Pharmacokinetic Parameters of Infliximab Influence the Rate of Relapse After De‐Escalation in Adults With Inflammatory Bowel Diseases. Issue 3 (29th April 2019)

• Record Type: Journal Article
• Authors: Petitcollin, Antoine; Brochard, Charlène; Siproudhis, Laurent; Tron, Camille; Verdier, Marie‐Clémence; Lemaitre, Florian; Lucidarme, Camille; Bouguen, Guillaume; Bellissant, Éric
• Is Part Of: Clinical pharmacology & therapeutics. Volume 106:Issue 3(2019)
• Page Start: 605
• Page End: 615
• Publication Date: 2019-04-29
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.1429
• Languages: English
• ISSNs: 0009-9236

Abstract

Abstract : 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 < 2.4 μg/mL after de‐escalation ( P = 0.0001). Patients with 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.