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

Expert Opin Drug Saf. 2023 Jul-Dec;22(11):1091-1097. doi: 10.1080/14740338.2023.2234813. Epub 2023 Jul 10.

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.

Keywords: Inflammatory bowel disease; azathioprine; intrahepatic cholestasis; pregnancy; thiopurines.

MeSH terms

  • Azathioprine* / adverse effects
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Inflammatory Bowel Diseases* / chemically induced
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / drug therapy
  • Mercaptopurine / adverse effects
  • Pregnancy
  • Retrospective Studies

Substances

  • Azathioprine
  • Mercaptopurine
  • Immunosuppressive Agents

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy