Further experience with the use of 6-thioguanine in patients with Crohn's disease

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Background:6-Thioguanine (6-TG) is efficacious in patients with Crohn's Disease (CD) failing conventional immunosuppression but there are reports of hepatotoxicity. We report our experience of the safety and efficacy of 6-TG in a series of patients with CD.Methods:A retrospective study of patients with CD who failed thiopurines ± methotrexate between 2001 and 2006 was performed. Indications for 6-TG were; active disease, to allow infliximab withdrawal, steroid sparing, or fistula closure. Patients underwent regular review and those treated longer than 1 year were advised to have liver magnetic resonance imaging (MRI) and liver biopsy.Results:All 30 patients treated with 6-TG during the period were included. The median dose and duration of 6-TG was 40 mg daily and 21.5 months, respectively. Initial clinical response was achieved in 18/30 (60%). Eleven of 29 (38%) (1 unrelated death) remained in remission at a median 44 months follow-up. Seven of 30 (23%) discontinued 6-TG due to adverse effects; 7/30 (23%) patients developed abnormal liver function tests (LFTs) during treatment, mostly transient and mild. One patient developed a portal hypertensive syndrome resolving on cessation of 6-TG. Of 11 liver biopsies, none showed nodular regenerative hyperplasia (NRH). The median red blood cell 6-thioguanine nucleotide (6-TGN) level was 807 pmol/108.Conclusions:6-TG has good clinical efficacy for third-line immunosuppression in CD but hepatotoxicity remains a concern. However, previous reports of NRH in 6-TG-treated inflammatory bowel disease patients have not been substantiated by this cohort.

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