Premedication with corticosteroids does not impact the pharmacokinetics of infliximab in inflammatory bowel disease irrespective of azathioprine cotreatment

Lone Larsen, Tine Jess, Asbjørn M Drewes, Anders Dige, Jan Fallingborg, Bent A Jacobsen, Bitten Aagaard, Jørgen Agnholt

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

1 Citation (Scopus)

Resumé

ObjectiveLoss of infliximab (IFX) effect is a clinical challenge in the management of patients with Crohn's disease (CD), but this can potentially be reduced with azathioprine (AZA) or with corticosteroids (CS). We aimed to study whether CS premedication with or without cotreatment with AZA could reduce antibody formation and affect the IFX elimination rate.Patients and methodsA cross-sectional observational study was conducted at two centers with CD patients receiving maintenance IFX therapy for 12-18 months. In addition to IFX, patients received either CS premedication or not, with or without concominant AZA.ResultsFifty-seven patients were included in the study. Thirty-one patients received premedication with CSs, and 11 (35.5%) of these also received AZA, whereas this was the case for 22 of 26 (84.6%) patients in the non-CS group. No difference in IFX trough level (P=0.10) or halftime elimination (P=0.31) was observed with or without CS premedication. Concomitant AZA was associated with significantly longer mean half-life of IFX (P=0.04). Total IFX antibody concentrations were 15.8 and 12.9 with and without CS, respectively, in those not receiving AZA versus 4.3 and 6.1 AU/ml with and without CS, respectively, in those receiving AZA (P=0.004). Premedication with CS did not have any effect on the frequency of antibody formation (P=0.28).ConclusionIn patients with CD and in maintenance IFX therapy, premedication with CS did not influence antibody formation, IFX trough levels or IFX halftime elimination, irrespective of concomitant AZA use. However, the use of AZA was associated with higher IFX trough levels and lower total IFX antibody concentrations.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Gastroenterology and Hepatology
Vol/bind31
Udgave nummer8
Sider (fra-til)964-967
Antal sider4
ISSN0954-691X
DOI
StatusUdgivet - aug. 2019

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Premedication
Azathioprine
Inflammatory Bowel Diseases
Adrenal Cortex Hormones
Pharmacokinetics
Crohn Disease
Antibody Formation
Infliximab
Maintenance
Antibodies
Observational Studies
Half-Life
Cross-Sectional Studies

Citer dette

@article{13fe95ccf7004203a48022f558827000,
title = "Premedication with corticosteroids does not impact the pharmacokinetics of infliximab in inflammatory bowel disease irrespective of azathioprine cotreatment",
abstract = "ObjectiveLoss of infliximab (IFX) effect is a clinical challenge in the management of patients with Crohn's disease (CD), but this can potentially be reduced with azathioprine (AZA) or with corticosteroids (CS). We aimed to study whether CS premedication with or without cotreatment with AZA could reduce antibody formation and affect the IFX elimination rate.Patients and methodsA cross-sectional observational study was conducted at two centers with CD patients receiving maintenance IFX therapy for 12-18 months. In addition to IFX, patients received either CS premedication or not, with or without concominant AZA.ResultsFifty-seven patients were included in the study. Thirty-one patients received premedication with CSs, and 11 (35.5{\%}) of these also received AZA, whereas this was the case for 22 of 26 (84.6{\%}) patients in the non-CS group. No difference in IFX trough level (P=0.10) or halftime elimination (P=0.31) was observed with or without CS premedication. Concomitant AZA was associated with significantly longer mean half-life of IFX (P=0.04). Total IFX antibody concentrations were 15.8 and 12.9 with and without CS, respectively, in those not receiving AZA versus 4.3 and 6.1 AU/ml with and without CS, respectively, in those receiving AZA (P=0.004). Premedication with CS did not have any effect on the frequency of antibody formation (P=0.28).ConclusionIn patients with CD and in maintenance IFX therapy, premedication with CS did not influence antibody formation, IFX trough levels or IFX halftime elimination, irrespective of concomitant AZA use. However, the use of AZA was associated with higher IFX trough levels and lower total IFX antibody concentrations.",
keywords = "Antibodies, Crohn's disease, infliximab, premedication",
author = "Lone Larsen and Tine Jess and Drewes, {Asbj{\o}rn M} and Anders Dige and Jan Fallingborg and Jacobsen, {Bent A} and Bitten Aagaard and J{\o}rgen Agnholt",
year = "2019",
month = "8",
doi = "10.1097/MEG.0000000000001440",
language = "English",
volume = "31",
pages = "964--967",
journal = "European Journal of Gastroenterology and Hepatology",
issn = "0954-691X",
publisher = "Lippincott Williams & Wilkins, Ltd.",
number = "8",

