The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease
Identifieur interne : 000265 ( Ncbi/Merge ); précédent : 000264; suivant : 000266The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease
Auteurs : Niels Vande Casteele [Belgique, États-Unis, Canada] ; Reena Khanna [Canada] ; Barrett G. Levesque [États-Unis, Canada] ; Larry Stitt [Canada] ; G Y Zou [Canada] ; Sharat Singh [États-Unis] ; Steve Lockton [États-Unis] ; Scott Hauenstein [États-Unis] ; Linda Ohrmund [États-Unis] ; Gordon R. Greenberg [Canada] ; Paul J. Rutgeerts [Belgique] ; Ann Gils [Belgique] ; William J. Sandborn [États-Unis] ; Séverine Vermeire [Belgique] ; Brian G. Feagan [Canada]Source :
- Gut [ 0017-5749 ] ; 2014.
Abstract
Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab.
In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission.
Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission.
The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed.
Url:
DOI: 10.1136/gutjnl-2014-307883
PubMed: 25336114
PubMed Central: 4602247
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Greenberg</name><affiliation wicri:level="1"><nlm:aff id="af5"><institution>University of Toronto, Mount Sinai Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rutgeerts, Paul J" sort="Rutgeerts, Paul J" uniqKey="Rutgeerts P" first="Paul J" last="Rutgeerts">Paul J. Rutgeerts</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>KU Leuven Department of Clinical and Experimental Medicine, Leuven</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gils, Ann" sort="Gils, Ann" uniqKey="Gils A" first="Ann" last="Gils">Ann Gils</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sandborn, William J" sort="Sandborn, William J" uniqKey="Sandborn W" first="William J" last="Sandborn">William J. 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Feagan</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25336114</idno><idno type="pmc">4602247</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602247</idno><idno type="RBID">PMC:4602247</idno><idno type="doi">10.1136/gutjnl-2014-307883</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000040</idno><idno type="wicri:Area/Pmc/Curation">000040</idno><idno type="wicri:Area/Pmc/Checkpoint">000176</idno><idno type="wicri:Area/Ncbi/Merge">000265</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease</title><author><name sortKey="Vande Casteele, Niels" sort="Vande Casteele, Niels" uniqKey="Vande Casteele N" first="Niels" last="Vande Casteele">Niels Vande Casteele</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Division of Gastroenterology</addr-line>,<institution>University of California San Diego</institution>,<addr-line>La Jolla, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Khanna, Reena" sort="Khanna, Reena" uniqKey="Khanna R" first="Reena" last="Khanna">Reena Khanna</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Levesque, Barrett G" sort="Levesque, Barrett G" uniqKey="Levesque B" first="Barrett G" last="Levesque">Barrett G. Levesque</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Division of Gastroenterology</addr-line>,<institution>University of California San Diego</institution>,<addr-line>La Jolla, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stitt, Larry" sort="Stitt, Larry" uniqKey="Stitt L" first="Larry" last="Stitt">Larry Stitt</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zou, G Y" sort="Zou, G Y" uniqKey="Zou G" first="G Y" last="Zou">G Y Zou</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Singh, Sharat" sort="Singh, Sharat" uniqKey="Singh S" first="Sharat" last="Singh">Sharat Singh</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Prometheus Laboratories, Inc., San Diego, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lockton, Steve" sort="Lockton, Steve" uniqKey="Lockton S" first="Steve" last="Lockton">Steve Lockton</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Prometheus Laboratories, Inc., San Diego, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hauenstein, Scott" sort="Hauenstein, Scott" uniqKey="Hauenstein S" first="Scott" last="Hauenstein">Scott Hauenstein</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Prometheus Laboratories, Inc., San Diego, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ohrmund, Linda" sort="Ohrmund, Linda" uniqKey="Ohrmund L" first="Linda" last="Ohrmund">Linda Ohrmund</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Prometheus Laboratories, Inc., San Diego, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Greenberg, Gordon R" sort="Greenberg, Gordon R" uniqKey="Greenberg G" first="Gordon R" last="Greenberg">Gordon R. Greenberg</name><affiliation wicri:level="1"><nlm:aff id="af5"><institution>University of Toronto, Mount Sinai Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rutgeerts, Paul J" sort="Rutgeerts, Paul J" uniqKey="Rutgeerts P" first="Paul J" last="Rutgeerts">Paul J. Rutgeerts</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>KU Leuven Department of Clinical and Experimental Medicine, Leuven</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gils, Ann" sort="Gils, Ann" uniqKey="Gils A" first="Ann" last="Gils">Ann Gils</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sandborn, William