Wewer Mads Damsgaard, Letnar Gasper, Andersen Klaus Kaae, Malham Mikkel, Wewer Vibeke, Seidelin Jakob Benedict, Bendtsen Flemming, Burisch Johan
Gastro Unit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark; Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark.
Omicron ApS, Copenhagen, Denmark.
Clin Gastroenterol Hepatol. 2025 May;23(6):1030-1038. doi: 10.1016/j.cgh.2024.08.006. Epub 2024 Aug 28.
BACKGROUND & AIMS: Thiopurine therapy is a cornerstone in the treatment of inflammatory bowel disease (IBD). We aimed to assess the effect of thiopurines on cancer risk in IBD according to drug exposure and age.
Danish national registers were used to identify incident IBD patients, exposure to drugs, and status of cancers, in 1996 to 2018. Cox regressions were used to compare cancer risks in IBD and non-IBD individuals and to assess IBD patients' cumulative drug exposure and the association to first cancer, excluding non-melanoma skin cancer.
We followed 43,419 patients with IBD for a median of 8.2 years (interquartile range, 3.7-14.2 years) after IBD diagnosis. Cancer was reported in 3128 (7.2%) patients with IBD. The risk of cancer was increased in patients with IBD in all age categories compared with non-IBD individuals (<50 years: adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.43-1.77; 50-65 years: aHR, 1.31; 95% CI, 1.19-1.44; and >65 years: aHR, 1.14; 95% CI, 1.05-1.24). Monotherapy (aHR, 1.36; 95% CI, 1.17-1.57) and combination therapy (aHR, 2.49; 95% CI, 1.64-3.78) were associated with an increased risk of cancer compared to unexposed patients with IBD. Among elderly patients (>65 years), the aHR was 2.79 (95% CI, 1.24-6.28) in those receiving combination therapy. In patients discontinuing thiopurines, aHRs returned to the level of unexposed (aHR, 0.89; 95% CI, 0.78-1.01). The aHR was positively associated with cumulative thiopurine exposure and in patients with >5 years of exposure, reaching an aHR of 1.36 (95% CI, 1.15-1.61).
Thiopurines were associated with increased hazard of cancer, especially when used in combination therapy in the elderly. The hazard increased by 36% when patients were exposed to thiopurines for more than 5 years. Reassuringly, the hazard returned to baseline after discontinuation of thiopurines.
硫嘌呤类药物治疗是炎症性肠病（IBD）治疗的基石。我们旨在根据药物暴露情况和年龄评估硫嘌呤类药物对IBD患者癌症风险的影响。
利用丹麦国家登记系统确定1996年至2018年期间的IBD确诊患者、药物暴露情况及癌症状态。采用Cox回归比较IBD患者和非IBD个体的癌症风险，并评估IBD患者的累积药物暴露情况及其与首次发生癌症（不包括非黑色素瘤皮肤癌）的关联。
在IBD确诊后，我们对43419例IBD患者进行了中位时间为8.2年（四分位间距为3.7 - 14.2年）的随访。3128例（7.2%）IBD患者报告患癌。与非IBD个体相比，各年龄组IBD患者的癌症风险均增加（<50岁：调整后风险比[aHR]为1.59；95%置信区间[CI]为1.43 - 1.77；50 - 65岁：aHR为1.31；95% CI为1.19 - 1.44；>65岁：aHR为1.14；95% CI为1.05 - 1.24）。与未暴露于硫嘌呤类药物的IBD患者相比，单药治疗（aHR为1.36；95% CI为1.17 - 1.57）和联合治疗（aHR为2.49；95% CI为1.64 - 3.78）与癌症风险增加相关。在老年患者（>65岁）中，接受联合治疗的患者aHR为2.79（95% CI为1.24 - 6.28）。在停用硫嘌呤类药物的患者中，aHR恢复到未暴露患者的水平（aHR为0.89；95% CI为0.78 - 1.01）。aHR与硫嘌呤类药物的累积暴露呈正相关，在暴露超过5年的患者中，aHR达到1.36（95% CI为1.15 - 1.61）。
硫嘌呤类药物与癌症风险增加相关，尤其是在老年患者中联合使用时。患者暴露于硫嘌呤类药物超过5年时，风险增加36%。令人安心的是，停用硫嘌呤类药物后风险恢复到基线水平。
