初治或接受硫嘌呤及靶向治疗的溃疡性结肠炎患者的癌症发病率——一项2007年至2022年的队列研究，并与普通人群进行比较
Cancer incidence in patients with ulcerative colitis naïve to or treated with thiopurine and targeted therapies-a cohort study 2007 to 2022 with comparison to the general population.
作者信息
Everhov Åsa H, Askling Johan, Söderling Jonas, Halfvarson Jonas, Eriksson Julia, Smedby Karin E, Ludvigsson Jonas F, Sørensen Henrik Toft, Olén Ola
机构信息
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
出版信息
J Crohns Colitis. 2025 Jun 4;19(6). doi: 10.1093/ecco-jcc/jjaf091.
BACKGROUND
Cancer incidence data including absolute risk differences are needed for clinical risk communication to patients receiving modern-day treatments for ulcerative colitis (UC).
METHODS
We linked nationwide Swedish health registers and assessed incident cancers in patients with UC in 2007-2022. We computed age-stratified incidence rates (IRs), IR differences, and hazard ratios (HRs) in a naïve cohort with no immunomodulatory treatment, and in cohorts treated with thiopurine or targeted therapies. General population comparator subjects were matched (by age, sex, calendar year, and area of residence) to each treatment cohort. We used a once-exposed-always-exposed design.
RESULTS
We identified 63 925 patients with UC in partly overlapping cohorts and 593 072 comparators with a total follow-up time of 5 800 089 years (median 8.1 years). The IRs were elevated compared to the general population in naïve patients: 2.7 extra cancer cases per 1000 person-years (HR: 1.12, 95% CI, 1.09-1.16), in thiopurine-treated patients: 3.4 extra cases (HR: 1.48;1.37-1.61), tumor necrosis factor inhibitor (TNFi)-treated: 2.7 extra cases (HR: 1.41;1.24-1.62), Thiopurine + TNFi-treated: 2.42 extra cases (HR: 1.44;1.19-1.75), vedolizumab-treated: 2.88 extra cases (HR: 1.27;0.90-1.79). The IR differences were not significantly increased in patients treated with ustekinumab 0.57 (HR: 0.87;0,39-1.93) and tofacitinib -0.69 (HR: 0.84;0.25-2.77). Across all treatment groups, the IR differences compared to the general population were highest in patients ≥ 60 years. The differences were driven by colorectal cancer, hepatobiliary cancer, lymphoma, and basal cell skin carcinoma.
CONCLUSIONS
Elevated cancer incidence was observed in patients with UC amounting to around 3 extra cases of cancer per 1000 years. Cancer risks varied more among groups defined by age than by treatment.
背景
对于接受现代溃疡性结肠炎（UC）治疗的患者进行临床风险沟通，需要包括绝对风险差异在内的癌症发病率数据。
方法
我们将瑞典全国范围内的健康登记数据相链接，并评估了2007年至2022年期间UC患者的新发癌症情况。我们计算了未接受免疫调节治疗的单纯队列、接受硫唑嘌呤或靶向治疗的队列中按年龄分层的发病率（IRs）、IR差异和风险比（HRs）。将一般人群对照对象（按年龄、性别、日历年和居住地区）与每个治疗队列进行匹配。我们采用一次暴露即始终暴露的设计。
结果
我们在部分重叠的队列中识别出63925例UC患者和593072例对照对象，总随访时间为5800089年（中位数8.1年）。与一般人群相比，未接受治疗的患者IRs升高：每1000人年额外有2.7例癌症病例（HR：1.12，95%CI，1.09 - 1.16），接受硫唑嘌呤治疗的患者：额外3.4例（HR：1.48；1.37 - 1.61），接受肿瘤坏死因子抑制剂（TNFi）治疗的患者：额外2.7例（HR：1.41；1.24 - 1.62），接受硫唑嘌呤 + TNFi治疗的患者：额外2.42例（HR：1.44；1.19 - 1.75），接受维多珠单抗治疗患者：额外2.88例（HR：1.27；0.90 - 1.79）。接受乌司奴单抗治疗的患者IR差异未显著增加，为0.57（HR：0.87；0.39 - 1.93），接受托法替布治疗的患者为 - 0.69（HR：0.84；0.25 - 2.77）。在所有治疗组中，与一般人群相比，IR差异在≥60岁的患者中最高。差异由结直肠癌、肝胆癌、淋巴瘤和基底细胞皮肤癌导致。
结论
观察到UC患者癌症发病率升高，每1000年约额外有3例癌症病例。癌症风险在按年龄定义的组间差异比按治疗定义的组间差异更大。
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