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TY - JOUR

T1 - Premedication with corticosteroids does not impact the pharmacokinetics of infliximab in inflammatory bowel disease irrespective of azathioprine cotreatment

AU - Larsen, Lone

AU - Jess, Tine

AU - Drewes, Asbjørn M

AU - Dige, Anders

AU - Fallingborg, Jan

AU - Jacobsen, Bent A

AU - Aagaard, Bitten

AU - Agnholt, Jørgen

PY - 2019/8

Y1 - 2019/8

N2 - ObjectiveLoss of infliximab (IFX) effect is a clinical challenge in the management of patients with Crohn's disease (CD), but this can potentially be reduced with azathioprine (AZA) or with corticosteroids (CS). We aimed to study whether CS premedication with or without cotreatment with AZA could reduce antibody formation and affect the IFX elimination rate.Patients and methodsA cross-sectional observational study was conducted at two centers with CD patients receiving maintenance IFX therapy for 12-18 months. In addition to IFX, patients received either CS premedication or not, with or without concominant AZA.ResultsFifty-seven patients were included in the study. Thirty-one patients received premedication with CSs, and 11 (35.5%) of these also received AZA, whereas this was the case for 22 of 26 (84.6%) patients in the non-CS group. No difference in IFX trough level (P=0.10) or halftime elimination (P=0.31) was observed with or without CS premedication. Concomitant AZA was associated with significantly longer mean half-life of IFX (P=0.04). Total IFX antibody concentrations were 15.8 and 12.9 with and without CS, respectively, in those not receiving AZA versus 4.3 and 6.1 AU/ml with and without CS, respectively, in those receiving AZA (P=0.004). Premedication with CS did not have any effect on the frequency of antibody formation (P=0.28).ConclusionIn patients with CD and in maintenance IFX therapy, premedication with CS did not influence antibody formation, IFX trough levels or IFX halftime elimination, irrespective of concomitant AZA use. However, the use of AZA was associated with higher IFX trough levels and lower total IFX antibody concentrations.

AB - ObjectiveLoss of infliximab (IFX) effect is a clinical challenge in the management of patients with Crohn's disease (CD), but this can potentially be reduced with azathioprine (AZA) or with corticosteroids (CS). We aimed to study whether CS premedication with or without cotreatment with AZA could reduce antibody formation and affect the IFX elimination rate.Patients and methodsA cross-sectional observational study was conducted at two centers with CD patients receiving maintenance IFX therapy for 12-18 months. In addition to IFX, patients received either CS premedication or not, with or without concominant AZA.ResultsFifty-seven patients were included in the study. Thirty-one patients received premedication with CSs, and 11 (35.5%) of these also received AZA, whereas this was the case for 22 of 26 (84.6%) patients in the non-CS group. No difference in IFX trough level (P=0.10) or halftime elimination (P=0.31) was observed with or without CS premedication. Concomitant AZA was associated with significantly longer mean half-life of IFX (P=0.04). Total IFX antibody concentrations were 15.8 and 12.9 with and without CS, respectively, in those not receiving AZA versus 4.3 and 6.1 AU/ml with and without CS, respectively, in those receiving AZA (P=0.004). Premedication with CS did not have any effect on the frequency of antibody formation (P=0.28).ConclusionIn patients with CD and in maintenance IFX therapy, premedication with CS did not influence antibody formation, IFX trough levels or IFX halftime elimination, irrespective of concomitant AZA use. However, the use of AZA was associated with higher IFX trough levels and lower total IFX antibody concentrations.

KW - Antibodies

KW - Crohn's disease

KW - infliximab

KW - premedication

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U2 - 10.1097/MEG.0000000000001440

DO - 10.1097/MEG.0000000000001440

M3 - Journal article

VL - 31

SP - 964

EP - 967

JO - European Journal of Gastroenterology and Hepatology

JF - European Journal of Gastroenterology and Hepatology

SN - 0954-691X

IS - 8

ER -