评估暴露于不同剂量肿瘤坏死因子抑制剂的免疫介导炎症性疾病中的癌症风险。
Estimating cancer risk in immune-mediated inflammatory diseases exposed to varying doses of tumour necrosis factor inhibitors.
作者信息
Okabayashi Shinji, Itaya Takahiro, Yamazaki Hajime, Yanai Ryo, Isshiki Masaaki, Yamamoto Yosuke
机构信息
Department of Healthcare Epidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Syogoin, Sakyo-ku, Kyoto-shi, Kyoto, 606-8507, Japan.
出版信息
J Gastroenterol. 2025 Mar;60(3):285-293. doi: 10.1007/s00535-024-02190-z. Epub 2024 Dec 5.
BACKGROUND
The safety profile of high doses of tumour necrosis factor inhibitors (TNFi) therapy for cancer risk in immune-mediated inflammatory diseases (IMIDs) remains uncertain. We evaluated the risk of cancer development in patients with IMIDs exposed to standard and high doses of TNFi compared with those never exposed to TNFi.
METHODS
A cohort study was conducted using the Japanese claims database encompassing over 4.6 million individuals from 2013 to 2021. The study included patients aged 16 years or older with new-onset IMIDs, such as inflammatory bowel disease, rheumatoid arthritis, or psoriasis, who had no cancer history. The subdistribution hazard ratios (SHR) for cancer risk in TNFi standard and high dose groups comparing with TNFi unexposed group were estimated using a Fine and Gray model that accounted for the competing risk of death unrelated to cancer. The high dose of TNFi was defined as either a dose escalation or shortening of the intervals during administrations from the standard dose treatment.
RESULTS
We identified a total of 42,006 patients with new-onset IMIDs (40,573 in TNFi unexposed, 876 in TNFi standard dose, and 557 in TNFi high dose) and 1211 (2.8%) patients developed cancer, yielding an incidence rate of 787.8 (739.9-828.1) per 100,000 person-years. Neither the standard nor high doses of TNFi significantly increased the cancer risk (TNFi standard dose vs. TNFi unexposed, adjusted SHR, 0.65 [0.40-1.08]; TNF high dose vs. TNFi unexposed, adjusted SHR, 1.12 [0.67-1.87]).
CONCLUSIONS
There is no association between varying doses of TNFi therapy and cancer risk in IMIDs.
背景
高剂量肿瘤坏死因子抑制剂（TNFi）治疗免疫介导的炎症性疾病（IMIDs）时癌症风险的安全性尚不确定。我们评估了暴露于标准剂量和高剂量TNFi的IMIDs患者与未暴露于TNFi的患者相比发生癌症的风险。
方法
使用日本索赔数据库进行队列研究，该数据库涵盖了2013年至2021年的460多万人。研究纳入了16岁及以上新发性IMIDs患者，如炎症性肠病、类风湿性关节炎或银屑病，且无癌症病史。使用考虑了与癌症无关的死亡竞争风险的Fine和Gray模型，估计TNFi标准剂量组和高剂量组与未暴露于TNFi组相比癌症风险的亚分布风险比（SHR）。高剂量TNFi定义为与标准剂量治疗相比给药期间剂量增加或间隔缩短。
结果
我们共识别出42006例新发性IMIDs患者（未暴露于TNFi组40573例，TNFi标准剂量组876例，TNFi高剂量组557例），其中1211例（2.8%）发生癌症，发病率为每10万人年787.8（739.9 - 828.1）例。TNFi的标准剂量和高剂量均未显著增加癌症风险（TNFi标准剂量组与未暴露于TNFi组相比，调整后的SHR为0.65 [0.40 - 1.08]；TNFi高剂量组与未暴露于TNFi组相比，调整后的SHR为1.12 [0.67 - 1.87]）。
结论
不同剂量的TNFi治疗与IMIDs患者的癌症风险之间无关联。
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