Thioguanine in inflammatory bowel disease: Long-term efficacy and safety. Issue 4 (June 2017)

• Record Type: Journal Article
• Authors: Ward, Mark G; Patel, Kamal V; Kariyawasam, Viraj C; Goel, Rishi; Warner, Ben; Elliott, Tim R; Blaker, Paul A; Irving, Peter M; Marinaki, Anthony M; Sanderson, Jeremy D
• Is Part Of: United European Gastroenterology journal. Volume 5:Issue 4(2017)
• Page Start: 563
• Page End: 570
• Publication Date: 2017-06
• Subjects: Crohn's disease -- thioguanine -- thiopurine -- toxicity -- ulcerative colitis; Gastroenterology -- Periodicals; Periodicals; 616.33005
• DOI: 10.1177/2050640616663438
• Languages: English
• ISSNs: 2050-6406

Abstract

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.