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P312. Thiopurine metabolite testing in inflammatory bowel disease

R. Goldberg1, G. Cunningham2, G. Moore1, J. Schulberg2, S. Brown2, W. Connell2, M. Lust2, M. Kamm2, S. Bell2, 1Monash University, Monash Health, Dept. of Gastroenterology, Melbourne, Australia, 2St Vincent's Hospital & University of Melbourne, Gastroenterology, Melbourne, Australia

Background

The thiopurines are established, cost effective therapies in IBD. However drug toxicity and lack of efficacy are significant problems. The traditional approach has been weight based dosing. More recently thiopurine metabolite testing has been introduced but it is unclear whether achieving a therapeutic level improves response. The aim of our study was to determine the predictive value of (1) clinical symptoms and (2) weight based dosing on metabolite levels and (3) the clinical utility of metabolite testing in a real world setting.

Methods

Metabolite tests were identified from pathology databases (2007–2012) at 2 tertiary IBD centers. Patients were included if they had taken a thiopurine for at least four weeks. Demographic data, reasons for testing, clinical status, action taken, and outcome were obtained by retrospective medical record review. Reference range: 6TGN levels 235–480, 6MMP <5700).

Results

169 patients were tested (117 Crohn's disease, mean dose Azathioprine 2.1 mg/kg, 6MP 1.1 mg/kg). Indications for testing were active disease despite weight based dosing (non-responders) (78%), adverse effects (18%) and suspected non-compliance (12%). Mean 6-TGN for patients tested due to active disease was 269 (0–1596), it was 404 (109–1496) for those tested due to adverse effects and 212 (0–522) for those tested due to non compliance.

(2) Analysis by current thiopurine dosing (mg/kg), divided patients into under target weight based dose (UD) vs at or greater than weight based dose (AD). There was no difference between UD compared with AD patients in the proportion who had therapeutic or supra-therapeutic 6-TGN levels (31.25% vs 31.7%). UD were more likely to have sub-therapeutic 6TGN levels ((54.7% vs 31.25%, p < 0.001) and less likely to be shunters (3.13% vs 21.95%, p < 0.0001). Metabolite testing resulted in a change to management (either dose change, re-enforced compliance or escalation of therapy) in 64% overall, but was most useful in those with non-response (68% vs. other 53% p = 0.03). Allopurinol was used in 6% prior to testing and 12% after metabolite testing. Repeat testing after allopurinol introduction showed reversal of shunting in 93% and a reduction in 6-MMP in 93% (p < 0.005), there was no significant change in 6-TGN following the addition of Allopurinol (p = 0.63).

Conclusion

Metabolite testing resulted in a change in management in patients not responding to thiopurines or experiencing adverse events. Sub therapeutic levels were the commonest finding suggesting under dosing and non-compliance were more common than clinically suspected. Weight based dosing does not seem to reliably result in therapeutic levels but when it is optimized is much more likely to result in shunting.