Intrapatient Variability in the Pharmacokinetics of Etanercept Maintenance Treatment.

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ID: 72775
2017
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Abstract
Etanercept has shown to mediate a favorable effect on immune-mediated inflammatory diseases (IMID), including plaque psoriasis. Therapeutic drug monitoring (TDM) of etanercept could improve clinical outcome and cost-effectiveness. A high intrapatient variability (IPV) of etanercept trough concentrations at standard dosing would reduce the feasibility of therapeutic drug monitoring. Studies have focused on the interpatient differences associated with the exposure to biologics. The aim of this study was to determine IPV of etanercept and correlate etanercept trough concentrations and IPV with treatment response.Repetitive serum samples of 29 psoriasis patients on standard etanercept maintenance treatment were collected. In these samples, etanercept trough concentrations were determined and IPV was assessed in relation to response to treatment.The median IPV of etanercept trough concentrations was 33.7% (Q1 = 21.3% and Q3 = 51.7%) ranging from 8% to 155%. All 6 nonresponders showed an IPV at or above the median value of 33.7%. The 6 nonresponders showed a higher IPV as compared to the 23 responders (53.9% versus 24.2%; P = 0.031). The mean etanercept trough concentration for each patient ranged from 0.7 to 6.8 mcg/mL, with a median trough concentration of 2.7 mcg/mL. Patients with an IPV above the median had lower mean etanercept trough concentrations compared to patients with an IPV below the median (1.96 mcg/mL, 95% CI, 1.7-2.4 versus 3.2 mcg/mL, 95% CI, 2.7-4.0; P = 0.001).The median IPV of etanercept trough concentrations in this study population was 33.7%. A higher IPV was correlated with lower etanercept trough concentrations and with nonresponsiveness. Prospective trials are required to demonstrate the value of adjusting the etanercept dose based on drug trough concentrations. The relatively high IPV observed in this study may complicate therapeutic drug monitoring.
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van-bezooijen2017intrapatienttherapeutic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors van Bezooijen, Ji S;Schreurs, Marco W J;Koch, Birgit C P;Velthuis, Henk Te;van Doorn, Martijn B A;Prens, Errol P;van Gelder, Teun;
Journal Therapeutic drug monitoring
Year 2017
DOI
10.1097/FTD.0000000000000384
URL
Keywords
therapeutic drug monitoring sirolimus immunoassay eclia

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