Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn's Disease

Abstract Background and aim Objective and more rigorous therapeutic outcomes are emerging as novel targets in Crohn's disease (CD). We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods This...

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Veröffentlicht in:Inflammatory bowel diseases 2018-09, Vol.24 (10), p.2266-2271
Hauptverfasser: Papamichael, Konstantinos, Rakowsky, Shana, Rivera, Claudio, Cheifetz, Adam S, Osterman, Mark T
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container_end_page 2271
container_issue 10
container_start_page 2266
container_title Inflammatory bowel diseases
container_volume 24
creator Papamichael, Konstantinos
Rakowsky, Shana
Rivera, Claudio
Cheifetz, Adam S
Osterman, Mark T
description Abstract Background and aim Objective and more rigorous therapeutic outcomes are emerging as novel targets in Crohn's disease (CD). We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods This retrospective multicenter study involved consecutive CD patients treated with infliximab who had a serum C-reactive protein (CRP) measured within 1 week or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between January 2010 and June 2016. Biochemical remission was defined as a normal CRP (≤5 mg/L). Endoscopic remission was defined as absence of any mucosal break (ulceration or erosion) or for patients with an ileocolonic resection, a Rutgeerts score of ≤i1. Histologic remission was defined as absence of active inflammation. Results Seventy-one CRP levels and 96 colonoscopies from 110 CD patients were evaluated. Based on ROC analyses, infliximab concentration thresholds of 2.2, 9.7, and 9.8 μg/mL were found to be related with biochemical, endoscopic, and histologic remission, respectively. Multiple logistic regression analyses identified infliximab concentration ≥2.2 (OR 6.4; 95% CI, 1.5-27.1; P = 0.011), ≥9.7 (OR 3.6; 95% CI, 1.4-9; P = 0.006) and ≥9.8 μg/mL (OR 3.2; 95% CI, 1.3-7.9; P = 0.011) as variables independently associated with biochemical, endoscopic, and histologic remission, respectively. Conclusions This study showed that higher maintenance infliximab trough concentrations are associated with more favorable rates of biochemical, endoscopic, or histologic remission in CD patients and that infliximab concentrations may differ based on the treatment goal.
doi_str_mv 10.1093/ibd/izy132
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We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods This retrospective multicenter study involved consecutive CD patients treated with infliximab who had a serum C-reactive protein (CRP) measured within 1 week or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between January 2010 and June 2016. Biochemical remission was defined as a normal CRP (≤5 mg/L). Endoscopic remission was defined as absence of any mucosal break (ulceration or erosion) or for patients with an ileocolonic resection, a Rutgeerts score of ≤i1. Histologic remission was defined as absence of active inflammation. Results Seventy-one CRP levels and 96 colonoscopies from 110 CD patients were evaluated. Based on ROC analyses, infliximab concentration thresholds of 2.2, 9.7, and 9.8 μg/mL were found to be related with biochemical, endoscopic, and histologic remission, respectively. Multiple logistic regression analyses identified infliximab concentration ≥2.2 (OR 6.4; 95% CI, 1.5-27.1; P = 0.011), ≥9.7 (OR 3.6; 95% CI, 1.4-9; P = 0.006) and ≥9.8 μg/mL (OR 3.2; 95% CI, 1.3-7.9; P = 0.011) as variables independently associated with biochemical, endoscopic, and histologic remission, respectively. Conclusions This study showed that higher maintenance infliximab trough concentrations are associated with more favorable rates of biochemical, endoscopic, or histologic remission in CD patients and that infliximab concentrations may differ based on the treatment goal.