Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial
Identifieur interne : 000226 ( Main/Exploration ); précédent : 000225; suivant : 000227Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial
Auteurs : Freddy Cornillie [Pays-Bas] ; Stephen B. Hanauer [États-Unis] ; Robert H. Diamond [États-Unis] ; Jianping Wang [États-Unis] ; Kezhen L. Tang [États-Unis] ; Zhenhua Xu [États-Unis] ; Paul Rutgeerts [Belgique] ; Séverine Vermeire [Belgique]Source :
- Gut [ 0017-5749 ] ; 2014.
Abstract
Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment.
To carry out a post hoc analysis of A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I (ACCENT I) to evaluate the association between serum infliximab trough levels and C-reactive protein (CRP) after 14 weeks of induction treatment with durable sustained long-term response (Crohn's Disease Activity Index decrease ≥70 points and reduction ≥25% from baseline).
ACCENT I was a multicentre, randomised, placebo-controlled study. Week 14 trough levels and CRP percentage decrease from baseline to week 14 were compared between patients with and without durable sustained response through week 54. Sensitivity and specificity were determined to predict durable sustained response. Receiver operating characteristic (ROC) curves identified optimal cut-off points; logistic regression determined ORs.
After induction with 5 mg/kg infliximab, 25% (37/147) and 33% (47/144) of patients sustained week 14 response to infliximab 5 or 10 mg/kg, respectively, administered every 8 weeks without dose escalation, through week 54. Median week 14 trough levels of patients with and without durable sustained response to infliximab 5 mg/kg were 4.0 and 1.9 μg/mL, respectively (p=0.0331). Optimal predictors of durable sustained response to maintenance infliximab 5 mg/kg were week 14 trough level ≥3.5 µg/mL and ≥60% CRP decrease (ORs (95% CI), 3.5 (1.1 to 11.4) and 7.3 (1.4 to 36.7)), respectively, in patients with raised baseline CRP (>8.0 mg/L); area under the ROC curve was 0.75 for both predictors. A ≥3.5 µg/mL week 14 infliximab serum level did not predict durable sustained response to 10 mg/kg maintenance infliximab.
Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher postinduction trough levels than patients without durable sustained response. Serum infliximab trough levels ≥3.5 µg/mL and ≥60% CRP decrease were significantly associated with durable sustained response.
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DOI: 10.1136/gutjnl-2012-304094
PubMed: 24474383
PubMed Central: 4215276
Affiliations:
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Hanauer</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Departments of Gastroenterology, Hepatology, and Nutrition</addr-line>,<institution>The University of Chicago Medicine</institution>,<addr-line>Chicago, Illinois</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="Diamond, Robert H" sort="Diamond, Robert H" uniqKey="Diamond R" first="Robert H" last="Diamond">Robert H. Diamond</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Medical Group</addr-line>,<institution>Janssen Biotech, Inc</institution>,<addr-line>Horsham, Pennsylvania</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="Wang, Jianping" sort="Wang, Jianping" uniqKey="Wang J" first="Jianping" last="Wang">Jianping Wang</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Biostatistics and Programming, Janssen Research & Development</addr-line>,<institution>LLC</institution>,<addr-line>Horsham, Pennsylvania</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="Tang, Kezhen L" sort="Tang, Kezhen L" uniqKey="Tang K" first="Kezhen L" last="Tang">Kezhen L. Tang</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Biostatistics and Programming, Janssen Research & Development</addr-line>,<institution>LLC</institution>,<addr-line>Horsham, Pennsylvania</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="Xu, Zhenhua" sort="Xu, Zhenhua" uniqKey="Xu Z" first="Zhenhua" last="Xu">Zhenhua Xu</name><affiliation wicri:level="1"><nlm:aff id="af5"><addr-line>Biologics Clinical Pharmacology, Janssen Research & Development</addr-line>,<institution>LLC</institution>,<addr-line>Spring House, Pennsylvania</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="Rutgeerts, Paul" sort="Rutgeerts, Paul" uniqKey="Rutgeerts P" first="Paul" last="Rutgeerts">Paul Rutgeerts</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Department of Gastroenterology</addr-line>,<institution>University Hospital Gasthuisberg</institution>,<addr-line>KU 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="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>Department of Gastroenterology</addr-line>,<institution>University Hospital Gasthuisberg</institution>,<addr-line>KU 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="af7"><institution>National Fund for Scientific Research (FWO)</institution>,<addr-line>Flanders</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24474383</idno><idno type="pmc">4215276</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215276</idno><idno