The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in inflammatory bowel disease.
BACKGROUND
Transplacental transfer of infliximab and adalimumab results in detectable drug levels in the cord blood and infant.


OBJECTIVE
To determine if pregnancy influenced the pharmacokinetics of anti-TNF agents in women with inflammatory bowel disease.


METHODS
Twenty-five women from the University of Calgary inflammatory bowel disease(IBD) pregnancy clinic on maintenance infliximab or adalimumab were recruited prospectively with serum bio-banking performed each trimester. Infliximab trough and adalimumab steady-state levels were the outcomes of interest and were analysed using the ANSER infliximab and adalimumab assays. Multivariate linear mixed-effects models were constructed to assess infliximab and adalimumab drug levels during pregnancy adjusting for the clinical covariates of albumin, BMI and CRP.


RESULTS
Fifteen women (eight Crohn's disease, seven ulcerative colitis) received infliximab and 10 women with 11 pregnancies were treated with adalimumab. Median age was 29.6 years (IQR: 27.6-31.2 years). Median disease duration was 9.2 years (IQR: 3.16-15.0 years). Median trough infliximab concentrations were 8.50 μg/mL (IQR: 7.23-10.07 μg/mL), 10.31 μg/mL (IQR: 7.66-15.63 μg/mL) and 21.02 μg/mL (IQR: 16.01-26.70 μg/mL) at trimesters 1, 2 and 3 respectively. Significant changes in albumin and BMI (P < 0.05) but not CRP (P > 0.05) were documented throughout pregnancy. After adjusting for albumin, BMI and CRP, infliximab trough levels increased during pregnancy, by 4.2 μg/mL per trimester (P = 0.02), while adalimumab drug levels remained stable (P > 0.05).


CONCLUSIONS
Infliximab levels rise during pregnancy, whereas adalimumab levels remain stable after accounting for changes in albumin, BMI and CRP. Therapeutic drug monitoring in the second trimester may be useful in guiding dosing in the third trimester.
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.|Department of Community Health Sciences, University of Calgary, Calgary, Canada.
C H
http://orcid.org/0000-0002-1551-9054
CH
Seow
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
Y
Y
Leung
Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
N
N
Vande Casteele
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
E
E
Ehteshami Afshar
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
D
D
Tanyingoh
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
G
G
Bindra
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
M J
MJ
Stewart
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
P L
PL
Beck
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.|Department of Community Health Sciences, University of Calgary, Calgary, Canada.
G G
http://orcid.org/0000-0003-2719-0556
GG
Kaplan
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
S
S
Ghosh
Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, Canada.
R
R
Panaccione
D000068879:Adalimumab / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism*; D000069285:Infliximab / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D021041:Placental Circulation; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab