHUlPB0956Qf7c3f6_v68ffdw_XV4-1aQFy3ZrO8s4qwzvUnI8tjFb3gzMw6k44Cr2mohdsGJwT1LHRukEPcwtnes4MPyEX29xy6OsGU5ZLnwxOU7ksbJJkVIzjUPi2oGyLmhhSiujkOvpS_V1SkLNbuZCzWzm7lZTJ4rYsne_yN3qJ9mvlU2YBLrcAlpZvHqNMphgwaH1Ek6UN_rv8D8eFjOM</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Karsdal, M.A.</creator><creator>Verburg, K.M.</creator><creator>West, C.R.</creator><creator>Bay-Jensen, A.C.</creator><creator>Keller, D.S.</creator><creator>Arends, R.H.G.P.</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4764-5100</orcidid><orcidid>https://orcid.org/0000-0001-7952-9297</orcidid></search><sort><creationdate>20190301</creationdate><title>Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients</title><author>Karsdal, M.A. ; Verburg, K.M. ; West, C.R. ; Bay-Jensen, A.C. ; Keller, D.S. ; Arends, R.H.G.P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-4c6d36dac36eb339409db78fc09b65f107b1575288ff51f29df8b86794fc732c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Biomarker</topic><topic>Clinical study</topic><topic>Osteoarthritis</topic><topic>RPOA2</topic><topic>THR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karsdal, M.A.</creatorcontrib><creatorcontrib>Verburg, K.M.</creatorcontrib><creatorcontrib>West, C.R.</creatorcontrib><creatorcontrib>Bay-Jensen, A.C.</creatorcontrib><creatorcontrib>Keller, D.S.</creatorcontrib><creatorcontrib>Arends, R.H.G.P.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Osteoarthritis and cartilage</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karsdal, M.A.</au><au>Verburg, K.M.</au><au>West, C.R.</au><au>Bay-Jensen, A.C.</au><au>Keller, D.S.</au><au>Arends, R.H.G.P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients</atitle><jtitle>Osteoarthritis and cartilage</jtitle><addtitle>Osteoarthritis Cartilage</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>27</volume><issue>3</issue><spage>484</spage><epage>492</epage><pages>484-492</pages><issn>1063-4584</issn><eissn>1522-9653</eissn><abstract>There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of patients.
The aim of this study was to phenotype with biochemical biomarkers of bone, cartilage, soft tissue, synovial metabolism OA patients who are at risk of developing RPOA type-2, for both limited and chronic NSAIDs users.
The dataset consisted of OA patients participating in tanezumab trials who used NSAIDs <90 days (limited NSAID users) or chronic users (NSAIDs ≥90 days) over an average 10 month period. Biomarker data were available for 47 cases (RPOA type-2) and 92 controls. Non-linear and linear multivariable predictive models were developed.
By use of two biomarkers at baseline the receiver operating characteristic (ROC) curve area for RPOA type-2 in limited NSAID users was 71%, [CI] (60–83%). OA subjects with this biomarker phenotype had 8-fold higher confidence interval [CI][(2–33)] relative risk of developing RPOA type-2 as compared to OA patients without this phenotype. The AUC of the model in chronic NSAIDs users based on 5 biomarkers was 78%, [CI](69–88%), with 4-fold [CI (2–6)] relative risk of developing RPOA type-2.
In this hypothesis generating and exploratory study, we identified combinations of biomarkers associated with OA patients who develop RPOA type-2, which may be related to the pathology of the RPOA type-2 joint.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>30576794</pmid><doi>10.1016/j.joca.2018.12.001</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-4764-5100</orcidid><orcidid>https://orcid.org/0000-0001-7952-9297</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biomarker Clinical study Osteoarthritis RPOA2 THR |
title | Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients |
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