Are IDB Medications Safe for Pregnant Women?

October 14, 2020

The study observed 50 women taking infliximab, adalimumab, and vedolizumab.

Dosing adjustments for patients who are pregnant or planning to become pregnant who have inflammatory bowel disease are likely not necessary, according to a paper published early in Alimentary Pharmacology & Therapeutics.

Investigators from Australia observed 50 pregnant patients with IBD in order to understand the impact of pregnancy on biologic drugs such as infliximab, adalimumab, and vedolizumab levels, as well as the infant’s vedolizumab clearance. There were 23 pregnant (or planning to become pregnant) patients on infliximab, 15 on adalimumab, and 12 on vedolizumab involved in the study between August 2017 and October 2019, the study authors wrote. The women were observed at least twice, from the first trimester to delivery. There were a further 5 patients on vedolizumab the study authors said, but only the mother and baby’s samples were available at delivery.

The study authors wrote that it is known that the pharmacodynamics and pharmacokinetics of many drugs are altered during pregnancy, but said there is nothing in the current literature to suggest that pregnant women should reduce their use of infliximab, adalimumab, and vedolizumab.

Most of the infliximab patients were administered 6-8 weekly at a dose of 6 mg/kg, the study authors said, though one was administered 4-weekly dosing and another received 10 mg/kg. None of the infliximab patients showed significant differences between trimesters 1 and 3 in terms of BMI, C-reactive protein (CRP) and fecal calprotein levels, the study authors said. The median albumin levels decreased from 36.0 g/L in trimester 1 to 30.6 g/L in trimester 2 down to 28.0 g/L in trimester 3, the study authors said.

For the adalimumab group, the study authors said 13 patients were on fortnightly doses and 2 were on weekly dosing. The investigators also noted that 2 patients commenced adalimumab treatment in pregnancy at least 12 weeks before the earliest adalimumab level, 10 continued adalimumab throughout pregnancy, and 5 patients stopped between 30 and 33 weeks. All of the patients in this group were on remission at the time of included drug levels, and the median BMI, CRP, and fecal calprotectin levels showed no significant difference between trimesters 1 and 3, the study authors said. But like the infliximab group, median albumin levels in the adalimumab group decreased from 33.5 g/L in trimester 1 to 30.0 g/L in trimester 2, to 27.0 g/L in trimester 3.

A majority of the patients in the vedolizumab group received 300 mg, 8-weekly but 3 patients received 4-weeky, the study authors wrote. This group showed active disease during pregnancy in 6 of 17 patients, the study authors said, with 2 patients requiring prednisolone, 1 requiring antibiotics, and another who discontinued vedolizumab to 35 weeks gestation. A total of 12 patients had at least 2 observations during pregnancy, and the investigators found that of those, the medium number of intrapartum levels per patient was 3. There were no differences in paired levels between trimester 1 and 2, 2 and 3, or 1 and 3, the study authors said.

The study authors said most of the babies were delivered at full term with normal birth rates. They also determined there was strong positive correlation between infant vedolizumab levels and maternal vedolizumab levels at delivery, and infant vedolizumab levels at birth were all lower than their mother’s (with 2 exceptions). By 6-8 weeks in 4 infants and 10-15 weeks in 7 infants, vedolizumab was undetectable.

“This longitudinal study indicates that biological drugs used in patients with IBD differ in their altered clearance profiles during pregnancy,” the study authors concluded. “Adalimumab levels remain stable in pregnancy, while there can be a small increase in infliximab levels and decrease in vedolizumab levels during pregnancy. However, the alterations in concentrations predicted are small and unlikely to be of clinical significance regarding efficacy or toxicity.”