scholarly journals Infliximab clearance decreases in the second and third trimesters of pregnancy in inflammatory bowel disease

2020 ◽  
pp. 205064062096461
Author(s):  
Ana-Marija Grišić ◽  
Maria Dorn-Rasmussen ◽  
Bella Ungar ◽  
Jørn Brynskov ◽  
Johan F K F Ilvemark ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
First Trimester ◽  
Interquartile Range ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Second Trimester ◽  
Third Trimester ◽  
The Third ◽  
Inflammatory Bowel

Background Infliximab 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. Methods The 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 post-pregnancy ( n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modelling. Results Dose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 µg/mL/kg, interquartile range 10–21) compared to pre-pregnancy (7, 2–12; p = 0.003), the first trimester (9, 1–12; p = 0.04), or post-pregnancy (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 = 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 post-pregnancy 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. Conclusion Infliximab 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.

Safety and Optimal Timing of BCG Vaccination in Infants Born to Mothers Receiving Anti-TNF Therapy for Inflammatory Bowel Disease

2020 ◽  
Vol 14 (12) ◽  
pp. 1780-1784 ◽  
Author(s):  
Sang Hyoung Park ◽  
Hyo Jong Kim ◽  
Chang Kyun Lee ◽  
Eun Mi Song ◽  
Sang-Bum Kang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Adverse Events ◽  
Bowel Disease ◽  
Optimal Timing ◽  
Third Trimester ◽  
Serious Adverse Events ◽  
Bcg Vaccination ◽  
The Third ◽  
Gestational Week ◽  
Inflammatory Bowel

Abstract Backgrounds and Aims We aimed to evaluate the safety of Bacille Calmette–Guérin [BCG] vaccination in infants born to mothers receiving anti-tumour necrosis factor [anti-TNF] therapy for inflammatory bowel disease. Methods Adverse events of BCG vaccination were evaluated in 90 infants who were last exposed to anti-TNF agents at a median of gestational week 30. Results After receiving BCG vaccination at a median age of 6 months [range, 0.25–11 months], three infants [3.3%] showed injection site swelling, two of whom also showed axillar lymphadenopathy. The rates of adverse events were similar between infants who were last exposed to anti-TNF agents before the third trimester [n = 35] and those who were last exposed in the third trimester [n = 55] [2.9% vs 3.6%; p = 1.00]. All adverse events were spontaneously resolved and there were no serious adverse events such as active tuberculosis infection or death. Conclusions BCG vaccination after 6 months of age is of low risk in infants exposed to anti-TNF agents in utero.

scholarly journals Management of the Pregnant Inflammatory Bowel Disease Patient on Antitumour Necrosis Factor Therapy: State of the Art and Future Directions

2014 ◽  
Vol 28 (9) ◽  
pp. 505-509 ◽  
Author(s):  
Yvette PY Leung ◽  
Remo Panaccione ◽  
Subrata Ghosh ◽  
Cynthia H Seow
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Disease Patient ◽  
Mucosal Healing ◽  
Infectious Complications ◽  
Major Advance ◽  
Third Trimester ◽  
The Third ◽  
Inflammatory Bowel ◽  
Necrosis Factor

Antitumour necrosis factor (anti-TNF) therapy has been a major advance in the treatment of inflammatory bowel disease (IBD) by improving rates of mucosal healing, steroid-free remission, and decreasing rates of hospitalization and surgery. Because IBD affects women in their reproductive years, clinicians have and will continue to be asked in the future about the safety profile of these agents and their potential impact on pregnancy, the developing fetus and newborn. Immunoglobulin G transfer from the mother to fetus begins in the second trimester, with an elevation starting at 22 weeks of gestation and the largest amount transferred in the third trimester. Although research investigating the long-term outcomes of children exposed to anti-TNF therapy in utero is limited, there is no known adverse effect on either pregnancy or newborn outcomes including infectious complications with this class of drugs. The World Congress of Gastroenterology consensus statement on biological therapy for IBD considered infliximab and adalimumab to be low risk and compatible with use during conception and during pregnancy in at least the first two trimesters. Based on a clinical algorithm used at the University of Calgary Pregnancy and IBD clinic (Calgary, Alberta), recommendations have been provided on the management of pregnant patients on anti-TNF therapy, particularly with regard to third-trimester dosing, taking into account disease characteristics of individual patients. When educated about the safety of anti-TNF therapy during pregnancy, patients often choose to continue on therapy during the third trimester.

Therapeutic drug monitoring with vedolizumab in inflammatory bowel disease

2020 ◽  
Vol 65 (4) ◽  
Author(s):  
Daniela Pugliese ◽  
Giuseppe Privitera ◽  
Fabrizio Pizzolante ◽  
Antonio Gasbarrini ◽  
Luisa Guidi ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Inflammatory Bowel

scholarly journals A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 162-163
Author(s):  
M Mikail ◽  
A Wilson
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pyoderma Gangrenosum ◽  
Bowel Disease ◽  
Complete Resolution ◽  
Therapeutic Drug ◽  
Drug Concentrations ◽  
Median Serum ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD. Aims To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD. Methods Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment. Results Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment. Conclusions Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD. Funding Agencies NoneNone.

scholarly journals P546 Therapeutic drug monitoring of vedolizumab in inflammatory bowel disease

2019 ◽  
Vol 13 (Supplement_1) ◽  
pp. S387-S387
Author(s):  
N Torres ◽  
D Martín Arranz ◽  
M Sánchez Azofra ◽  
E Martín Arranz ◽  
L Garcia ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Therapeutic Drug Monitoring ◽  
Bowel Disease ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Inflammatory Bowel
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