Optimising infliximab induction dosing for patients with ulcerative colitis

The therapeutic failure of infliximab therapy in patients with ulcerative colitis remains a challenge even 2 decades after its approval. Therapeutic drug monitoring (TDM) has shown value during maintenance therapy, but induction therapy has still not been explored. Patients may be primary nonresponders or underexposed with the standard dosing regimen. We aimed to: (i) develop a population pharmacokinetic‐pharmacodynamic model; (ii) identify the best exposure metric that predicts mucosal healing; and (iii) build an exposure–response (ER) model to demonstrate model‐based dose finding during induction therapy with infliximab.

[1]  R. Irizarry.  ggplot2 , 2019, Introduction to Data Science.

[2]  D. Franchimont,et al.  Increasing Infliximab Dose Based on Symptoms, Biomarkers, and Serum Drug Concentrations Does Not Increase Clinical, Endoscopic, and Corticosteroid-Free Remission in Patients With Active Luminal Crohn's Disease. , 2018, Gastroenterology.

[3]  S. Suryawanshi,et al.  Reporting, Visualization, and Modeling of Immunogenicity Data to Assess Its Impact on Pharmacokinetics, Efficacy, and Safety of Monoclonal Antibodies , 2018, The AAPS Journal.

[4]  Alasdair J. G. Gray,et al.  The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY , 2017, Nucleic Acids Res..

[5]  Christopher Southan,et al.  THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Catalytic receptors , 2017, British journal of pharmacology.

[6]  A. Gils,et al.  Practical recommendations for the use of therapeutic drug monitoring of biopharmaceuticals in inflammatory diseases , 2017, Clinical pharmacology : advances and applications.

[7]  S. Vermeire,et al.  Rapid Test for Infliximab Drug Concentration Allows Immediate Dose Adaptation , 2016, Clinical and translational gastroenterology.

[8]  K. Farkas,et al.  Efficacy of Infliximab Biosimilar CT-P13 Induction Therapy on Mucosal Healing in Ulcerative Colitis. , 2016, Journal of Crohn's & colitis.

[9]  P. Goupille,et al.  The underlying inflammatory chronic disease influences infliximab pharmacokinetics , 2016, mAbs.

[10]  M. Karlsson,et al.  Approaches for modeling within subject variability in pharmacometric count data analysis: dynamic inter-occasion variability and stochastic differential equations , 2016, Journal of Pharmacokinetics and Pharmacodynamics.

[11]  D. Mould,et al.  Clinical Decision Support Tools: The Evolution of a Revolution , 2016, Clinical pharmacology and therapeutics.

[12]  P. Rutgeerts,et al.  Infliximab Concentration Thresholds During Induction Therapy Are Associated With Short-term Mucosal Healing in Patients With Ulcerative Colitis. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[13]  S. Vermeire,et al.  Pharmacokinetic Modeling and Simulation of Biologicals in Inflammatory Bowel Disease: The Dawning of a New Era for Personalized Treatment. , 2016, Current drug targets.

[14]  C. Ponsioen,et al.  Pharmacokinetic Features and Presence of Antidrug Antibodies Associate With Response to Infliximab Induction Therapy in Patients With Moderate to Severe Ulcerative Colitis. , 2016, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[15]  S. Vermeire,et al.  An Optimized Anti-infliximab Bridging Enzyme-linked Immunosorbent Assay for Harmonization of Anti-infliximab Antibody Titers in Patients with Inflammatory Bowel Diseases , 2015, Inflammatory bowel diseases.

[16]  K. Van Steen,et al.  Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. , 2015, Gastroenterology.

[17]  E. Louis,et al.  Assessment of the Influence of Inflammation and FCGR3A Genotype on Infliximab Pharmacokinetics and Time to Relapse in Patients with Crohn’s Disease , 2015, Clinical Pharmacokinetics.

[18]  P. Rutgeerts,et al.  A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis. , 2015, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[19]  P. Rutgeerts,et al.  Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. , 2014, Gastroenterology.

[20]  L. A. Christensen,et al.  Individualised therapy is more cost-effective than dose intensification in patients with Crohn’s disease who lose response to anti-TNF treatment: a randomised, controlled trial , 2013, Gut.

[21]  S. Vermeire,et al.  Detection of infliximab levels and anti‐infliximab antibodies: a comparison of three different assays , 2012, Alimentary pharmacology & therapeutics.

[22]  Honghui Zhou,et al.  Pharmacokinetic properties of infliximab in children and adults with Crohn's disease: a retrospective analysis of data from 2 phase III clinical trials. , 2011, Clinical therapeutics.

[23]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .

[24]  Honghui Zhou,et al.  PHARMACOKINETICS AND DISPOSITION Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis , 2009 .

[25]  M. Silverberg,et al.  Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis , 2009, Gut.

[26]  T. Grimsrud,et al.  Stability of selected serum proteins after long-term storage in the Janus Serum Bank , 2009, Clinical chemistry and laboratory medicine.

[27]  P. Goupille,et al.  An Enzyme-Linked Immunosorbent Assay for Therapeutic Drug Monitoring of Infliximab , 2006, Therapeutic drug monitoring.

[28]  Paul Rutgeerts,et al.  Infliximab for induction and maintenance therapy for ulcerative colitis. , 2005, The New England journal of medicine.

[29]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[30]  Stephen B. Duffull,et al.  Quantification of Lean Bodyweight , 2005, Clinical pharmacokinetics.