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Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation

2017-07Journal article Open access
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dc.contributor.authorMagro, F.
dc.contributor.authorAfonso, J.
dc.contributor.authorLopes, S.
dc.contributor.authorCoelho, R.
dc.contributor.authorGonçalves, R.
dc.contributor.authorCaldeira, P.
dc.contributor.authorLago, P.
dc.contributor.authorSousa, H.
dc.contributor.authorRamos, J.
dc.contributor.authorGonçalves, A.
dc.contributor.authorMinistro, P.
dc.contributor.authorRosa, I.
dc.contributor.authorVieira, A.
dc.contributor.authorAndrade, P.
dc.contributor.authorSoares, J.
dc.contributor.authorCarvalho, D.
dc.contributor.authorSousa, P.
dc.contributor.authorMeira, T.
dc.contributor.authorLopes, J.
dc.contributor.authorMoleiro, J.
dc.contributor.authorDias, C.
dc.contributor.authorFalcão, A.
dc.contributor.authorGeboes, K.
dc.contributor.authorCarneiro, F.
dc.date.accessioned2018-08-23T08:46:32Z
dc.date.available2018-08-23T08:46:32Z
dc.date.issued2017-07
dc.description.abstractAlthough infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62μg/mL vs. 1.15μg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3μg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250μg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.pt_PT
dc.description.sponsorshipThis work was supported by the Portuguese IBD Group (GEDII – Grupo de Estudo da Doença Inflamatória Intestinal). The funder had no role in study design, data collection, data analysis, interpretation and writing of the report.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEBioMedicine. 2017 Jul;21:123-130pt_PT
dc.identifier.doi10.1016/j.ebiom.2017.06.004pt_PT
dc.identifier.issn2352-3964
dc.identifier.urihttp://hdl.handle.net/10400.16/2220
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2352396417302323?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAntibodies to infliximabpt_PT
dc.subjectFecal calprotectinpt_PT
dc.subjectTherapeutic escalationpt_PT
dc.subjectUlcerative colitispt_PT
dc.titleCalprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceNetherlandspt_PT
oaire.citation.endPage130pt_PT
oaire.citation.startPage123pt_PT
oaire.citation.titleEBioMedicinept_PT
oaire.citation.volume21pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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