Poor Response to Thiopurine in Inflammatory Bowel Disease: How to Overcome Therapeutic Resistance?

A 24-year-old woman (53 kg) with a 5-year history of steroid-dependent ulcerative colitis with mild and ex-tensive ulcerations presented to the gastroenterology clinic for symptom recurrence. She was given 100 mg/ day (1.9 mg kg1 day1) azathioprine (AZA)5 for 1 month, after which the dose was increased to 125 mg/ day (2.3 mg kg1 day1). Four months later, the pa-tient was tapered off steroid therapy. Her symptoms persisted after 7 months of AZA therapy, however, and she experienced gastrointestinal side effects. The pa-tient was switched to another thiopurine drug, 6-mercaptopurine (6-MP), at 75 mg/day (1.4 mg kg1 day1), which was well tolerated but simi-larly ineffective (8 stools daily). A brief course of ste-roid therapy rapidly produced a substantial but short