Introduction Failure of Thiopurine (TP) therapy could be said to be the gatekeeper to unwanted outcomes in Inflammatory Bowel Disease (IBD) as it often leads to treatment with costlier anti-TNF’s, higher steroid use and hospitalisations that could be reduced by improvement of response to TP therapy. Current use of low-dose Azathioprine (AZA) or 6 mercaptopurine (6 MP) with allopurinol (LDAA) has restricted its use to a patient group with a selected TP metabolite profiles: 15% of TP non-responders and 50% of hepatotoxic patients. A review of current literature of LDAA in IBD will be compared to our own experiences at East Surrey Hospital (ESH) where metabolite profiling is not used to assess differences in outcomes.
Methods A search of MEDLINE and EMBASE between January 2010 and February 2014 was performed to yield investigations of treatment with LDAA in IBD. Studies and participant numbers that use metabolite profiling prior to treatment with LDAA will be compared by response rates (achievement of steroid free remission (SFR)), to studies that use LDAA treatment without metabolite profiling. Only studies with robust numbers of participants will be considered in this preliminary investigation.
Results Searches identified 27 studies (14 complete papers, 8 abstracts, 5 case reports) of LDAA co-therapy. In total, 244 IBD patients came from studies that restricted use of LDAA co-therapy by metabolite profiling. The two largest studies Smith et al. 2012 JCC (n = 110) and Hoentjen et al. 2013 IBD (n = 77) showed SFR rates of 76% and 65% respectively. 368 patients were treated with LDAA without metabolite profiling allowing universal access where TP’s are clinically indicated. The largest study came from ESR Stamoulos et al. 2011 Gut (n = 300), and saw comparable SFR rates of 70%, comparable rates were also seen in smaller studies.
Conclusion Metabolite profiling creates an unnecessary barrier to treatment with LDAA. SFR rates appear comparable between the two groups, thus drawing in to question the utility of this selection tool. Data from ESR suggests that a majority proportion of patients with the potential to benefit from LDAA (approximately 59%) will be screened out and moved to alternative costlier treatment pathways on the NHS. A paradigm shift in thinking is necessary to address the compulsion of metabolite profiling prior to LDAA therapy and whether it offers any true benefit for the patient; our experience suggests perhaps not and warrants further investigation.
Disclosure of Interest None Declared
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