P420 Thiopurine metabolite testing to guide management in inflammatory bowel disease (IBD) yields clinical benefit at 12 months: A retrospective observational study.
S.-Y.J. Ooi1, M. Gounder2, R. Grafton1, P. Leach3, A. Sechi2, W. Ng2, S. Connor2, P. Bampton3, J.M. Andrews*1
1Royal Adelaide Hospital, Gastroenterology and Hepatology, Adelaide, Australia, 2Liverpool Hospital, Gastroenterology & Hepatology, Liverpool, Australia, 3Flinders Medical Centre, Inflammatory Bowel Disease Service, Bedford Park, Australia
Azathioprine & 6-mercaptopurine (AZA/MP) metabolites, 6-thioguanine nucleotides (6TGN) & 6-methyl-mercaptopurine (6MMP), are commonly measured. Cross-sectional observational data have led to a proposed "therapeutic range". Short-term studies support the use of therapeutic drug monitoring (TDM) to guide AZA/MP dosing and to identify "shunters" (preferential 6MMP producers). However, few data have evaluated TDM-led management in the longer-term. We therefore evaluated patient outcomes ≥12 months after AZA/MP TDM-led management in a large adult IBD cohort.
A multi-centre cross-sectional retrospective study was performed in 3 Australian IBD Services. Data were collected from clinical records of IBD adults, on AZA/MP for ≥4 weeks at index TDM. Patient demographics, disease characteristics, physician global assessment, IBD therapy at index TDM, and again ≥12 months after TDM-led management were collected. Indications for TDM were categorized. Therapeutic 6TGN was defined as 235-450pmol/8x108RBC. Shunters were defined as a 6MMP:6TGN ratio ≥11. Statistical analyses were performed using SAS 9.3.
343 patients were included for analysis. 247 (72%) had Crohn's disease (CD), 177 (52%) male, mean age 41 years, 218 (64%) had active disease at baseline. TDM was most commonly performed for proactive dose assessment (48%), flare (23%), ongoing active disease (21%) & adverse drug reactions (7%). Prior to TDM, 52% of patients would have had blind dose escalation, cessation of AZA/MP or escalation to another therapy. Overall, TDM led to continuation of AZA/MP ( ±dose adjustment ±allopurinol) in 290 (85%). At 12 months, 248/343 (72%) were in clinical remission, 19 (6%) improved disease activity, 67 (19%) active disease and 9 (3%) unknown activity status. Of the 267 with 12-month clinical remission/improvement, 157 (60%) achieved this with AZA/MP alone (±allopurinol). In comparison, this was achieved with anti-TNFα therapy, another medical agent, surgery in 61 (23%), 13 (4%) and 25 (9%) respectively. Univariate logistic regression analysis found only baseline remission to be a predictor of 12-month clinical remission/improvement on thiopurine therapy (OR 2.87, CI 1.20-6.89, p=0.02).
AZA/MP TDM-led management allows many patients apparently "failing" therapy to continue the agent and also identifies "shunters". TDM facilitates appropriate adjustment of therapy. TDM also promptly identifying those who require escalation to another agent or surgery, leading to an overall remission rate of 72% compared to 36% at baseline. AZA/MP±allopurinol alone achieved clinical remission in 60% of patients. This is the largest study to pragmatically evaluate longer-term outcomes of AZA/MP TDM and supports its clinical value.