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.

التفاصيل البيبلوغرافية
العنوان:	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.
المؤلفون:	Magro F; Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.; Department of Gastroenterology, São João Hospital University Centre, Porto, Portugal.; Centre for Health Technology and Services Research, Health Research Network (CINTESIS@RISE), Faculty of Medicine of the University of Porto, Portugal.; Clinical Pharmacology Unit, São João Hospital University Centre, Porto, Portugal.; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal., Fernandes S; Department of Gastroenterology, Northern Lisbon University Hospital Centre, Lisbon, Portugal.; Clinica Universitária de Gastrenterologia da Universidade de Medicina de Lisboa, Lisbon, Portugal., Patita M; Department of Gastroenterology, Garcia da Orta Hospital, Almada, Portugal., Arroja B; Department of Gastroenterology, Braga Hospital, Braga, Portugal., Lago P; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal.; Department of Gastroenterology, Porto Hospital University Centre, Porto, Portugal., Rosa I; Department of Gastroenterology, IPOLFG, EPE, Lisbon, Portugal., Tavares de Sousa H; Department of Gastroenterology, Algarve Hospital University Centre - Portimão Unit, Portimão, Portugal.; ABC - Algarve Biomedical Center, University of Algarve, Faro, Portugal., Ministro P; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal.; Department of Gastroenterology, Viseu-Tondela Hospital Centre, Viseu, Portugal., Mocanu I; Department of Gastroenterology, Garcia da Orta Hospital, Almada, Portugal., Vieira A; Department of Gastroenterology, Garcia da Orta Hospital, Almada, Portugal., Castela J; Department of Gastroenterology, IPOLFG, EPE, Lisbon, Portugal., Moleiro J; Department of Gastroenterology, IPOLFG, EPE, Lisbon, Portugal., Roseira J; Department of Gastroenterology, Algarve Hospital University Centre - Portimão Unit, Portimão, Portugal.; ABC - Algarve Biomedical Center, University of Algarve, Faro, Portugal., Cancela E; Department of Gastroenterology, Viseu-Tondela Hospital Centre, Viseu, Portugal., Sousa P; Department of Gastroenterology, Viseu-Tondela Hospital Centre, Viseu, Portugal., Portela F; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal.; Department of Gastroenterology, Coimbra Hospital University Centre, Coimbra, Portugal., Correia L; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal.; Department of Gastroenterology, Northern Lisbon University Hospital Centre, Lisbon, Portugal., Moreira P; Clinical Pharmacology Unit, São João Hospital University Centre, Porto, Portugal., Dias S; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal., Afonso J; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal., Danese S; Department of Biomedical Sciences, Humanitas University, Milan, Italy.; IBD Center, Humanitas Research Hospital, IRCCS, Milan, Italy., Peyrin-Biroulet L; Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Nancy, France., Vucicevic KM; Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade, Serbia., Santiago M; Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doença Inflamatória Intestinal - GEDII), Porto, Portugal.
المصدر:	Journal of Crohn's & colitis [J Crohns Colitis] 2024 Aug 06; Vol. 18 (7), pp. 1102-1112.
نوع المنشور:	Journal Article; Multicenter Study
اللغة:	English
بيانات الدورية:	Publisher: Oxford University Press Country of Publication: England NLM ID: 101318676 Publication Model: Print Cited Medium: Internet ISSN: 1876-4479 (Electronic) Linking ISSN: 18739946 NLM ISO Abbreviation: J Crohns Colitis Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2015- : Oxford : Oxford University Press Original Publication: Amsterdam : Elsevier Science
مواضيع طبية MeSH:	Infliximab/pharmacokinetics , Disease Progression , Leukocyte L1 Antigen Complex/analysis , Inflammatory Bowel Diseases/drug therapy , Gastrointestinal Agents/pharmacokinetics , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents*/blood, Humans ; Male ; Female ; Prospective Studies ; Adult ; Middle Aged ; Feces/chemistry ; Body Weight ; Colitis, Ulcerative/drug therapy
مستخلص:	Background 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. (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
معلومات مُعتمدة:	Portuguese Study Group in Inflammatory Bowel Disease (GEDII)
فهرسة مساهمة:	Keywords: inflammatory bowel disease; infliximab; pharmacokinetic model
المشرفين على المادة:	B72HH48FLU (Infliximab) 0 (Leukocyte L1 Antigen Complex) 0 (Gastrointestinal Agents)
تواريخ الأحداث:	Date Created: 20240120 Date Completed: 20240806 Latest Revision: 20240806
رمز التحديث:	20240807
DOI:	10.1093/ecco-jcc/jjae014
PMID:	38243908
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1876-4479
DOI:	10.1093/ecco-jcc/jjae014