TY - JOUR
T1 - Application of a Precision-Dosing Model to a Real-World Cohort of Patients on Infliximab Maintenance Therapy
T2 - Drug Usage and Cost Analysis
AU - Nguyen, Anke L.
AU - Gibson, Peter R.
AU - Upton, Richard N.
AU - Mould, Diane R.
AU - Sparrow, Miles P.
N1 - Funding Information:
A.L.N. was supported by the Research Training Program stipend (Monash University).
Funding Information:
A.L.N. and P.R.G. have no financial disclosures. R.N.U. and D.R.M. are both employed by Projections Research Inc., a consulting company for the pharmaceutical industry. R.N.U. has contributed code to the iDOSE software. D.R.M. holds multiple patents on individualized dosing and the iDOSE technology; has been an expert witness on behalf of AbbVie and Eli Lilly; has participated in Data Safety Monitoring for multiple clients; and holds shares of Pfizer and Amgen. M.P.S. has received educational grants or research support from Ferring, Orphan, Gilead, and Celltrion ; has received speakers fees from Janssen, Abbvie, Ferring, Takeda, Pfizer, Shire, Celltrion, and Eli Lilly; and has served on advisory boards for Janssen, Takeda, Pfizer, Celgene, Abbvie, MSD, Emerge Health, Gilead, BMS, Celltrion, and Eli Lilly.
Publisher Copyright:
© 2023 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.
PY - 2024/4
Y1 - 2024/4
N2 - Precision-dosing models forecast infliximab doses to achieve targeted trough concentrations in patients with inflammatory bowel disease (IBD). These models have shown to reduce nonresponse and improve patient outcomes. We compared infliximab doses determined by iDOSE precision dosing with standard dosing, and the associated drug costs, in patients with IBD. In this retrospective study, patients with IBD treated with infliximab every 8 weeks at 5 mg/kg were included. An infliximab dose was named dose X if 3 previous infliximab doses, laboratory values including trough infliximab concentrations, and the patient's weight were recorded. The actual dose X was compared to an iDOSE-predicted dose X. Net drug use and costs were evaluated. A total of 174 patients—56% men; median age, 36 (interquartile range, 29-47) years; 135 with Crohn disease; and 31 with ulcerative colitis—were included, with 417 dose X recordings. Median prior infliximab therapy was 2 (0-4) years. Comparing actual dose X with predicted dose X, 52% and 32% of doses were subtherapeutic when aiming for trough concentrations of 5-10 and 3-7 μg/mL, respectively. Treatment costs increased by 102% and 29% for the 2 trough ranges, respectively. On multivariate regression analysis, subtherapeutic infliximab concentrations were associated with ulcerative colitis compared with Crohn disease (odds ratio, 9.81; 95% confidence interval, 1.28-75.40; P =.028) and predose X infliximab trough concentration [odds ratio, 0.07; 95% confidence interval, 0.03-0.15; P <.001]. Over half of maintenance infliximab drug doses were too low to achieve infliximab blood concentrations of 5 μg/mL or greater. While applying precision dosing may improve patient outcomes, drug costs could be considerably greater.
AB - Precision-dosing models forecast infliximab doses to achieve targeted trough concentrations in patients with inflammatory bowel disease (IBD). These models have shown to reduce nonresponse and improve patient outcomes. We compared infliximab doses determined by iDOSE precision dosing with standard dosing, and the associated drug costs, in patients with IBD. In this retrospective study, patients with IBD treated with infliximab every 8 weeks at 5 mg/kg were included. An infliximab dose was named dose X if 3 previous infliximab doses, laboratory values including trough infliximab concentrations, and the patient's weight were recorded. The actual dose X was compared to an iDOSE-predicted dose X. Net drug use and costs were evaluated. A total of 174 patients—56% men; median age, 36 (interquartile range, 29-47) years; 135 with Crohn disease; and 31 with ulcerative colitis—were included, with 417 dose X recordings. Median prior infliximab therapy was 2 (0-4) years. Comparing actual dose X with predicted dose X, 52% and 32% of doses were subtherapeutic when aiming for trough concentrations of 5-10 and 3-7 μg/mL, respectively. Treatment costs increased by 102% and 29% for the 2 trough ranges, respectively. On multivariate regression analysis, subtherapeutic infliximab concentrations were associated with ulcerative colitis compared with Crohn disease (odds ratio, 9.81; 95% confidence interval, 1.28-75.40; P =.028) and predose X infliximab trough concentration [odds ratio, 0.07; 95% confidence interval, 0.03-0.15; P <.001]. Over half of maintenance infliximab drug doses were too low to achieve infliximab blood concentrations of 5 μg/mL or greater. While applying precision dosing may improve patient outcomes, drug costs could be considerably greater.
KW - biologics
KW - biomarkers
KW - clinical pharmacology
KW - gastrointestinal
KW - pharmacokinetics and drug metabolism
UR - http://www.scopus.com/inward/record.url?scp=85178475803&partnerID=8YFLogxK
U2 - 10.1002/jcph.2384
DO - 10.1002/jcph.2384
M3 - Article
C2 - 37964618
AN - SCOPUS:85178475803
SN - 0091-2700
VL - 64
SP - 399
EP - 409
JO - The Journal of Clinical Pharmacology
JF - The Journal of Clinical Pharmacology
IS - 4
ER -