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

• DOI: 10.1002/cpt.1429
• Publication Date: 2019-03-12T14:29:40Z
• Authors: Antoine Petitcollin; Charlène Brochard; Laurent Siproudhis; Camille Tron; Marie‐Clémence Ve...; Florian Lemaitre; Camille Lucidarme; Guillaume Bouguen; Éric Bellissant
• Keywords: Adult; Male; Time Factors; Metabolic Clearance Rate; Tobacco Use; 03 medical and health sciences; Dose tapering; 0302 clinical medicine; Gastrointestinal Agents; Recurrence; Humans; Proportional Hazards Models; Therapeutic Drug Monitoring; Remission Induction; [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy; Middle Aged; Inflammatory Bowel Diseases; Real-World Data; De-escalation; Infliximab; 3. Good health; Population Pharmacokinetics; C-Reactive Protein; [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology; Colitis, Ulcerative; Female

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.