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P186. Outcomes of patients with Crohn's disease: azathioprine tolerant and azathioprine intolerant

L.Y. Lee1, A. Gardezi1, T. Shaul1, D. Wilton1, P. Patel1, G. Macfaul1, S. Lanzon-Miller1, 1Milton Keynes NHS Foundation Trust, Milton Keynes, United Kingdom

Background

Azathioprine is well established for maintenance of remission in patients with Crohn's disease. 87% patients on therapy are able to reduce steroid consumption, however, seven patients need to be treated with azathioprine to prevent one recurrence [1]. Intolerance to azathioprine occurs in a third of patients and it has been proposed that intolerance is a poor prognostic marker that predisposes to a more aggressive disease course.

Methods

A cross sectional study was performed using the Milton Keynes Hospital IBD database to compare outcomes of patients that were azathioprine intolerant to those that were tolerant. A descriptive analysis of clinical features and outcomes of these two groups was performed. Disease activity scores were based on the Harvey Bradshaw index.

Results

141 patients were included for analysis of which 24.8% were intolerant to azathioprine. The median age of azathioprine intolerant patients was 47 and 31.4% were male. In the azathioprine tolerant cohort, the median age was 36 and 41.5% were male. Azathioprine was not tolerated due to gastrointestinal side effects in 53.6%, neurological effects (depression/headaches/vertigo) in 17.9%, deranged LFTs in 17.9% and the arthralgia/neutropenia and cutaneous side effects making up the remaining cases.

 Azathioprine intolerant (n = 35)Azathioprine tolerant (n = 106)
No. requiring surgery (%)13 (37.1)55 (51.8)
No. with strictures/fistula (%)17 (48.6)63 (59.4)
No. with extensive disease (%)3/30 (10)11/92 (12.0)
Disease activity  
 No. in remission (HBI <5)19/34 (55.9)76/96 (79.2)
 No. with mild disease (HBI 5–7)7/34 (20.6)17/96 (17.7)
 No with moderate-severe disease (HBI >7)8/34 (23.5)3/96 (3.1)
No. steroid dependent7 (20.0)2 (1.9)
No. requiring anti-TNF agents9 (25.7)13 (12.3)

Conclusion

Azathioprine is a drug that is not tolerated in nearly a quarter of Crohn's disease patients. The most likely reason for azathioprine intolerance was gastrointestinal side effects. Patients who were intolerant were not more likely to undergo surgery or to develop strictures or fistulas. However, intolerant patients were considerably more likely to have active disease, to require anti-TNF therapy and steroids. Compared to patients who are able to use azathioprine, for every 100 patients who are intolerant, 24 less will be in remission and 20 more will have moderate to severe disease. We conclude that patients with azathioprine intolerance will have poorer symptom control, but are not predisposed to a more aggressive disease course.

1. Pearson D, May G, Sutherland L, (1996), Azathioprine for maintenance of remission in Crohn's disease, Cochrane Database of Systematic Reviews.