Safety of biosimilar infliximab in pregnant women with IBD Posted 11/05/2018

Introduction of the first biosimilar infliximab (CT‑P13, Remsima/Inflectra) for the treatment of inflammatory bowel diseases (IBDs) was aimed to reduce the healthcare cost burden and to increase the number of treated individuals with similar treatment results. Shortly after CT‑P13 has been authorized for usage in clinical practice, many concerns arose due to the fact that the principle of extrapolation of limited clinical results had been applied to the biosimilar, which led to approval of the biosimilar in all the indications of the originator biological (Remicade). However, these concerns have proved to be unfounded, as subsequent studies have confirmed the similar efficacy, safety and immunogenicity of CT‑P13 and Remicade in the general IBD population [1].

However, data on the safety of infliximab in pregnant women have long been conflicting, mainly due to the small sample sizes of the studies and the drug was thus labelled as pregnancy category B by the US Food and Drug Administration (FDA). As an IgG1 monoclonal antibody, infliximab is actively transported across placenta with an exponential growth of concentration in foetal blood during the third trimester of pregnancy. While the negative effect of the originator drug still cannot be absolutely ruled out, especially from the point of view of long-term healthy development of the exposed children, it is considered that benefit of treatment outweighs potential harm, since the majority of more recent studies have confirmed no association between anti-tumour necrosis factor (TNF) therapy during pregnancy and adverse pregnancy outcomes. However, until now, it was an open question whether the same applies also to biosimilar infliximab.

The retrospective study by Kolar et al. [2] focused on evaluation of pregnancy outcomes of women with IBD treated with biosimilar infliximab during pregnancy. The study included 20 consecutive female patients with Crohn’s disease (CD) and ulcerative colitis (UC) who became pregnant while being treated with biosimilar infliximab. Disease state was evaluated using Physician’s Global Assessment as either remission or active disease and data on C-reactive protein (CRP) and faecal calprotectin (FC) were retrieved from the individual visits. Data on pregnancy outcome included gestational age, presence of congenital defects, and weight and height of the newborn. At the time of delivery, maternal and cord blood samples were collected to measure trough levels of biosimilar infliximab and anti-infliximab antibodies.

Twenty recorded pregnancies resulted in 19 live births. One case ended in spontaneous abortion. Only five deliveries (26.3%) were vaginal, while 14 (73.7%) were using C-section. All section deliveries occurred in women with CD, 11 of whom had a history of perianal disease. All but one live births were at full-term, with mean 39.0±1.3 weeks of gestation. A single case of pre-term birth was registered (36 weeks) and this birth also resulted in a newborn with low birth weight. Mean birth weight of all newborns was 3,305±493 g. Congenital defect was detected in one case and included cleft palate. No perinatal complications were registered. Comparing birth weights of newborns born to mothers in remission and mothers with active disease, newborns of mothers with active disease at conception had significantly lower birth weight (2,921±390 g vs 3,549±392 g; p = 0.0043).

The detected newborn infliximab levels at delivery were 11.2±15.0 µg/mL with last dose administration 12.1±6.6 weeks before delivery. Corresponding maternal levels were 7.8±15.0 µg/mL. The time to delivery since last administration was negatively correlated with cord blood infliximab levels (rS = -0.6759; p = 0.0069). Numerical increase in CRP in both patients with active disease and in remission was observed, however, patients with active IBD could have been identified by significantly higher CRP, particularly during pregnancy. FC remained stable and low in patients in remission and was higher in patients with active disease during all visits.

The results suggest that, although there was a limited sample size, the use of biosimilar infliximab with regard to pregnancy outcomes is safe. Moreover, it can be underscored that maintaining disease remission during conception and pregnancy is crucial for the pregnancy outcome, since, even in a small study of 20 subjects, the newborns of mothers with active disease at the time of conception had significantly lower birth weight compared to those born to mothers in remission. This provides an eventual rationale for continuing infliximab throughout the whole course of pregnancy, even though it is normally interrupted at the end of second trimester.

Conflict of interest
The authors of the research paper [2] declared that there was no conflict of interest.

Abstracted by Martin Kolar, IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic.

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1.  Kolar M, Duricova D, Bortlik M, et al. Biosimilar infliximab in anti-TNF-naïve IBD patients -1-year clinical follow-up. Gastroent Hepatol. 2016;70(6):514-22.
2.  Kolar M, Bortlik M, Duricova D, et al. Pregnancy outcomes in women with IBD treated with biosimilar infliximab. Gastroent Hepatol. 2018;72(1):20-6.

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