TY - JOUR
T1 - Thioguanine in inflammatory bowel disease
T2 - Long-term efficacy and safety
AU - Ward, Mark G.
AU - Patel, Kamal V.
AU - Kariyawasam, Viraj C.
AU - Goel, Rishi
AU - Warner, Ben
AU - Elliott, Tim R.
AU - Blaker, Paul A.
AU - Irving, Peter M.
AU - Marinaki, Anthony M.
AU - Sanderson, Jeremy D.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
KW - Crohn’s disease
KW - thioguanine
KW - thiopurine
KW - toxicity
KW - ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85019610201&partnerID=8YFLogxK
U2 - 10.1177/2050640616663438
DO - 10.1177/2050640616663438
M3 - Article
AN - SCOPUS:85019610201
SN - 2050-6406
VL - 5
SP - 563
EP - 570
JO - United European Gastroenterology Journal
JF - United European Gastroenterology Journal
IS - 4
ER -