TY - JOUR
T1 - Therapeutic drug monitoring of methotrexate in patients with Crohn's disease
AU - van de Meeberg, Maartje M
AU - Fidder, Herma H
AU - Oldenburg, Bas
AU - Sundaresan, Janani
AU - Struys, Eduard A
AU - Montazeri, Nahid S M
AU - Mares, Wout G N
AU - Mahmmod, Nofel
AU - van Asseldonk, Dirk P
AU - Lutgens, Maurice W M D
AU - Kuyvenhoven, Johan P
AU - Rietdijk, Svend T
AU - Nissen, Loes H C
AU - Koehestanie, Parweez
AU - de Boer, Nanne K H
AU - de Jonge, Robert
AU - Bouma, Gerd
AU - Bulatović Ćalasan, Maja
N1 - Publisher Copyright:
© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PY - 2023/12
Y1 - 2023/12
N2 - BACKGROUND: Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate-polyglutamate (MTX-PG) in erythrocytes might enable TDM for methotrexate in patients with Crohn's disease (CD).AIM: To investigate the relationship between MTX-PGs and methotrexate drug survival, efficacy and toxicity METHODS: In a multicentre prospective cohort study, patients with CD starting subcutaneous methotrexate without biologics were included and followed for 12 months. Primary outcome was subcutaneous methotrexate discontinuation or requirement for step-up therapy. Secondary outcomes included faecal calprotectin (FCP), Harvey Bradshaw Index (HBI), hepatotoxicity and gastrointestinal intolerance. Erythrocyte MTX-PGs were analysed at weeks 8, 12, 24 and 52 or upon treatment discontinuation.RESULTS: We included 80 patients with CD (mean age 55 ± 13y, 35% male) with a median FCP of 268 μg/g (IQR 73-480). After the 12-month visit, 21 patients (26%) were still on subcutaneous methotrexate monotherapy. Twenty-one patients stopped because of disease activity, 29 because of toxicity, and four for both reasons. Five patients ended study participation or stopped methotrexate for another reason. A higher MTX-PG
3 concentration was associated with a higher rate of methotrexate drug survival (HR 0.86, 95% CI 0.75-0.99), lower FCP (β -3.7, SE 1.3, p < 0.01) and with biochemical response (FCP ≤250 if baseline >250 μg/g; OR 1.1, 95% CI 1.0-1.3). Higher MTX-PGs were associated with less gastrointestinal intolerance. There was no robust association between MTX-PGs and HBI or hepatotoxicity.
CONCLUSIONS: Higher MTX-PG
3 concentrations are related to better methotrexate drug survival and decreased FCP levels. Therefore, MTX-PG
3 could be used for TDM if a target concentration can be established.
AB - BACKGROUND: Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate-polyglutamate (MTX-PG) in erythrocytes might enable TDM for methotrexate in patients with Crohn's disease (CD).AIM: To investigate the relationship between MTX-PGs and methotrexate drug survival, efficacy and toxicity METHODS: In a multicentre prospective cohort study, patients with CD starting subcutaneous methotrexate without biologics were included and followed for 12 months. Primary outcome was subcutaneous methotrexate discontinuation or requirement for step-up therapy. Secondary outcomes included faecal calprotectin (FCP), Harvey Bradshaw Index (HBI), hepatotoxicity and gastrointestinal intolerance. Erythrocyte MTX-PGs were analysed at weeks 8, 12, 24 and 52 or upon treatment discontinuation.RESULTS: We included 80 patients with CD (mean age 55 ± 13y, 35% male) with a median FCP of 268 μg/g (IQR 73-480). After the 12-month visit, 21 patients (26%) were still on subcutaneous methotrexate monotherapy. Twenty-one patients stopped because of disease activity, 29 because of toxicity, and four for both reasons. Five patients ended study participation or stopped methotrexate for another reason. A higher MTX-PG
3 concentration was associated with a higher rate of methotrexate drug survival (HR 0.86, 95% CI 0.75-0.99), lower FCP (β -3.7, SE 1.3, p < 0.01) and with biochemical response (FCP ≤250 if baseline >250 μg/g; OR 1.1, 95% CI 1.0-1.3). Higher MTX-PGs were associated with less gastrointestinal intolerance. There was no robust association between MTX-PGs and HBI or hepatotoxicity.
CONCLUSIONS: Higher MTX-PG
3 concentrations are related to better methotrexate drug survival and decreased FCP levels. Therefore, MTX-PG
3 could be used for TDM if a target concentration can be established.
UR - http://www.scopus.com/inward/record.url?scp=85173082955&partnerID=8YFLogxK
U2 - 10.1111/apt.17719
DO - 10.1111/apt.17719
M3 - Article
C2 - 37767910
SN - 0269-2813
VL - 58
SP - 1151
EP - 1162
JO - Alimentary Pharmacology & Therapeutics
JF - Alimentary Pharmacology & Therapeutics
IS - 11-12
ER -