Premium
6‐Thioguanine — efficacy and safety in chronic active Crohn's disease
Author(s) -
Herrlinger K. R.,
Kreisel W.,
Schwab M.,
Schoelmerich J.,
Fleig W. E.,
Ruhl A.,
Reinshagen M.,
Deibert P.,
Fellermann K.,
Greinwald R.,
Stange E. F.
Publication year - 2003
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2003.01440.x
Subject(s) - medicine , azathioprine , crohn's disease , gastroenterology , adverse effect , mercaptopurine , refractory (planetary science) , pancreatitis , inflammatory bowel disease , disease , physics , astrobiology
Summary Background : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side‐effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6‐thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6‐thioguanine in chronic active Crohn's disease. Methods : Thirty‐seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence ( n = 19), steroid refractoriness ( n = 9) and/or intolerance ( n = 16) or refractoriness ( n = 6) to azathioprine. Patients were treated with 40 mg/day of 6‐thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index. Results : In the intention‐to‐treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty‐seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 ± 74 to 153 ± 101. 6‐Thioguanine was more effective in azathioprine‐intolerant than in azathioprine‐refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6‐thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia. Conclusions : In this patient group with chronic active Crohn's disease, 6‐thioguanine appeared to be effective with acceptable short‐term toxicity, but long‐term controlled trials are clearly needed to further define its role.