type="RBID">PMC:4215276</idno><idno type="doi">10.1136/gutjnl-2012-304094</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000368</idno><idno type="wicri:Area/Pmc/Curation">000368</idno><idno type="wicri:Area/Pmc/Checkpoint">000191</idno><idno type="wicri:Area/Ncbi/Merge">000219</idno><idno type="wicri:Area/Ncbi/Curation">000219</idno><idno type="wicri:Area/Ncbi/Checkpoint">000219</idno><idno type="wicri:doubleKey">0017-5749:2014:Cornillie F:postinduction:serum:infliximab</idno><idno type="wicri:Area/Main/Merge">000226</idno><idno type="wicri:Area/Main/Curation">000226</idno><idno type="wicri:Area/Main/Exploration">000226</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial</title><author><name sortKey="Cornillie, Freddy" sort="Cornillie, Freddy" uniqKey="Cornillie F" first="Freddy" last="Cornillie">Freddy Cornillie</name><affiliation wicri:level="1"><nlm:aff id="af1"><addr-line>Department of Immunology</addr-line>,<institution>Janssen Biologics BV</institution>,<addr-line>Leiden</addr-line>,<country>The Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hanauer, Stephen B" sort="Hanauer, Stephen B" uniqKey="Hanauer S" first="Stephen B" last="Hanauer">Stephen B. Hanauer</name><affiliation wicri:level="1"><nlm:aff id="af2"><addr-line>Departments of Gastroenterology, Hepatology, and Nutrition</addr-line>,<institution>The University of Chicago Medicine</institution>,<addr-line>Chicago, Illinois</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="Diamond, Robert H" sort="Diamond, Robert H" uniqKey="Diamond R" first="Robert H" last="Diamond">Robert H. Diamond</name><affiliation wicri:level="1"><nlm:aff id="af3"><addr-line>Medical Group</addr-line>,<institution>Janssen Biotech, Inc</institution>,<addr-line>Horsham, Pennsylvania</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="Wang, Jianping" sort="Wang, Jianping" uniqKey="Wang J" first="Jianping" last="Wang">Jianping Wang</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Biostatistics and Programming, Janssen Research & Development</addr-line>,<institution>LLC</institution>,<addr-line>Horsham, Pennsylvania</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="Tang, Kezhen L" sort="Tang, Kezhen L" uniqKey="Tang K" first="Kezhen L" last="Tang">Kezhen L. Tang</name><affiliation wicri:level="1"><nlm:aff id="af4"><addr-line>Biostatistics and Programming, Janssen Research & Development</addr-line>,<institution>LLC</institution>,<addr-line>Horsham, Pennsylvania</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="Xu, Zhenhua" sort="Xu, Zhenhua" uniqKey="Xu Z" first="Zhenhua" last="Xu">Zhenhua Xu</name><affiliation wicri:level="1"><nlm:aff id="af5"><addr-line>Biologics Clinical Pharmacology, Janssen Research & Development</addr-line>,<institution>LLC</institution>,<addr-line>Spring House, Pennsylvania</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="Rutgeerts, Paul" sort="Rutgeerts, Paul" uniqKey="Rutgeerts P" first="Paul" last="Rutgeerts">Paul Rutgeerts</name><affiliation wicri:level="1"><nlm:aff id="af6"><addr-line>Department of Gastroenterology</addr-line>,<institution>University Hospital Gasthuisberg</institution>,<addr-line>KU 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="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>Department of Gastroenterology</addr-line>,<institution>University Hospital Gasthuisberg</institution>,<addr-line>KU 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="af7"><institution>National Fund for Scientific Research (FWO)</institution>,<addr-line>Flanders</addr-line>,<country>Belgium</country></nlm:aff><country xml:lang="fr">Belgique</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>Background</title><p>Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment.</p></sec><sec><title>Objective</title><p>To carry out a post hoc analysis of A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I (ACCENT I) to evaluate the association between serum infliximab trough levels and C-reactive protein (CRP) after 14 weeks of induction treatment with durable sustained long-term response (Crohn's Disease Activity Index decrease ≥70 points and reduction ≥25% from baseline).</p></sec><sec><title>Design</title><p>ACCENT I was a multicentre, randomised, placebo-controlled study. Week 14 trough levels and CRP percentage decrease from baseline to week 14 were compared between patients with and without durable sustained response through week 54. Sensitivity and specificity were determined to predict durable sustained response. Receiver operating characteristic (ROC) curves identified optimal cut-off points; logistic regression determined ORs.