J" sort="Sandborn, William J" uniqKey="Sandborn W" first="William J" last="Sandborn">William J. Sandborn</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Division of Gastroenterology</addr-line>,<institution>University of California San Diego</institution>,<addr-line>La Jolla, California</addr-line>,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vermeire, Severine" sort="Vermeire, Severine" uniqKey="Vermeire S" first="Séverine" last="Vermeire">Séverine Vermeire</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>KU Leuven Department of Clinical and Experimental Medicine, Leuven</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Feagan, Brian G" sort="Feagan, Brian G" uniqKey="Feagan B" first="Brian G" last="Feagan">Brian G. Feagan</name><affiliation wicri:level="1"><nlm:aff id="af3"><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Gut</title><idno type="ISSN">0017-5749</idno><idno type="eISSN">1468-3288</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Objective</title><p>Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab.</p></sec><sec><title>Design</title><p>In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission.</p></sec><sec><title>Results</title><p>Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission.</p></sec><sec><title>Conclusions</title><p>The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Baert, F" uniqKey="Baert F">F Baert</name></author><author><name sortKey="Noman, M" uniqKey="Noman M">M Noman</name></author><author><name sortKey="Vermeire, S" uniqKey="Vermeire S">S Vermeire</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Steenholdt, C" uniqKey="Steenholdt C">C Steenholdt</name></author><author><name sortKey="Bendtzen, K" uniqKey="Bendtzen K">K Bendtzen</name></author><author><name sortKey="Brynskov, J" uniqKey="Brynskov J">J Brynskov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vande Casteele, N" uniqKey="Vande Casteele N">N Vande Casteele</name></author><author><name sortKey="Gils, A" uniqKey="Gils A">A Gils</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Gut</journal-id><journal-id journal-id-type="iso-abbrev">Gut</journal-id><journal-id journal-id-type="hwp">gutjnl</journal-id><journal-id journal-id-type="publisher-id">gut</journal-id><journal-title-group><journal-title>Gut</journal-title></journal-title-group><issn pub-type="ppub">0017-5749</issn><issn pub-type="epub">1468-3288</issn><publisher><publisher-name>BMJ Publishing Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25336114</article-id><article-id pub-id-type="pmc">4602247</article-id><article-id pub-id-type="publisher-id">gutjnl-2014-307883</article-id><article-id pub-id-type="doi">10.1136/gutjnl-2014-307883</article-id><article-categories><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject></subj-group><subj-group subj-group-type="heading"><subject>Inflammatory Bowel Disease</subject></subj-group><series-title>Original article</series-title></article-categories><title-group><article-title>The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Vande Casteele</surname><given-names>Niels</given-names></name><xref ref-type="aff" rid="af1">1</xref><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Khanna</surname><given-names>Reena</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Levesque</surname><given-names>Barrett G</given-names></name><xref ref-type="aff" rid="af2">2</xref><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Stitt</surname><given-names>Larry</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Zou</surname><given-names>G Y</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib><contrib contrib-type="author"><name><surname>Singh</surname><given-names>Sharat</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lockton</surname><given-names>Steve</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Hauenstein</surname><given-names>Scott</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Ohrmund</surname><given-names>Linda</given-names></name><xref ref-type="aff" rid="af4">4</xref></contrib><contrib contrib-type="author"><name><surname>Greenberg</surname><given-names>Gordon R</given-names></name><xref ref-type="aff" rid="af5">5</xref></contrib><contrib contrib-type="author"><name><surname>Rutgeerts</surname><given-names>Paul J</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Gils</surname><given-names>Ann</given-names></name><xref ref-type="aff" rid="af1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sandborn</surname><given-names>William J</given-names></name><xref ref-type="aff" rid="af2">2</xref></contrib><contrib contrib-type="author"><name><surname>Vermeire</surname><given-names>Séverine</given-names></name><xref ref-type="aff" rid="af6">6</xref></contrib><contrib contrib-type="author"><name><surname>Feagan</surname><given-names>Brian G</given-names></name><xref ref-type="aff" rid="af3">3</xref></contrib></contrib-group><aff id="af1"><label>1</label><addr-line>KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven</addr-line>,<country>Belgium</country></aff><aff id="af2"><label>2</label><addr-line>Division of Gastroenterology</addr-line>,<institution>University of California San