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Antenatal thiopurine exposure in women with IBD is associated with intrahepatic cholestasis of pregnancy

Christian P. Selinger, Konstantina Rosiou, Giacomo Broglio, Gillian Lever, Chun Ming Chiu, Linden Stocker, Hlupekile Chipeta, Tracey Glanville

2023Expert Opinion on Drug Safety17 citationsDOI

Abstract

Background Pregnant women with inflammatory bowel disease (IBD) continue thiopurines to maintain remission. Other studies have reported intrahepatic cholestasis of pregnancy (ICP) in IBD pregnancies exposed to thiopurines. We aimed to investigate whether thiopurines are associated with an increased risk of ICP.Research design and methods Single-center retrospective cohort study comparing incidence of ICP in thiopurine-exposed versus non-exposed patients with IBD compared with age-matched pregnant controls.Results The IBD cohort consisted of 386 pregnancies in 243 patients with IBD, with 386 age-matched controls. In patients with IBD, ICP was significantly more common among thiopurine-exposed pregnancies (9.0% vs 1.8%; odds ratio [95% confidence interval] = 5.34 [1.78–16.02]; p = 0.021). IBD patients with thiopurine exposure were significantly more likely to experience ICP compared to non-IBD controls (9.0% vs 1.3%; p < 0.001). Patients with IBD not exposed to thiopurines had a comparable ICP incidence with controls (1.8% vs 1.3%; p = 0.75). Severe ICP occurred in 80% of thiopurine-exposed ICP cases versus 40% in non-exposed (p = 0.25), versus 20% in controls (p = 0.09).Conclusion Thiopurine exposure was associated with a significantly increased risk of ICP among patients with IBD compared to non-exposed IBD patients and age-matched general population controls. The course of ICP was not significantly different in thiopurine-exposed cases.

Topics & Concepts

Thiopurine methyltransferaseMedicineCholestasis of pregnancyInflammatory bowel diseaseInternal medicineOdds ratioGastroenterologyUlcerative colitisIncidence (geometry)PregnancyPopulationMercaptopurineCohortDiseaseFetusPhysicsOpticsEnvironmental healthBiologyGeneticsPregnancy and Medication ImpactAcute Lymphoblastic Leukemia researchInflammatory Bowel Disease