</description><identifier>ISSN: 1078-0998</identifier><identifier>EISSN: 1536-4844</identifier><identifier>DOI: 10.1093/ibd/izy132</identifier><identifier>PMID: 29718327</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adolescent ; Adult ; Crohn Disease - blood ; Crohn Disease - drug therapy ; Crohn Disease - pathology ; Drug Monitoring - methods ; Female ; Follow-Up Studies ; Gastrointestinal Agents - blood ; Gastrointestinal Agents - therapeutic use ; Humans ; Infliximab - blood ; Infliximab - therapeutic use ; Male ; Original Clinical ; Prognosis ; Remission Induction ; Retrospective Studies ; ROC Curve ; Young Adult</subject><ispartof>Inflammatory bowel diseases, 2018-09, Vol.24 (10), p.2266-2271</ispartof><rights>2018 Crohn's &amp; Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 2018</rights><rights>2018 Crohn’s &amp; Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-917b7deb85d1d909491efc3c16c6fc7e8f9343b059e10c42763177d0f659e75a3</citedby><cites>FETCH-LOGICAL-c408t-917b7deb85d1d909491efc3c16c6fc7e8f9343b059e10c42763177d0f659e75a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29718327$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Papamichael, Konstantinos</creatorcontrib><creatorcontrib>Rakowsky, Shana</creatorcontrib><creatorcontrib>Rivera, Claudio</creatorcontrib><creatorcontrib>Cheifetz, Adam S</creatorcontrib><creatorcontrib>Osterman, Mark T</creatorcontrib><title>Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn's Disease</title><title>Inflammatory bowel diseases</title><addtitle>Inflamm Bowel Dis</addtitle><description>Abstract Background and aim Objective and more rigorous therapeutic outcomes are emerging as novel targets in Crohn's disease (CD). We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods This retrospective multicenter study involved consecutive CD patients treated with infliximab who had a serum C-reactive protein (CRP) measured within 1 week or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between January 2010 and June 2016. Biochemical remission was defined as a normal CRP (≤5 mg/L). Endoscopic remission was defined as absence of any mucosal break (ulceration or erosion) or for patients with an ileocolonic resection, a Rutgeerts score of ≤i1. Histologic remission was defined as absence of active inflammation. Results Seventy-one CRP levels and 96 colonoscopies from 110 CD patients were evaluated. Based on ROC analyses, infliximab concentration thresholds of 2.2, 9.7, and 9.8 μg/mL were found to be related with biochemical, endoscopic, and histologic remission, respectively. Multiple logistic regression analyses identified infliximab concentration ≥2.2 (OR 6.4; 95% CI, 1.5-27.1; P = 0.011), ≥9.7 (OR 3.6; 95% CI, 1.4-9; P = 0.006) and ≥9.8 μg/mL (OR 3.2; 95% CI, 1.3-7.9; P = 0.011) as variables independently associated with biochemical, endoscopic, and histologic remission, respectively. Conclusions This study showed that higher maintenance infliximab trough concentrations are associated with more favorable rates of biochemical, endoscopic, or histologic remission in CD patients and that infliximab concentrations may differ based on the treatment goal.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Crohn Disease - blood</subject><subject>Crohn Disease - drug therapy</subject><subject>Crohn Disease - pathology</subject><subject>Drug Monitoring - methods</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gastrointestinal Agents - blood</subject><subject>Gastrointestinal Agents - therapeutic use</subject><subject>Humans</subject><subject>Infliximab - blood</subject><subject>Infliximab - therapeutic use</subject><subject>Male</subject><subject>Original Clinical</subject><subject>Prognosis</subject><subject>Remission Induction</subject><subject>Retrospective Studies</subject><subject>ROC Curve</subject><subject>Young Adult</subject><issn>1078-0998</issn><issn>1536-4844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAURS1ERduBDR-AvEEg1FA7TmJ7g9QOLa1UhATD2nKcl4lRxk7thDJ8TL-1nqZUsEFe2PI9uu9dXYReUvKeEsmObd0c299byvIn6ICWrMoKURRP05twkREpxT46jPEHIXk68hnazyWnguX8AN2exOiN1aP1Dp_CeAPg8DcI0wZfura3v-xG13gV_LTu8NI7A24M93TEH6dg3Rp_1taN4HTS8KqDoIct1q7Bp9abDjbW6P4In7nGR-MHa47uxQsbR9_7tTX4a2Ji3M23Di-D79yb5G0j6AjP0V6r-wgvHu4F-n5-tlpeZFdfPl0uT64yUxAxZpLymjdQi7KhjSSykBRawwytTNUaDqKVrGA1KSVQYoqcV4xy3pC2Sj-81GyBPsy-w1RvoJlT9moIKX7YKq-t-ldxtlNr_1NxmsYl7wV6-2AQ_PUEcVQplIG-1w78FFVOGGNCiHKHvptRE3yMAdrHMZSoXaEqFarmQhP86u_FHtE_DSbg9Qz4afif0R2HFq2e</recordid><startdate>20180915</startdate><enddate>20180915</enddate><creator>Papamichael, Konstantinos</creator><creator>Rakowsky, Shana</creator><creator>Rivera, Claudio</creator><creator>Cheifetz, Adam S</creator><creator>Osterman, Mark T</creator><general>Oxford University