■硫嘌呤通常用于治疗炎症性肠病,但由于副作用而戒断是常见的。已经提出硫鸟嘌呤比常规硫嘌呤具有更好的耐受性。
■我们在现实生活中的临床实践中研究了低剂量硫鸟嘌呤与常规硫嘌呤的药物存活率。
■回顾性观察性研究。
■所有1956年及以后出生的患者,纳入了2006年至2022年期间至少一次开始硫嘌呤治疗的患者.进行了医学图表审查,记录了每次硫嘌呤治疗尝试的药物存活率。Mantel-Cox秩检验用于测试不同硫嘌呤的药物存活率差异。在治疗的前5年记录血液化学分析和粪便钙卫蛋白水平。
■在研究人群中,在307例炎症性肠病(IBD)患者中,有379例开始硫嘌呤治疗(克罗恩病210例,溃疡性结肠炎169例).31例患者开始使用低剂量硫鸟嘌呤(中位剂量11mg;25-75百分位数7-19mg)。总的来说,当包括所有硫嘌呤尝试时,硫鸟嘌呤的药物生存期最长[Mantel-Cox秩检验:硫鸟嘌呤与硫唑嘌呤p=0.014;硫鸟嘌呤与6-巯基嘌呤(6-MP)p<0.001]。对于二线硫嘌呤治疗,硫鸟嘌呤比6-MP具有更长的药物生存期(Mantel-Cox秩检验:p=0.006)。60个月时,86%开始低剂量硫鸟嘌呤的患者仍在接受治疗,而42%开始6-MP的患者仍在接受治疗(p=0.022)。用硫鸟嘌呤治疗的患者的6-硫鸟嘌呤核苷酸水平中位数为364pmol/8×108。与硫唑嘌呤和6-MP治疗的患者相比,接受硫鸟嘌呤治疗的患者在随访时显示出的平均红细胞体积中位数值显着降低。与使用硫唑嘌呤治疗的患者相比,使用6-MP治疗的患者在治疗的第三年表现出明显较低的FC水平(59对109µg/g;p=0.023),但与硫唑嘌呤相比,硫代鸟嘌呤的FC水平没有显着差异(50对109µg/g;p=0.33)。
■低剂量硫鸟嘌呤治疗IBD患者耐受性良好,药物存活率明显高于常规硫嘌呤。
炎症性肠病患者对低剂量的免疫调节剂药物硫鸟嘌呤具有良好的耐受性。硫鸟嘌呤通常用于治疗炎症性肠病,但通常患者由于副作用而终止治疗。硫嘌呤硫鸟嘌呤被认为比其他硫嘌呤具有更好的耐受性。我们的目的是研究在我们的临床中,在炎症性肠病患者中,低剂量的硫鸟嘌呤是否比其他硫嘌呤耐受性更好,使用时间更长。在研究人群中,在307例炎症性肠病患者中,有379例开始了硫代嘌呤治疗。在这些患者中,31名患者开始使用低剂量硫鸟嘌呤。总的来说,当包括所有硫嘌呤尝试时,硫鸟嘌呤在所有硫嘌呤中的药物生存期最长。对于二线硫嘌呤治疗,硫鸟嘌呤比通常用作二线硫嘌呤治疗的硫嘌呤6-巯基嘌呤具有更长的药物存活率。60个月时,86%开始低剂量硫鸟嘌呤的患者仍在接受治疗,而42%开始6-巯基嘌呤的患者仍在接受治疗。与常规使用的硫嘌呤相比,在开始使用硫胍治疗的前五年,对炎症标志物的反应相似。我们得出的结论是,在炎症性肠病患者中,低剂量的硫鸟嘌呤治疗具有良好的耐受性,并且与常规的硫嘌呤相比,药物存活率显着提高。
UNASSIGNED: 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.
UNASSIGNED: We studied drug-survival of low dose of thioguanine in real-life clinical practice in comparison to conventional thiopurines.
UNASSIGNED: Retrospective observational study.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.