PWE-069 Measuring thioguanine nucleotide (6-TGN) levels and clinical response in IBD

Abstract

Introduction Monitoring levels of 6-TGN and titrating dose of Azathiopurine (AZA) and Mercaptopurine (6-MP) accordingly to achieve therapeutic concentrations of 6-TGN has been reported to improve outcomes in the treatment of Ulcerative colitis (UC) and Crohn’s Disease (CD). The aim of our study was to show how levels of 6-TGN corresponds to clinical outcome. Method This was a single centre (Royal Free Hospital), retrospective study, of patients receiving AZA or 6MP. We identified our patients by collating those who had been dispensed AZA or 6MP over the past 2 years. We were then able to access their electronic database, and record whether 6-TGN levels were subsequently taken to titrate treatment, and assess clinical outcome. Results 109 from 426 patients have so far been analysed (F=54 [50%]). UC=45 [41%] CD=64 [59%]. Mean duration on thiopurines was 7.6 years. Mean disease duration was 16.2 years. 74/109 (68%) had 6-TGN levels at some stage. 42/74 (57%) had therapeutic levels, whilst 32/74 (43%) did not. 49/74 (66%) were in clinical remission. 25/74 (34%) were not. Of those that had therapeutic levels of 6-TGN, 30/42 (71%) were in clinical remission. 7/30 (23%) were in total remission (clinical, biochemical [normal CRP/WCC], endoscopic and histological). 16/30 (53%) were on Azathiopurine (AZA), 14/30 (47%) were on mercaptapurine (6MP). 11/30 (37%) were on combined therapy with biologics. Of those that had non-therapeutic levels of 6-TGN, 19/32 (59%) were in clinical remission. 5/19 (26%) were in total remission. 12/19 (63%) AZA. 7/19 (37%) 6MP. 7/19 (37%) were on combined therapy. Of those with therapeutic levels of 6-TGN, 12/42 (29%) were not in clinical remission. 6/12 (50%) AZA, 6/12 (50%) 6MP. 8/12 (75%) were on combined therapy with biologics. Of the cohort that had non-therapeutic levels of 6-TGN, 13/32 (41%) were not in clinical remission. 6/13 (46%) AZA, 7/13 (44%) 6MP. 11/13 (85%) were on combined therapy Conclusion Our study so far suggests that, clinical remission rates were similar (71% vs. 59%) for those who had therapeutic 6-TGN levels and for those who had not. It also shows that even without achieving therapeutic levels of 6-TGN, 59% of patients were still in clinical remission. Our study interestingly highlights that even with therapeutic levels of 6-TGN and with three quarters of patients on combined biologics – 29% were still not in remission. This preliminary study suggests interesting trends, that will be assessed further across the entire population (n=426) and compared with European data.