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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, Fernando
dc.contributor.authorAfonso, Joana
dc.contributor.authorLopes, Susana
dc.contributor.authorCoelho, Rosa
dc.contributor.authorGonçalves, Raquel
dc.contributor.authorCaldeira, Paulo
dc.contributor.authorLago, Paula
dc.contributor.authorSousa, Helena Tavares
dc.contributor.authorRamos, Jaime
dc.contributor.authorGonçalves, Ana Rita
dc.contributor.authorMinistro, Paula
dc.contributor.authorRosa, Isadora
dc.contributor.authorVieira, Ana Isabel
dc.contributor.authorAndrade, PatrĂ­cia
dc.contributor.authorSoares, JoĂŁo-Bruno
dc.contributor.authorCarvalho, Diana
dc.contributor.authorSousa, Paula
dc.contributor.authorMeira, Tania
dc.contributor.authorLopes, Joanne
dc.contributor.authorMoleiro, Joana
dc.contributor.authorDias, ClĂĄudia Camila
dc.contributor.authorFalcĂŁo, Amilcar
dc.contributor.authorGeboes, Karel
dc.contributor.authorCarneiro, FĂĄtima
dc.date.accessioned2018-12-07T14:53:16Z
dc.date.available2018-12-07T14:53:16Z
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 (2.62 mu g/mL vs. 1.15 mu g/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 3 mu g/mL (HR = 0.119, p = 0.010), and increased for patients with fecal calprotectin (FC) level above 250 mu g/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. (C) 2017 The Authors. Published by Elsevier B.V.
dc.description.sponsorshipPortuguese IBD Group (GEDII - Grupo de Estudo da Doenca Inflamatoria Intestinal)
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.ebiom.2017.06.004
dc.identifier.issn2352-3964
dc.identifier.urihttp://hdl.handle.net/10400.1/11430
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier Science Bv
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectInflammatory-bowel-disease
dc.subjectFecal Calprotectin
dc.subjectMaintenance therapy
dc.subjectCrohns-disease
dc.subjectMetaanalysis
dc.subjectOutcomes
dc.subjectMarker
dc.subjectAssays
dc.subjectIndex
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 Escalation
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage130
oaire.citation.startPage123
oaire.citation.titleEBioMedicine
oaire.citation.volume21
person.familyNameCaldeira
person.familyNameSousa
person.givenNamePaulo
person.givenNameHelena Tavares
person.identifier.ciencia-id1112-F0B2-19A3
person.identifier.ciencia-idCF1F-1163-1C4A
person.identifier.orcid0000-0002-2404-6295
person.identifier.orcid0000-0002-6626-205X
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication3def3720-8982-4c46-801d-af640d508b59
relation.isAuthorOfPublication6b1d11dd-486f-4fb3-b41f-02e1cf6a5c2e
relation.isAuthorOfPublication.latestForDiscovery6b1d11dd-486f-4fb3-b41f-02e1cf6a5c2e

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