Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease
Article first published online: 15 DEC 2009
© 2010 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 31, Issue 6, pages 640–647, March 2010
How to Cite
ANSARI, A., PATEL, N., SANDERSON, J., O’DONOHUE, J., DULEY, J. A. and FLORIN, T. H. J. (2010), Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease. Alimentary Pharmacology & Therapeutics, 31: 640–647. doi: 10.1111/j.1365-2036.2009.04221.x
- Issue published online: 9 FEB 2010
- Article first published online: 15 DEC 2009
- Publication data Submitted 7 October 2009 First decision 25 October 2009 Resubmitted 11 December 2009 Accepted 11 December 2009 Epub Accepted Article 15 December 2009
Aliment Pharmacol Ther 31, 640–647
Background The thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently.
Aim To study combination of allopurinol with reduced-dose thiopurine in an attempt to avoid adverse drug reactions in the treatment of IBD.
Methods Patients with drug reactions to full-dose thiopurines were recruited for combination therapy in two IBD centres in this retrospective study. Dosing was guided by measuring thiopurine methyltransferase (for UK patients) or thioguanine nucleotides and methyl-6MP (Australian patients). Response was monitored by clinical activity indices.
Results Of 41 patients, 25 had non-hepatic and 16 had hepatitic reactions. Clinical remission was achieved in 32 patients (78%) with a median follow-up of 41 weeks (range 0.5–400). Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. The relative risk of having an adverse reaction with methyl-6MP in the top interquartile range was 2.7 (1.3–28) times that with methyl-6MP in the lower three quartiles (95% confidence interval).
Conclusion The combined experience from our centres is the largest reported experience of this combination therapy strategy in IBD, and the first to provide evidence for benefit in thiopurine and allopurinol co-therapy to avoid non-hepatitic adverse drug reactions.