Diego</institution>,<addr-line>La Jolla, California</addr-line>,<country>USA</country></aff><aff id="af3"><label>3</label><institution>Robarts Clinical Trials, Western University</institution>,<addr-line>London, Ontario</addr-line>,<country>Canada</country></aff><aff id="af4"><label>4</label><addr-line>Prometheus Laboratories, Inc., San Diego, California</addr-line>,<country>USA</country></aff><aff id="af5"><label>5</label><institution>University of Toronto, Mount Sinai Hospital</institution>,<addr-line>Toronto, Ontario</addr-line>,<country>Canada</country></aff><aff id="af6"><label>6</label><addr-line>KU Leuven Department of Clinical and Experimental Medicine, Leuven</addr-line>,<country>Belgium</country></aff><author-notes><corresp><label>Correspondence to</label> Brian G Feagan, Department of Medicine, Robarts Research Institute, University of Western Ontario, PO Box 5015, 100 Perth Drive, London, Ontario N6A 5K8, Canada; <email>Brian.Feagan@robartsinc.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>10</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>21</day><month>10</month><year>2014</year></pub-date><volume>64</volume><issue>10</issue><fpage>1539</fpage><lpage>1545</lpage><history><date date-type="received"><day>20</day><month>6</month><year>2014</year></date><date date-type="rev-recd"><day>3</day><month>9</month><year>2014</year></date><date date-type="accepted"><day>26</day><month>9</month><year>2014</year></date></history><permissions><copyright-statement>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</copyright-statement><copyright-year>2015</copyright-year><license license-type="open-access"><license-p>This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link></license-p></license></permissions><self-uri xlink:title="pdf" xlink:href="gutjnl-2014-307883.pdf"></self-uri><abstract><sec><title>Objective</title><p>Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab.</p></sec><sec><title>Design</title><p>In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission.</p></sec><sec><title>Results</title><p>Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission.</p></sec><sec><title>Conclusions</title><p>The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed.</p></sec></abstract><kwd-group><kwd>CROHN'S DISEASE</kwd><kwd>INFLIXIMAB</kwd><kwd>PHARMACOKINETICS</kwd><kwd>PHARMACOLOGY</kwd><kwd>TNF</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>special-feature</meta-name><meta-value>unlocked</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Belgique</li><li>Canada</li><li>États-Unis</li></country></list><tree><country name="Belgique"><noRegion><name sortKey="Vande Casteele, Niels" sort="Vande Casteele, Niels" uniqKey="Vande Casteele N" first="Niels" last="Vande Casteele">Niels Vande Casteele</name></noRegion><name sortKey="Gils, Ann" sort="Gils, Ann" uniqKey="Gils A" first="Ann" last="Gils">Ann Gils</name><name sortKey="Rutgeerts, Paul J" sort="Rutgeerts, Paul J" uniqKey="Rutgeerts P" first="Paul J" last="Rutgeerts">Paul J. Rutgeerts</name><name sortKey="Vermeire, Severine" sort="Vermeire, Severine" uniqKey="Vermeire S" first="Séverine" last="Vermeire">Séverine Vermeire</name></country><country name="États-Unis"><noRegion><name sortKey="Vande Casteele, Niels" sort="Vande Casteele, Niels" uniqKey="Vande Casteele N" first="Niels" last="Vande Casteele">Niels Vande Casteele</name></noRegion><name sortKey="Hauenstein, Scott" sort="Hauenstein, Scott" uniqKey="Hauenstein S" first="Scott" last="Hauenstein">Scott Hauenstein</name><name sortKey="Levesque, Barrett G" sort="Levesque, Barrett G" uniqKey="Levesque B" first="Barrett G" last="Levesque">Barrett G. Levesque</name><name sortKey="Lockton, Steve" sort="Lockton, Steve" uniqKey="Lockton S" first="Steve" last="Lockton">Steve Lockton</name><name sortKey="Ohrmund, Linda" sort="Ohrmund, Linda" uniqKey="Ohrmund L" first="Linda" last="Ohrmund">Linda Ohrmund</name><name sortKey="Sandborn, William J" sort="Sandborn, William J" uniqKey="Sandborn W" first="William J" last="Sandborn">William J. Sandborn</name><name sortKey="Singh, Sharat" sort="Singh, Sharat" uniqKey="Singh S" first="Sharat" last="Singh">Sharat Singh</name></country><country name="Canada"><noRegion><name sortKey="Vande Casteele, Niels" sort="Vande Casteele, Niels" uniqKey="Vande Casteele N" first="Niels" last="Vande Casteele">Niels Vande Casteele</name></noRegion><name sortKey="Feagan, Brian G" sort="Feagan, Brian G" uniqKey="Feagan B" first="Brian G" last="Feagan">Brian G. Feagan</name><name sortKey="Greenberg, Gordon R" sort="Greenberg, Gordon R" uniqKey="Greenberg G" first="Gordon R" last="Greenberg">Gordon R. Greenberg</name><name sortKey="Khanna, Reena" sort="Khanna, Reena" uniqKey="Khanna R" first="Reena" last="Khanna">Reena Khanna</name><name sortKey="Levesque, Barrett G" sort="Levesque, Barrett G" uniqKey="Levesque B" first="Barrett G" last="Levesque">Barrett G. Levesque</name><name sortKey="Stitt, Larry" sort="Stitt, Larry" uniqKey="Stitt L" first="Larry" last="Stitt">Larry Stitt</name><name sortKey="Zou, G Y" sort="Zou, G Y" uniqKey="Zou G" first="G Y" last="Zou">G Y Zou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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