Association between 6-thioguanine nucleotide levels and preventing production of antibodies to infliximab in patients with inflammatory bowel disease.

IF 3.3 Q2 GASTROENTEROLOGY & HEPATOLOGY BMJ Open Gastroenterology Pub Date : 2023-06-01 DOI:10.1136/bmjgast-2023-001149

Jennifer Phillips, Sam Leary, Jonathan Tyrrell-Price

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Abstract

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.

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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

目的:英夫利昔单抗和硫嘌呤联合治疗炎症性肠病(IBD)患者已被证明比单药治疗更有效。硫嘌呤的治疗效果与6-硫鸟嘌呤(6-TGN)水平在235 ~ 450 pmol/8×108红细胞之间相关。该研究的主要目的是研究6-TGN水平与抑制预防英夫利昔单抗(ATI)抗体产生之间的关系。设计:我们对布里斯托大学医院NHS基金会信托接受英夫利昔单抗治疗IBD患者的医疗记录进行了回顾性审查。提取了人口统计学和生化数据，以及硫嘌呤代谢物水平、英夫利昔单抗低谷水平和ATI的存在。采用χ2检验探讨6-TGN水平与ATI预防之间的关系。采用Logistic回归比较6-TGN水平在235 - 450 pmol/8×108之间的红细胞、6-TGN水平在此范围之外的红细胞和接受英夫利昔单抗单药治疗的基线组预防ATI的几率。结果:共提取100例患者资料。32例6-TGN水平在235 - 450 pmol/8×108之间的患者中有6例发生ATI(18.8%)，而22例6-TGN水平不在此范围内的患者中有14例(63.6%)，46例单药治疗患者中有32例(69.6%)(p=0.001)。6-TGN在235 - 450 pmol/8×108之间的患者与6-TGN不在此范围内的患者相比，ATI预防的OR (95% CI)为7.6 (2.2,26.3)(p=0.001)，与单药治疗相比为9.9 (3.3,29.4)(p=0.001)。结论:235 ~ 450 pmol/8×108红细胞6-TGN水平可抑制ATI的产生。这支持治疗药物监测，以帮助指导治疗，并最大限度地提高IBD患者联合治疗的有益效果。

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来源期刊

BMJ Open Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

5.90

自引率

3.20%

发文量

审稿时长

2 weeks

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.