Effect of azathioprine intolerance on outcomes of inflammatory bowel disease: a cross-sectional study

Azathioprine is well established for the maintenance of remission in patients with inflammatory bowel disease (IBD). However, a significant proportion of patients are intolerant to azathioprine. It is not clear if intolerance of azathioprine is a marker of poor prognosis for patients who will have a more aggressive disease or be more likely to require surgery.

To determine if intolerance to azathioprine is a marker of poor prognosis, indicating patients who have a more aggressive disease course, and to analyse the risk factors and causes of intolerance.

A cross-sectional study using the Milton Keynes Hospital IBD database was performed to compare azathioprine-intolerant and azathioprine-tolerant patients.

Two hundred and thirty-nine patients met the inclusion criteria comprising 141 patients with Crohn's disease (CD) and 98 patients with ulcerative colitis (UC). Overall, 28.0% of patients were intolerant to azathioprine. Risk factors for intolerance were female sex and age 50-70 years. Common reasons for intolerance were nausea and vomiting (34.3%), deranged liver function tests (28.4%) and headaches (11.9%). In patients with UC, there was no statistical difference in the disease activity scores between those who were azathioprine intolerant versus tolerant. In patients with CD, azathioprine intolerance was associated with significantly worse disease activity; 25% fewer patients were in clinical remission and 20% more had moderate/severe disease. Rates of surgery were similar between the groups for both UC/CD.

We conclude that azathioprine intolerance acts as a surrogate marker for patients with CD who in future have poorer symptom control. Azathioprine intolerance marks out a group of patients with CD in whom increased vigilance of symptom control and early escalation of treatment is required.