Jennifer Phillips, Sam Leary, Jonathan Tyrrell-Price
{"title":"炎症性肠病患者6-硫鸟嘌呤核苷酸水平与预防英夫利昔单抗抗体产生之间的关系","authors":"Jennifer Phillips, Sam Leary, Jonathan Tyrrell-Price","doi":"10.1136/bmjgast-2023-001149","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Combination therapy with infliximab and a thiopurine has been shown to be more effective than monotherapy in patients with inflammatory bowel disease (IBD). The therapeutic efficacy of thiopurines is correlated with 6-thioguanine (6-TGN) levels between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes. The primary aim of the study was to investigate the association between 6-TGN levels and inhibition prevention of the production of antibodies to infliximab (ATI).</p><p><strong>Design: </strong>We performed a retrospective review of the medical records of patients being treated with infliximab for IBD at University Hospitals Bristol NHS Foundation Trust. Demographic and biochemical data were extracted, alongside thiopurine metabolite levels, trough levels of infliximab and the presence of ATI. χ<sup>2</sup> tests were used to investigate the association between 6-TGN levels and prevention of ATI. Logistic regression was used to compare the odds of prevented ATI between those with a 6-TGN level between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes, those with a 6-TGN level outside of this range, and the baseline group who were on infliximab monotherapy.</p><p><strong>Results: </strong>Data were extracted for 100 patients. Six of 32 patients with a 6-TGN level between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes developed ATI (18.8%) compared with 14 out of 22 (63.6%) patients with a 6-TGN outside of this range and 32 out of 46 (69.6%) patients on monotherapy (p=0.001). The OR (95% CI) for prevented ATI in those with a 6-TGN between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes compared with a 6-TGN outside of this range was 7.6 (2.2, 26.3) (p=0.001) and compared with monotherapy was 9.9 (3.3, 29.4) (p=0.001).</p><p><strong>Conclusion: </strong>6-TGN levels between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes prevented production of ATI. This supports therapeutic drug monitoring to help guide treatment and maximise the beneficial effects of combination therapy for patients with IBD.</p>","PeriodicalId":9235,"journal":{"name":"BMJ Open Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/3e/bmjgast-2023-001149.PMC10277032.pdf","citationCount":"0","resultStr":"{\"title\":\"Association between 6-thioguanine nucleotide levels and preventing production of antibodies to infliximab in patients with inflammatory bowel disease.\",\"authors\":\"Jennifer Phillips, Sam Leary, Jonathan Tyrrell-Price\",\"doi\":\"10.1136/bmjgast-2023-001149\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Combination therapy with infliximab and a thiopurine has been shown to be more effective than monotherapy in patients with inflammatory bowel disease (IBD). The therapeutic efficacy of thiopurines is correlated with 6-thioguanine (6-TGN) levels between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes. The primary aim of the study was to investigate the association between 6-TGN levels and inhibition prevention of the production of antibodies to infliximab (ATI).</p><p><strong>Design: </strong>We performed a retrospective review of the medical records of patients being treated with infliximab for IBD at University Hospitals Bristol NHS Foundation Trust. Demographic and biochemical data were extracted, alongside thiopurine metabolite levels, trough levels of infliximab and the presence of ATI. χ<sup>2</sup> tests were used to investigate the association between 6-TGN levels and prevention of ATI. Logistic regression was used to compare the odds of prevented ATI between those with a 6-TGN level between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes, those with a 6-TGN level outside of this range, and the baseline group who were on infliximab monotherapy.</p><p><strong>Results: </strong>Data were extracted for 100 patients. Six of 32 patients with a 6-TGN level between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes developed ATI (18.8%) compared with 14 out of 22 (63.6%) patients with a 6-TGN outside of this range and 32 out of 46 (69.6%) patients on monotherapy (p=0.001). The OR (95% CI) for prevented ATI in those with a 6-TGN between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes compared with a 6-TGN outside of this range was 7.6 (2.2, 26.3) (p=0.001) and compared with monotherapy was 9.9 (3.3, 29.4) (p=0.001).</p><p><strong>Conclusion: </strong>6-TGN levels between 235 and 450 pmol/8×10<sup>8</sup> erythrocytes prevented production of ATI. This supports therapeutic drug monitoring to help guide treatment and maximise the beneficial effects of combination therapy for patients with IBD.</p>\",\"PeriodicalId\":9235,\"journal\":{\"name\":\"BMJ Open Gastroenterology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/3e/bmjgast-2023-001149.PMC10277032.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMJ Open Gastroenterology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1136/bmjgast-2023-001149\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Gastroenterology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1136/bmjgast-2023-001149","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Association between 6-thioguanine nucleotide levels and preventing production of antibodies to infliximab in patients with inflammatory bowel disease.
Objective: Combination therapy with infliximab and a thiopurine has been shown to be more effective than monotherapy in patients with inflammatory bowel disease (IBD). The therapeutic efficacy of thiopurines is correlated with 6-thioguanine (6-TGN) levels between 235 and 450 pmol/8×108 erythrocytes. The primary aim of the study was to investigate the association between 6-TGN levels and inhibition prevention of the production of antibodies to infliximab (ATI).
Design: We performed a retrospective review of the medical records of patients being treated with infliximab for IBD at University Hospitals Bristol NHS Foundation Trust. Demographic and biochemical data were extracted, alongside thiopurine metabolite levels, trough levels of infliximab and the presence of ATI. χ2 tests were used to investigate the association between 6-TGN levels and prevention of ATI. Logistic regression was used to compare the odds of prevented ATI between those with a 6-TGN level between 235 and 450 pmol/8×108 erythrocytes, those with a 6-TGN level outside of this range, and the baseline group who were on infliximab monotherapy.
Results: Data were extracted for 100 patients. Six of 32 patients with a 6-TGN level between 235 and 450 pmol/8×108 erythrocytes developed ATI (18.8%) compared with 14 out of 22 (63.6%) patients with a 6-TGN outside of this range and 32 out of 46 (69.6%) patients on monotherapy (p=0.001). The OR (95% CI) for prevented ATI in those with a 6-TGN between 235 and 450 pmol/8×108 erythrocytes compared with a 6-TGN outside of this range was 7.6 (2.2, 26.3) (p=0.001) and compared with monotherapy was 9.9 (3.3, 29.4) (p=0.001).
Conclusion: 6-TGN levels between 235 and 450 pmol/8×108 erythrocytes prevented production of ATI. This supports therapeutic drug monitoring to help guide treatment and maximise the beneficial effects of combination therapy for patients with IBD.
期刊介绍：
BMJ Open Gastroenterology is an online-only, peer-reviewed, open access gastroenterology journal, dedicated to publishing high-quality medical research from all disciplines and therapeutic areas of gastroenterology. It is the open access companion journal of Gut and is co-owned by the British Society of Gastroenterology. The journal publishes all research study types, from study protocols to phase I trials to meta-analyses, including small or specialist studies. Publishing procedures are built around continuous publication, publishing research online as soon as the article is ready.
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