Thioguanine therapy during pregnancy in inflammatory bowel diseases

Since 1962, the conventional thiopurines, mercaptopurine (MP) and its prodrug azathioprine (AZA), have been used in the treatment of ulcerative colitis and Crohn’s disease, together known as inflammatory bowel diseases (IBD).1,2 In recent times, a third thiopurine-derivative named thioguanine (TG) is increasingly being used as a ‘rescue’ drug in IBD-patients who had to discontinue AZA or MP therapy due to intolerance or resistance (up to 50% in the first two years of treatment).3 Thioguanine treatment has shown promising short-term results with regards to safety and effectiveness in patients with IBD, and has recently been provisionally re-registered (name: Thiosix®) for IBD in The Netherlands.4-6

Ulcerative colitis and Crohn’s disease predominantly affect young adults, including a significant number of female patients in their reproductive years.7 Active disease during pregnancy has been linked to poor reproduction capacity and pregnancy outcome (i.e. low birthweight and premature birth), emphasizing the importance of disease control prior to and throughout pregnancy. Azathioprine and MP are considered safe during pregnancy and breastfeeding, despite detectable metabolite concentrations in the newborn and breastmilk.8,9 Relatively less is known about the pharmacological aspects of TG therapy during pregnancy and its effects on maternally exposed offspring. In one descriptive case series consisting of 19 pregnancies, the relatively safe use of TG in pregnant IBD-patients was described.10 Larger studies are needed to confirm these findings and in order to counsel patients appropriately about conception and pregnancy during TG therapy for IBD. Additionally, knowledge about the long-term effects of maternally TG exposure is essential.

Therefore the objective of this study is to assess the safety of TG in maternally exposed offspring, as well as to collect data on the long-term development outcomes of these exposed children.

Based on a small cohort study of 19 pregnancies with healthy infants, we hypothesize that thioguanine exposure during pregnancy is relatively safe for the fetus.

Data will be collected after child birth

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