Qiao Qian, Sun Jiachen, Zheng Ya, Mi Yingying, Gong Yanan, Liu Jiahui, Rui Wenyue, