Pharmacokinetic Parameters of Infliximab Influence the Rate of Relapse After De‐Escalation in Adults With Inflammatory Bowel Diseases

This study aimed at exploring the link among individual concentrations, pharmacokinetic parameters, and the probability of relapse after de‐escalation in a real‐world prospective cohort of patients with inflammatory bowel disease (IBD) who underwent infliximab treatment de‐escalation. Ninety‐one pat...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2019-09, Vol.106 (3), p.605-615
Main Authors: Petitcollin, Antoine, Brochard, Charlène, Siproudhis, Laurent, Tron, Camille, Verdier, Marie‐Clémence, Lemaitre, Florian, Lucidarme, Camille, Bouguen, Guillaume, Bellissant, Éric
Format: Article
Language:English
Subjects:
Adult
C-Reactive Protein
Colitis, Ulcerative - drug therapy
Female
Gastrointestinal Agents - pharmacokinetics
Gastrointestinal Agents - therapeutic use
Humans
Immunology
Immunotherapy
Inflammatory Bowel Diseases - drug therapy
Inflammatory Bowel Diseases - epidemiology
Infliximab - pharmacokinetics
Infliximab - therapeutic use
Life Sciences
Male
Metabolic Clearance Rate
Middle Aged
Pharmaceutical sciences
Pharmacology
Proportional Hazards Models
Recurrence
Remission Induction
Time Factors
Tobacco Use - epidemiology
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Summary:This study aimed at exploring the link among individual concentrations, pharmacokinetic parameters, and the probability of relapse after de‐escalation in a real‐world prospective cohort of patients with inflammatory bowel disease (IBD) who underwent infliximab treatment de‐escalation. Ninety‐one patients were included. A time‐varying compartment model was used to estimate individual pharmacokinetic parameters and trough concentrations. A Cox model was implemented to explore the parameters influencing the probability of relapse after de‐escalation. Volume, clearance, and trough before and after de‐escalation were linked to the relapse risk at the univariate step. Independent predictors of relapse were tobacco use and/or ulcerative colitis (P = 0.0093), a higher C‐reactive protein (CRP; P = 0.00064), and an infliximab trough  5.7 μg/mL are eligible to de‐escalation, but infliximab pharmacokinetics is highly variable in time. Therefore, drug monitoring is mandatory after de‐escalation to maintain trough > 2.4 μg/mL. Clearance monitoring seems an appealing approach for patient selection and relapse prediction.
ISSN:0009-9236
1532-6535
DOI:10.1002/cpt.1429