Impact of thiopurines and tumour necrosis factor antagonists on primary sclerosing cholangitis outcomes in patients with inflammatory bowel disease

Aliment Pharmacol Ther. 2022 Sep;56(5):857-868. doi: 10.1111/apt.17123. Epub 2022 Jul 4.

Abstract

Background: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are at risk of biliary tract cancer and liver damage (possibly leading to liver transplantation), and are often treated for IBD with thiopurines and/or tumour necrosis factor antagonists (anti-TNF) on a long-term basis.

Aims: To assess the risk of biliary tract cancer and liver transplantation in patients exposed to thiopurines and/or anti TNF agents in a French nationwide cohort.

Methods: We performed a population-based study of patients aged 18 years or older with PSC and IBD in the French national health insurance database. Patients were followed from 1 January 2009 to 31 December 2018. The risks of biliary tract cancer and liver transplantation associated with thiopurines and anti-TNF exposure were assessed with marginal structural Cox proportional hazard models, adjusting for baseline demographics and comorbidities, and time-varying medications and PSC activity.

Results: Among the 1929 patients with PSC and IBD included, 37 biliary tract cancers and 83 liver transplantations occurred. Compared with patients not exposed to thiopurines or anti-TNF agents, patients exposed to thiopurines (hazard ratio [HR], 1.05; 95% confidence interval [CI], 0.39-2.82) or anti-TNF agents (HR, 0.59; 95% CI, 0.13-2.80) had no excess risk of biliary tract cancer. Similarly, patients exposed to thiopurines (HR, 0.67; 95% CI, 0.30-1.48) or anti-TNF agents (HR, 0.68; CI, 0.22-2.09) had no excess risk of liver transplantation.

Conclusions: Patients with PSC and IBD who are exposed to thiopurines or anti-TNF agents are not at excess risk of biliary tract cancer or liver transplantation.

Keywords: anti-TNF; biliary tract cancer; inflammatory bowel disease; primary sclerosing cholangitis; thiopurines.

MeSH terms

  • Cholangitis, Sclerosing* / complications
  • Cholangitis, Sclerosing* / drug therapy
  • Humans
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / drug therapy
  • Liver Transplantation* / adverse effects
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Tumor Necrosis Factor Inhibitors / adverse effects

Substances

  • Tumor Necrosis Factor Inhibitors