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.
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Author Contributions
1. Conception and design of the study: MCD and DRM
2. Generation, collection, assembly, analysis, and interpretation of data: MCD, DRM, and BLP
3. Drafting or revision of the manuscript MCD, DRM, and BLP
4. Approval of the final version of the manuscript: MCD, DRM, BLP, SR, and NS
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The study was approved by CSMC Institutional Review Board (IRB no. 19251); all patients signed informed consent before enrollment.
Disclosures
Marla C. Dubinsky: Consultant for Prometheus Labs, Janssen, AbbVie
Becky L. Phan: Nothing to disclose
Namita Singh: Janssen—research grant
Shervin Rabizadeh: Consultant for Prometheus Labs
Diane R. Mould: President of Projections Research Inc. a consulting company for the Pharmaceutical Industry
Grant Support
Partially funded by the NIH/NIDDK (1R21DK084554-01) (MCD), Claire and Abe Levine Chair in Pediatric IBD Research (MCD).
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Dubinsky, M.C., Phan, B.L., Singh, N. et al. Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients. AAPS J 19, 215–222 (2017). https://doi.org/10.1208/s12248-016-9994-y
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DOI: https://doi.org/10.1208/s12248-016-9994-y