Dataset Information

Impact of first-line infliximab on the pharmacokinetics of second-line vedolizumab in inflammatory bowel diseases.

ABSTRACT:

Background

Very little is known about the impact of the wash-out period on the pharmacokinetics of a second-line biologic.

Objective

The objective of this article is to explore the impact of two different wash-out periods on the pharmacokinetics of vedolizumab and infliximab.

Methods

Patients switching from infliximab to vedolizumab were retrospectively identified. The population was divided into two groups according to wash-out period: <6 weeks or >6 weeks. Vedolizumab and infliximab trough levels (TLs) were determined and correlated with clinical and biological outcomes.

Results

A total of 71 inflammatory bowel disease patients were included. At week 6, in patients previously treated with infliximab, median vedolizumab TLs were 21.9 µg/ml and 24.9 µg/ml for the <6 weeks and >6 weeks wash-out period, respectively (p = 0.31), whereas median residual infliximab TLs were 0.5 µg/ml and 0 µg/ml (p = 0.034). The rate of treatment discontinuation was similar (p = 0.64), and the infectious events were six and two for the <6 weeks and >6 weeks wash-out period, respectively (p = 0.12) by week 30.

Conclusions

This study suggests clinicians may not need to be concerned about the impact of wash-out period on the pharmacokinetics of the second-line biologic when switching infliximab to vedolizumab. More data are required on the impact of wash-out period on safety.

SUBMITTER: Liefferinckx C

PROVIDER: S-EPMC6620879 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Impact of first-line infliximab on the pharmacokinetics of second-line vedolizumab in inflammatory bowel diseases.

Liefferinckx Claire C Verstockt Bram B Gils Ann A Tops Sophie S Van Moerkercke Wouter W Vermeire Severine S Franchimont Denis D

United European gastroenterology journal 20190324 6

<h4>Background</h4>Very little is known about the impact of the wash-out period on the pharmacokinetics of a second-line biologic.<h4>Objective</h4>The objective of this article is to explore the impact of two different wash-out periods on the pharmacokinetics of vedolizumab and infliximab.<h4>Methods</h4>Patients switching from infliximab to vedolizumab were retrospectively identified. The population was divided into two groups according to wash-out period: <6 weeks or >6 weeks. Vedolizumab and ...[more]

PMID: 31316779

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Project description:BackgroundInfliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal infliximab exposure. We investigated the effects of pregnancy on infliximab pharmacokinetics.MethodsThe study population comprised 23 retrospectively identified pregnancies. Patients with inflammatory bowel disease were generally in clinical remission at pregnancy conception (74%) and received steady infliximab maintenance therapy (5 mg/kg q8w n = 17; q6w n = 4; q10w n = 1; 10 mg/kg q8w n = 1). Trough blood samples had been obtained in the same patients prior to pregnancy (n = 119), the first trimester (n = 16), second trimester (n = 18), third trimester (n = 7), and postpregnancy (n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modeling.ResultsDose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 mg/ml/kg, interquartile range 10-21) compared to prepregnancy (7, 2-12; p = 0.003), the first trimester (9, 1-12; p = 0.04), or postpregnancy (6, interquartile range 3-11; p > 0.05) in patients with inflammatory bowel disease. Similar trends were observed in the third trimester (13, 7-36; p > 0.05). A one-compartment model with linear elimination described the pharmacokinetics of infliximab (volume of distribution n = 18.2 L; clearance 0.61 L/day). Maternal infliximab exposure was influenced by the second and third trimester of pregnancy and anti-infliximab antibodies, and not by pregnancy-imposed physiological changes in, for example, body weight or albumin. Infliximab clearance decreased significantly during the second and third trimesters by up to 15% as compared to pre- and postpregnancy and the first trimester. The increased maternal infliximab exposure was weakly associated with lowered clinical disease activity. Pharmacokinetic model simulations of virtual patients indicated the increased maternal infliximab trough concentrations imposed by pregnancy will not completely counteract the decrease in infliximab concentration if therapy is paused in the third trimester.ConclusionInfliximab clearance decreases significantly in the second and third trimesters, leading to increasing maternal infliximab concentrations in any given regimen. Maternal infliximab levels may thus be maintained as constant in a de-intensified regimen by therapeutic drug monitoring guidance in inflammatory bowel disease.

Dataset Information

Impact of first-line infliximab on the pharmacokinetics of second-line vedolizumab in inflammatory bowel diseases.

Background

Objective

Methods

Results

Conclusions

Publications

Impact of first-line infliximab on the pharmacokinetics of second-line vedolizumab in inflammatory bowel diseases.

Similar Datasets

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