Further experience with the use of 6-thioguanine in patients with Crohn's disease.
BACKGROUND
6-Thioguanine (6-TG) is efficacious in patients with Crohn's Disease (CD) failing conventional immunosuppression but there are reports of hepatotoxicity. We report our experience of the safety and efficacy of 6-TG in a series of patients with CD.


METHODS
A retrospective study of patients with CD who failed thiopurines +/- methotrexate between 2001 and 2006 was performed. Indications for 6-TG were; active disease, to allow infliximab withdrawal, steroid sparing, or fistula closure. Patients underwent regular review and those treated longer than 1 year were advised to have liver magnetic resonance imaging (MRI) and liver biopsy.


RESULTS
All 30 patients treated with 6-TG during the period were included. The median dose and duration of 6-TG was 40 mg daily and 21.5 months, respectively. Initial clinical response was achieved in 18/30 (60%). Eleven of 29 (38%) (1 unrelated death) remained in remission at a median 44 months follow-up. Seven of 30 (23%) discontinued 6-TG due to adverse effects; 7/30 (23%) patients developed abnormal liver function tests (LFTs) during treatment, mostly transient and mild. One patient developed a portal hypertensive syndrome resolving on cessation of 6-TG. Of 11 liver biopsies, none showed nodular regenerative hyperplasia (NRH). The median red blood cell 6-thioguanine nucleotide (6-TGN) level was 807 pmol/10(8).


CONCLUSIONS
6-TG has good clinical efficacy for third-line immunosuppression in CD but hepatotoxicity remains a concern. However, previous reports of NRH in 6-TG-treated inflammatory bowel disease patients have not been substantiated by this cohort.
Department of Gastroenterology, Guy's & St. Thomas' Hospitals NHS Foundation Trust, London SE1 7EH, United Kingdom.
Azhar
A
Ansari
Tim
T
Elliott
Farina
F
Fong
Monica
M
Arenas-Hernandez
Giles
G
Rottenberg
Bernard
B
Portmann
Sebastian
S
Lucas
Anthony
A
Marinaki
Jeremy
J
Sanderson
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006975:Hypertension, Portal / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008111:Liver Function Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012074:Remission Induction / Q000379:methods*; D012189:Retrospective Studies; D012449:Safety; D013866:Thioguanine / Q000009:adverse effects* / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D013866:Thioguanine