title: Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.
abstract: Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.
authors.affiliation: Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Marla.dubinsky@mssm.edu.
authors.forename: Marla C
authors.initials: MC
authors.lastname: Dubinsky
authors.affiliation: Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Becky L
authors.initials: BL
authors.lastname: Phan
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Namita
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Pediatrics, Division of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Shervin
authors.initials: S
authors.lastname: Rabizadeh
authors.affiliation: Projections Research Inc., Phoenixville, Pennsylvania, USA.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Mould
mesh_terms: D000906:Antibodies / Q000097:blood; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000178:diet therapy*; D000069285:Infliximab / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D017410:Practice Guidelines as Topic / Q000592:standards*; D059039:Standard of Care; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000906:Antibodies; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: anti-drug antibodies; dashboards; decision support tools; inflammatory bowel disease; infliximab; personalized medicine; therapeutic monitoring; trough concentrations