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The influence of subclinical active inflammation on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients

2024-01-19Artigo científico Acesso aberto
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datacite.subject.sdg03:Saúde de Qualidade
datacite.subject.sdg09:Indústria, Inovação e Infraestruturas
datacite.subject.sdg12:Produção e Consumo Sustentáveis
dc.contributor.authorMagro, Fernando
dc.contributor.authorFernandes, Samuel
dc.contributor.authorPatita, Marta
dc.contributor.authorArroja, Bruno
dc.contributor.authorLago, Paula
dc.contributor.authorRosa, Isadora
dc.contributor.authorSousa, Helena Tavares
dc.contributor.authorMinistro, Paula
dc.contributor.authorMocanu, Irina
dc.contributor.authorVieira, Ana
dc.contributor.authorCastela, Joana
dc.contributor.authorMoleiro, Joana
dc.contributor.authorRoseira, Joana
dc.contributor.authorCancela, Eugénia
dc.contributor.authorSousa, Paula
dc.contributor.authorPortela, Francisco
dc.contributor.authorCorreia, Luís
dc.contributor.authorMoreira, Paula
dc.contributor.authorDias, Sandra
dc.contributor.authorAfonso, Joana
dc.contributor.authorDanese, Silvio
dc.contributor.authorPeyrin-Biroulet, Laurent
dc.contributor.authorVucicevic, Katarina M
dc.contributor.authorSantiago, Mafalda
dc.date.accessioned2026-04-14T12:04:19Z
dc.date.available2026-04-14T12:04:19Z
dc.date.issued2024-01-19
dc.description.abstractBackground and aims: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study’s primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. Methods: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. Results: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression. Conclusion: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.eng
dc.identifier.doi10.1093/ecco-jcc/jjae014
dc.identifier.eissn1876-4479
dc.identifier.issn1873-9946
dc.identifier.urihttp://hdl.handle.net/10400.1/28670
dc.language.isoeng
dc.peerreviewedyes
dc.publisherOxford University Press
dc.relation.ispartofJournal of Crohn's and Colitis
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectInflammatory bowel disease
dc.subjectPharmacokinetic model
dc.subjectInfliximab
dc.titleThe influence of subclinical active inflammation on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patientseng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue7
oaire.citation.titleJournal of Crohn's and Colitis
oaire.citation.volume18
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameSousa
person.familyNameRoseira
person.givenNameHelena Tavares
person.givenNameJoana
person.identifier.ciencia-idCF1F-1163-1C4A
person.identifier.orcid0000-0002-6626-205X
person.identifier.orcid0000-0002-5098-8729
relation.isAuthorOfPublication6b1d11dd-486f-4fb3-b41f-02e1cf6a5c2e
relation.isAuthorOfPublication077331f1-402e-455f-8e16-e475d62bc73a
relation.isAuthorOfPublication.latestForDiscovery6b1d11dd-486f-4fb3-b41f-02e1cf6a5c2e

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