P592 Effectiveness and safety of thioguanine in thiopurine-naïve Inflammatory Bowel Disease patients

Crouwel, F.(1);Bayoumy, A.B.(1);Mulder, C.J.J.(1);Peters, J.H.C.(2);Boekema, P.J.(3);Derijks, L.J.J.(4);De Boer, S.Y.(5);van de Meeberg, P.C.(5);Ahmad, I.(6);Buiter, H.J.C.(7);de Boer, N.K.(1);

(1)Amsterdam UMC- location VUmc, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(2)Rode Kruisziekenhuis, Department of Gastroenterology and Hepatology, Beverwijk, The Netherlands;(3)Maxima Medical Centre, Department of Gastroenterology and Hepatology, Veldhoven, The Netherlands;(4)Maxima Medical Centre, Department of Clinical Pharmacy and Pharmacology, Veldhoven, The Netherlands;(5)Slingeland Hospital, Department of Gastroenterology and Hepatology, Doetinchem, The Netherlands;(6)Streekziekenhuis Koningin Beatrix, Department of Gastroenterology and Hepatology, Winterswijk, The Netherlands;(7)Amsterdam UMC- location VUmc, Department of Radiology and Nuclear Medicine, Amsterdam, The Netherlands;


Currently thioguanine is considered as off-label rescue therapy for Inflammatory Bowel Disease (IBD) after conventional thiopurine failure. This study aimed to determine the safety, effectiveness and 12-month drug tolerability of thioguanine in thiopurine-naïve IBD patients.


We performed an analysis of our multicenter, retrospective cohort study including thiopurine-naïve IBD patients treated with thioguanine as first-line maintenance therapy without concomitant biological therapy. Clinical effectiveness was defined as a sustained clinical response (based on physician’s global assessment) without the (re-)initiation of concurrent biological therapy, corticosteroids or a IBD-related surgical intervention. All adverse events that occurred during follow-up were categorized by the Common Terminology Criteria for Adverse Events. Elevation of two concurrent liver tests were categorized as drug-induced liver injury.


A total of 103 IBD patients (female 61%, Crohn’s disease 52%) were included with a median daily thioguanine dose of 20mg and median 6-thioguanine nucleotide (6-TGN) levels of 635 pmol/8x108 RBC (IQR 425–1100). Clinical effectiveness at 12 months was observed in 60 out of 99 patients (61%) and 80% of patients were still using thioguanine 12 months after initiation. Four patients did not reach the 12-month follow-up period but were in remission at time of data collection. Of the responding patients at 12 months 88% (N=53) remained responsive until the end of follow-up (median follow-up period 28 months, IQR 17–40 months).

Forty-nine patients (48%) developed adverse events (grade 1 or 2), of which 24% graded as moderate (grade 2) and none as severe. Seven patients ceased therapy due to the occurrence of adverse events. Adverse events consisted mainly of elevated liver tests (26%) and gastrointestinal complaints (17%). An infection was documented in three patients, none of them requiring hospitalization. Pancytopenia occurred in two other patients with 6-TGN levels of respectively 2900 and 140 pmol/8x108 RBC. None of the included patients had signs of (noncirrhotic) portal hypertension or underwent a liver biopsy during follow-up.


This is the first cohort study that reports on the safety and effectiveness of first-line thioguanine maintenance therapy in IBD. Thioguanine therapy was, 12 months after initiation, still used by 80% and clinically effective in 61% of thiopurine-naive patients. Adverse events were relatively common but mainly mild (grade 1) and the discontinuation rate related to adverse events was lower than observed during conventional thiopurine therapy. No signs of (noncirrhotic) portal hypertension were reported