BACKGROUND: Thioguanine (TG) is efficacious in inflammatory bowel disease (IBD), but its toxicity, particularly nodular regenerative hyperplasia (NRH) of the liver, has limited its use. We assessed the long-term clinical outcomes and safety of TG in patients whom were intolerant or refractory to conventional immunomodulators. METHODS: This is a retrospective, single-centre study of IBD patients treated with TG from 2001-2013. Response was defined as clinical remission (Harvey-Bradshaw Index < 5 for Crohn's disease (CD), Simple Clinical Colitis Activity Index < 4 for ulcerative colitis (UC)) without corticosteroids or, if receiving anti-tumour-necrosis-factor (anti-TNF) therapy, absence of dose escalation. We recorded TG failure, withdrawal and adverse events. Patients were monitored with biochemistry, liver biopsy and/or magnetic resonance imaging (MRI). RESULTS: 54 patients (47 CD and 7 UC) whom received TG (mean dose: 27 mg/d (range: 20-40 mg/d)) as monotherapy (n = 36) or concomitantly with anti-TNF (n = 18) for a median inter-quartile range of 16 (5-37) months (126 patient-years of follow-up). 32 (59%) patients responded to TG at 6 months and 23 (43%) at 12 months. Pancreatitis did not recur amongst the 19 patients with prior thiopurine-induced pancreatitis. 16 (30%) patients ceased TG due to intolerance or toxicity (four serious); NRH was not observed. 6-thioguanine nucleotide concentrations did not correlate with efficacy nor with toxicity. CONCLUSIONS: TG was efficacious and well tolerated in one out of two patients who had previously failed conventional immunomodulators. NRH did not occur.
BACKGROUND:Thioguanine (TG) is efficacious in inflammatory bowel disease (IBD), but its toxicity, particularly nodular regenerative hyperplasia (NRH) of the liver, has limited its use. We assessed the long-term clinical outcomes and safety of TG in patients whom were intolerant or refractory to conventional immunomodulators. METHODS: This is a retrospective, single-centre study of IBDpatients treated with TG from 2001-2013. Response was defined as clinical remission (Harvey-Bradshaw Index < 5 for Crohn's disease (CD), Simple Clinical Colitis Activity Index < 4 for ulcerative colitis (UC)) without corticosteroids or, if receiving anti-tumour-necrosis-factor (anti-TNF) therapy, absence of dose escalation. We recorded TG failure, withdrawal and adverse events. Patients were monitored with biochemistry, liver biopsy and/or magnetic resonance imaging (MRI). RESULTS: 54 patients (47 CD and 7 UC) whom received TG (mean dose: 27 mg/d (range: 20-40 mg/d)) as monotherapy (n = 36) or concomitantly with anti-TNF (n = 18) for a median inter-quartile range of 16 (5-37) months (126 patient-years of follow-up). 32 (59%) patients responded to TG at 6 months and 23 (43%) at 12 months. Pancreatitis did not recur amongst the 19 patients with prior thiopurine-induced pancreatitis. 16 (30%) patients ceased TG due to intolerance or toxicity (four serious); NRH was not observed. 6-thioguanine nucleotide concentrations did not correlate with efficacy nor with toxicity. CONCLUSIONS:TG was efficacious and well tolerated in one out of two patients who had previously failed conventional immunomodulators. NRH did not occur.
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