P906 The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease. A retrospective observational study

Abstract

Abstract Background Thiopurines are commonly used to treat inflammatory bowel disease but withdrawal due to side-effects are common. Thioguanine has been suggested to be better tolerated than conventional thiopuries. We aimed to study drug-survival of low-dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines. Methods All patients born in the year 1956 and later, and who at least once started thiopurine treatment between the years 2006-2022 were included. A medical chart review was performed that noted drug-survival for every thiopurine treatment attempt. Mantel-Cox rank test was used to test differences in drug-survival for different thiopurines. Blood chemistry analysis and faecal calprotectin levels was registered the first five years of treatment. Results In the study population there was 379 initiated thiopurine treatments (210 for Crohns disease and 169 for ulcerative colitis) in 307 patients with IBD. Low-dose thioguanine (median dose 11 mg; 25-75th percentile 7-19 mg) had been initiated in 31 patients. Overall, when including all thiopurine attempts, the median time on treatment for the different thiopurine treatments were for azathioprine 24 months (25th-75th percentile 3-59 months), for 6-mercaptopurine 15 months (3-59 months), for azathioprine/allopurinol 22 months (1-25 months) and for thioguanine 33 months (11-64 months). Thioguanine had longest drug-survival (Mantel-cox rank test: thioguanine versus azathioprine p=0.014; thioguanine versus 6-mercaptopurine (6-MP) p<0.001). For second line thiopurine treatment, the median time on treatment for 6-mercaptopurine were 13 months (2-69) and for thioguanine 33 months (11-64). Thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: p=0.006) (Figure). At 60 months, 86% of the patients who started low dose thioguanine was still on treatment compared to 42% of the patients who started 6-MP (p=0.022). The median 6-TGN levels in patients treated with thioguanine was 364 pmol/8x108. Patients on thioguanine treatment showed significantly lower values of median mean corpuscular volume at follow-up than patients treated with azathioprine and 6-MP. Patients treated with 6-MP had signficantly lower levels of F-calprotectin at year three and year four compared to patients treated with azathioprine. Overall there was a similar response on inflammatory markers the first five years from starting treatment with thioguanines compared to conventional thiopurines. Conclusion Treatment with a low-dose of thioguanine is well tolerated in patients with IBD and have a significantly higher drug survival than conventional thiopurines.