Pregnancy increases IFX trough levels but not ADA

May 8, 2018 - E-Mentoring in IBD | Volume 11 • 2018

Issue 09

Clinical Question

Does pregnancy change the pharmacokinetics of either infliximab (IFX) or adalimumab (ADA) and influence the value of serum drug monitoring?

Editor’s Bottom Line

IFX levels may rise during pregnancy. The role of therapeutic drug monitoring and/or dose adjustments in late pregnancy need further study.

Reference

Seow CH, Leung Y, Vande Casteele N, et al. The effects of pregnancy on the pharmacokinetics of infliximab and adalimumab in inflammatory bowel disease. Aliment Pharmacol Ther. 2017 May;45(10):1329–38. http://www.ncbi.nlm.nih.gov/pubmed/28318043

Synopsis

Women from the University of Calgary IBD pregnancy clinic receiving maintenance IFX or ADA were recruited into the study if they became pregnant between 2012 and 2014. Disease activity, medication use, anti-TNF treatment dates, concomitant thiopurine use, and pregnancy outcomes were recorded at each visit. Serum was collected either 1 week prior to IFX infusion or at ADA steady state. Up to 6 samples were collected per patient. Thresholds for the presence of anti-TNF in the sera were: IFX >1.0 µg/ml and ADA >1.6 µg/ml; thresholds for the detection of antibodies were: IFX >3.1 U/ml and ADA >1.7 U/ml. The primary outcomes were the changes in anti-TNF levels, albumin, BMI, and CRP during pregnancy.

The IFX cohort was comprised of 8 and 7 women with CD and UC, respectively, who had 15 pregnancies. The median IFX dose was 5.29 mg/kg at a median of 7 weeks. Median trough IFX concentrations at trimesters 1, 2, and 3 were 8.5 µg/ml (IQR: 7.2–10.1), 10.3 µg/ml (7.7–15.7), and 21.0 µg/ml (16.0–26.7), respectively. The ADA cohort included 9 women with CD and 1 with UC for a combined total of 11 pregnancies. The ADA dose administered was 40 mg either biweekly (n=9) or weekly (n=2). ADA antibodies were detected in 2 women. No correlations were found between anti-TNF drug level and time since last treatment. During pregnancy, albumin levels and BMI changed significantly, but not CRP. IFX trough levels progressively increased across pregnancy even after adjusting for albumin, BMI, and CRP. Conversely, ADA levels remained stable throughout.

Details

Study Design: Prospective longitudinal study
Funding: None
Allocation: n/a
Setting: Calgary, AB
Level of Evidence: 2b (Oxford Levels of Evidence)

The summary and conclusion in this issue of E-mentoring in IBD pertains to the manuscript(s) being reviewed, and should be considered in the context of what is already known surrounding the topic and incorporated into practice as deemed appropriate by the individual learner.