6-thioguanine--efficacy and safety in chronic active Crohn's disease.

Abstract

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.

• Authors: K R Herrlinger, W Kreisel, M Schwab, J Schoelmerich, W E Fleig, A Ruhl, M Reinshagen, P Deibert, K Fellermann, R Greinwald, E F Stange
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 17 Issue 4 Pg. 503-8 (Feb 15 2003) ISSN: 0269-2813 [Print] England
• PMID: 12622758 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Mercaptopurine

Topics

• Adult
• Chronic Disease
• Crohn Disease (drug therapy)
• Dose-Response Relationship, Drug
• Female
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Male
• Mercaptopurine (administration & dosage, adverse effects)
• Middle Aged
• Prospective Studies
• Treatment Outcome