P321 On effectiveness, safety, and TDM of thioguanine in a cohort of 274 patients with IBD, intolerant for conventional thiopurines
M. Simsek*1, D. Deben2, C. S. Horjus3, M. Seinen1, C. J. Mulder1, D. R. Wong2, N. K. de Boer1, A. A. van Bodegraven4
1Amsterdam UMC, VU Medical Center, Gastroenterology and Hepatology, Amsterdam, The Netherlands, 2Zuyderland Medical Center, Clinical Pharmacy, Sittard-Geleen-Heerlen, The Netherlands, 3Rijnstate Hospital, Gastroenterology and Hepatology, Arnhem, The Netherlands, 4Zuyderland Medical Center, Gastroenterology and Hepatology, Sittard-Geleen-Heerlen, The Netherlands
Thioguanine (TG) has been considered as an alternative drug in patients with inflammatory bowel disease (IBD) who failed prior conventional immunomodulating therapy. In this study, we report on effectiveness, safety and therapeutic drug monitoring (TDM) data of an intercept cohort of patients with prolonged TG maintenance therapy.
In this nationwide, multi-centre study, medical records of TG using IBD patients were retrospectively reviewed. Both patient and drug characteristics as well as effectiveness and safety profile of TG therapy were assessed. Beneficial effect of therapy was defined as clinical remission, without (re)initiation of corticosteroids, concurrent biological therapy or surgical intervention. All adverse events (AE) which occurred during follow-up were listed and graded according to the common terminology criteria (CTCAE).
In total, 274 patients (female 63% and Crohn’s disease in 68%) were included with a median daily dosage of 20 mg (range 8–40 mg), median treatment duration of 51 months (IQR 36–89) and 1567 patient-years of follow-up. The beneficial therapeutic response to TG therapy was documented in 66% of patients within 6 months. A sustained clinical benefit of more than 1 year was observed in 51% of patients and 72% continued TG until end of follow-up. About 40% of patients developed AE during TG therapy of which 5% were graded as severe according to the CTCAE. Twenty-nine patients (11%) discontinued TG due to intolerance or severe AE. Infections requiring hospitalisation occurred in three (1.1%), non-melanoma skin cancer in six (2.2%) and melanoma in two patients (0.7%). Portal hypertension was found in three (1.1%) and NRH in two patients (0.7%). None of the patients developed pancreatitis including 43 patients (16%) with prior azathioprine or mercaptopurine-induced pancreatitis. Beneficial therapeutic response was correlated with 6-thioguanine-nucleotide (6-TGN) threshold levels of > 682 pmol/8 × 108 RBC (
Long-term TG therapy was effective and well-tolerated as a maintenance treatment for IBD in about 70% of patients, continuing TG during a median treatment time of more than 4 years. Adverse events were not uncommon, but were mainly tolerable and of limited severity. An approximate 6-TGN threshold level of ≥ 700 pmol/8 × 108 RBC was associated with beneficial therapeutic response.