Helena Gensmyr-Singer, Mårten Werner, Pontus Karling
{"title":"炎症性肠病患者小剂量硫鸟嘌呤的药物存活率:一项回顾性观察研究。","authors":"Helena Gensmyr-Singer, Mårten Werner, Pontus Karling","doi":"10.1177/17562848241228064","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>We studied drug-survival of low dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines.</p><p><strong>Design: </strong>Retrospective observational study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>versus</i> azathioprine <i>p</i> = 0.014; thioguanine <i>versus</i> 6-mercaptopurine (6-MP) <i>p</i> < 0.001]. For second-line thiopurine treatment thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: <i>p</i> = 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 (<i>p</i> = 0.022). The median 6-thioguanine nucleotide levels in patients treated with thioguanine was 364 pmol/8 × 10<sup>8</sup>. 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 <i>versus</i> 109 µg/g; <i>p</i> = 0.023), but there was no significant difference in FC levels for thioguanine compared to azathioprine (50 <i>versus</i> 109 µg/g; <i>p</i> = 0.33).</p><p><strong>Conclusion: </strong>Treatment with a low dose of thioguanine is well-tolerated in patients with IBD and had a significantly higher drug-survival than conventional thiopurines.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":"17 ","pages":"17562848241228064"},"PeriodicalIF":3.9000,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880529/pdf/","citationCount":"0","resultStr":"{\"title\":\"The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease: a retrospective observational study.\",\"authors\":\"Helena Gensmyr-Singer, Mårten Werner, Pontus Karling\",\"doi\":\"10.1177/17562848241228064\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>We studied drug-survival of low dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines.</p><p><strong>Design: </strong>Retrospective observational study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>versus</i> azathioprine <i>p</i> = 0.014; thioguanine <i>versus</i> 6-mercaptopurine (6-MP) <i>p</i> < 0.001]. For second-line thiopurine treatment thioguanine had longer drug-survival than 6-MP (Mantel-Cox rank test: <i>p</i> = 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 (<i>p</i> = 0.022). The median 6-thioguanine nucleotide levels in patients treated with thioguanine was 364 pmol/8 × 10<sup>8</sup>. 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 <i>versus</i> 109 µg/g; <i>p</i> = 0.023), but there was no significant difference in FC levels for thioguanine compared to azathioprine (50 <i>versus</i> 109 µg/g; <i>p</i> = 0.33).</p><p><strong>Conclusion: </strong>Treatment with a low dose of thioguanine is well-tolerated in patients with IBD and had a significantly higher drug-survival than conventional thiopurines.</p>\",\"PeriodicalId\":48770,\"journal\":{\"name\":\"Therapeutic Advances in Gastroenterology\",\"volume\":\"17 \",\"pages\":\"17562848241228064\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-02-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880529/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562848241228064\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562848241228064","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
The drug-survival of low-dose thioguanine in patients with inflammatory bowel disease: a retrospective observational study.
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.
期刊介绍:
Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area.
The editors welcome original research articles across all areas of gastroenterology and hepatology.
The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.