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

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
• pregnancy
• intrahepatic cholestasis
• thiopurines
• azathioprine

Declaration of interest

CP Selinger has received unrestricted research grants from Warner Chilcott, Janssen, and AbbVie; has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda, Fresenius Kabi, Galapagos, Ferring, Arena, and Janssen; and had speaker arrangements with Warner Chilcott, Dr Falk, AbbVie, MSD, Pfizer, Celltrion, and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

CP Selinger designed the study. CP Selinger, K Rosiou, G Rosiou, and L Stocker collected the data. CP Selinger performed the analysis. All authors interpreted the results. CP Selinger wrote the draft manuscript. All authors critically reviewed the draft manuscript and approved the final manuscript.

Data availability statement

Summary data are available on request.

Additional information

Funding

This paper was not funded.