Press</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><scope>5PM</scope></search><sort><creationdate>20180915</creationdate><title>Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn's Disease</title><author>Papamichael, Konstantinos ; Rakowsky, Shana ; Rivera, Claudio ; Cheifetz, Adam S ; Osterman, Mark T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-917b7deb85d1d909491efc3c16c6fc7e8f9343b059e10c42763177d0f659e75a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Crohn Disease - blood</topic><topic>Crohn Disease - drug therapy</topic><topic>Crohn Disease - pathology</topic><topic>Drug Monitoring - methods</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gastrointestinal Agents - blood</topic><topic>Gastrointestinal Agents - therapeutic use</topic><topic>Humans</topic><topic>Infliximab - blood</topic><topic>Infliximab - therapeutic use</topic><topic>Male</topic><topic>Original Clinical</topic><topic>Prognosis</topic><topic>Remission Induction</topic><topic>Retrospective Studies</topic><topic>ROC Curve</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Papamichael, Konstantinos</creatorcontrib><creatorcontrib>Rakowsky, Shana</creatorcontrib><creatorcontrib>Rivera, Claudio</creatorcontrib><creatorcontrib>Cheifetz, Adam S</creatorcontrib><creatorcontrib>Osterman, Mark T</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Inflammatory bowel diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Papamichael, Konstantinos</au><au>Rakowsky, Shana</au><au>Rivera, Claudio</au><au>Cheifetz, Adam S</au><au>Osterman, Mark T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn's Disease</atitle><jtitle>Inflammatory bowel diseases</jtitle><addtitle>Inflamm Bowel Dis</addtitle><date>2018-09-15</date><risdate>2018</risdate><volume>24</volume><issue>10</issue><spage>2266</spage><epage>2271</epage><pages>2266-2271</pages><issn>1078-0998</issn><eissn>1536-4844</eissn><abstract>Abstract Background and aim Objective and more rigorous therapeutic outcomes are emerging as novel targets in Crohn's disease (CD). We investigated the association between maintenance serum infliximab trough concentrations and biochemical, endoscopic, or histologic remission in CD. Methods This retrospective multicenter study involved consecutive CD patients treated with infliximab who had a serum C-reactive protein (CRP) measured within 1 week or endoscopic evaluation within 12 weeks of therapeutic drug monitoring between January 2010 and June 2016. Biochemical remission was defined as a normal CRP (≤5 mg/L). Endoscopic remission was defined as absence of any mucosal break (ulceration or erosion) or for patients with an ileocolonic resection, a Rutgeerts score of ≤i1. Histologic remission was defined as absence of active inflammation. Results Seventy-one CRP levels and 96 colonoscopies from 110 CD patients were evaluated. Based on ROC analyses, infliximab concentration thresholds of 2.2, 9.7, and 9.8 μg/mL were found to be related with biochemical, endoscopic, and histologic remission, respectively. Multiple logistic regression analyses identified infliximab concentration ≥2.2 (OR 6.4; 95% CI, 1.5-27.1; P = 0.011), ≥9.7 (OR 3.6; 95% CI, 1.4-9; P = 0.006) and ≥9.8 μg/mL (OR 3.2; 95% CI, 1.3-7.9; P = 0.011) as variables independently associated with biochemical, endoscopic, and histologic remission, respectively. Conclusions This study showed that higher maintenance infliximab trough concentrations are associated with more favorable rates of biochemical, endoscopic, or histologic remission in CD patients and that infliximab concentrations may differ based on the treatment goal.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>29718327</pmid><doi>10.1093/ibd/izy132</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Crohn Disease - blood
Crohn Disease - drug therapy
Crohn Disease - pathology
Drug Monitoring - methods
Female
Follow-Up Studies
Gastrointestinal Agents - blood
Gastrointestinal Agents - therapeutic use
Humans
Infliximab - blood
Infliximab - therapeutic use
Male
Original Clinical
Prognosis
Remission Induction
Retrospective Studies
ROC Curve
Young Adult
title Association Between Serum Infliximab Trough Concentrations During Maintenance Therapy and Biochemical, Endoscopic, and Histologic Remission in Crohn's Disease
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