RESUMEN
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 thiopurines. Objectives: We studied drug-survival of low dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines. Design: Retrospective observational study. Methods: All patients born 1956 and later, and who at least once started thiopurine treatment between 2006 and 2022 were included. A medical chart review was performed that noted drug-survival for every thiopurine treatment attempt. The Mantel-Cox rank test was used to test differences in drug-survival for different thiopurines. Blood chemistry analysis and faecal calprotectin levels were registered for the first 5 years of treatment. Results: In the study population, there was 379 initiated thiopurine treatments (210 for Crohn's disease and 169 for ulcerative colitis) in 307 patients with inflammatory bowel disease (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, thioguanine had the 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 thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: p = 0.006). At 60 months, 86% of the patients who started low-dose thioguanine were still on treatment compared to 42% of the patients who started 6-MP (p = 0.022). The median 6-thioguanine nucleotide levels in patients treated with thioguanine was 364 pmol/8 × 108. 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 showed significantly lower levels of FC in the third year of treatment compared to patient treated with azathioprine (59 versus 109 µg/g; p = 0.023), but there was no significant difference in FC levels for thioguanine compared to azathioprine (50 versus 109 µg/g; p = 0.33). Conclusion: Treatment with a low dose of thioguanine is well-tolerated in patients with IBD and had a significantly higher drug-survival than conventional thiopurines.
Low-dose of the immunomodulator drug thioguanine are well tolerated by patients with inflammatory bowel disease Thiopurines are commonly used to treat inflammatory bowel disease but it is common that patients end treatment due to side-effects. The thiopurine thioguanine has been suggested to be better tolerated than other thiopurines. We aimed to study if a low-dose of thioguanine had been tolerated better and used longer than other thiopurines in patients with inflammatory bowel disease at our clinic. In the study population there was 379 initiated thiopurine treatments in 307 patients with inflammatory bowel disease. Among those patients a low-dose thioguanine had been initiated in 31 patients. Overall, when including all thiopurine attempts, thioguanine had longest drug-survival of all thiopurines. For second line thiopurine treatment thioguanine had longer drug-survival than the thiopurine 6-mercaptopurine that are usually used as second line thiopurine treatment. 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-mercaptopurine.There was a similar response on inflammatory markers the first five years from starting treatment with thioguanines compared to conventional used thiopurines. We conclude that treatment with a low-dose of thioguanine is well tolerated in patients with inflammatory bowel disease and have a significantly higher drug survival than conventional thiopurines.