</p></sec><sec><title>Results</title><p>After induction with 5 mg/kg infliximab, 25% (37/147) and 33% (47/144) of patients sustained week 14 response to infliximab 5 or 10 mg/kg, respectively, administered every 8 weeks without dose escalation, through week 54. Median week 14 trough levels of patients with and without durable sustained response to infliximab 5 mg/kg were 4.0 and 1.9 μg/mL, respectively (p=0.0331). Optimal predictors of durable sustained response to maintenance infliximab 5 mg/kg were week 14 trough level ≥3.5 µg/mL and ≥60% CRP decrease (ORs (95% CI), 3.5 (1.1 to 11.4) and 7.3 (1.4 to 36.7)), respectively, in patients with raised baseline CRP (>8.0 mg/L); area under the ROC curve was 0.75 for both predictors. A ≥3.5 µg/mL week 14 infliximab serum level did not predict durable sustained response to 10 mg/kg maintenance infliximab.</p></sec><sec><title>Conclusions</title><p>Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher postinduction trough levels than patients without durable sustained response. Serum infliximab trough levels ≥3.5 µg/mL and ≥60% CRP decrease were significantly associated with durable sustained response.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hanauer, Sb" uniqKey="Hanauer S">SB Hanauer</name></author><author><name sortKey="Feagan, Bg" uniqKey="Feagan B">BG Feagan</name></author><author><name sortKey="Lichtenstein, Gr" uniqKey="Lichtenstein G">GR Lichtenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ben Horin, S" uniqKey="Ben Horin S">S Ben-Horin</name></author><author><name sortKey="Chowers, Y" uniqKey="Chowers Y">Y Chowers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maser, Ea" uniqKey="Maser E">EA Maser</name></author><author><name sortKey="Villela, R" uniqKey="Villela R">R Villela</name></author><author><name sortKey="Silverberg, Ms" uniqKey="Silverberg M">MS Silverberg</name></author></analytic></biblStruct><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="Rutgeerts, P" uniqKey="Rutgeerts P">P Rutgeerts</name></author><author><name sortKey="Feagan, Bg" uniqKey="Feagan B">BG Feagan</name></author><author><name sortKey="Lichtenstein, Gr" uniqKey="Lichtenstein G">GR Lichtenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanauer, Sb" uniqKey="Hanauer S">SB Hanauer</name></author><author><name sortKey="Wagner, Cl" uniqKey="Wagner C">CL Wagner</name></author><author><name sortKey="Bala, M" uniqKey="Bala M">M Bala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reinisch, W" uniqKey="Reinisch W">W Reinisch</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Oddens, Bj" uniqKey="Oddens B">BJ Oddens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jurgens, M" uniqKey="Jurgens M">M Jürgens</name></author><author><name sortKey="Mahachie John, Jm" uniqKey="Mahachie John J">JM Mahachie John</name></author><author><name sortKey="Cleynen, I" uniqKey="Cleynen I">I Cleynen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cornillie, F" uniqKey="Cornillie F">F Cornillie</name></author><author><name sortKey="Hanauer, Sb" uniqKey="Hanauer S">SB Hanauer</name></author><author><name sortKey="Diamond, Rh" uniqKey="Diamond R">RH Diamond</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schnitzler, F" uniqKey="Schnitzler F">F Schnitzler</name></author><author><name sortKey="Fidder, H" uniqKey="Fidder H">H Fidder</name></author><author><name sortKey="Ferrante, M" uniqKey="Ferrante M">M Ferrante</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arias, Mt" uniqKey="Arias M">MT Arias</name></author><author><name sortKey="Vande Casteele, N" uniqKey="Vande Casteele N">N Vande Casteele</name></author><author><name sortKey="Drobne, D" uniqKey="Drobne D">D Drobne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Colombel, Jf" uniqKey="Colombel J">JF Colombel</name></author><author><name sortKey="Sandborn, Wj" uniqKey="Sandborn W">WJ Sandborn</name></author><author><name sortKey="Reinisch, W" uniqKey="Reinisch W">W Reinisch</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Belgique</li><li>Pays-Bas</li><li>États-Unis</li></country></list><tree><country name="Pays-Bas"><noRegion><name sortKey="Cornillie, Freddy" sort="Cornillie, Freddy" uniqKey="Cornillie F" first="Freddy" last="Cornillie">Freddy Cornillie</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Hanauer, Stephen B" sort="Hanauer, Stephen B" uniqKey="Hanauer S" first="Stephen B" last="Hanauer">Stephen B. Hanauer</name></noRegion><name sortKey="Diamond, Robert H" sort="Diamond, Robert H" uniqKey="Diamond R" first="Robert H" last="Diamond">Robert H. Diamond</name><name sortKey="Tang, Kezhen L" sort="Tang, Kezhen L" uniqKey="Tang K" first="Kezhen L" last="Tang">Kezhen L. Tang</name><name sortKey="Wang, Jianping" sort="Wang, Jianping" uniqKey="Wang J" first="Jianping" last="Wang">Jianping Wang</name><name sortKey="Xu, Zhenhua" sort="Xu, Zhenhua" uniqKey="Xu Z" first="Zhenhua" last="Xu">Zhenhua Xu</name></country><country name="Belgique"><noRegion><name sortKey="Rutgeerts, Paul" sort="Rutgeerts, Paul" uniqKey="Rutgeerts P" first="Paul" last="Rutgeerts">Paul Rutgeerts</name></noRegion><name sortKey="Vermeire, Severine" sort="Vermeire, Severine" uniqKey="Vermeire S" first="Séverine" last="Vermeire">Séverine Vermeire</name><name sortKey="Vermeire, Severine" sort="Vermeire, Severine" uniqKey="Vermeire S" first="Séverine" last="Vermeire">Séverine Vermeire</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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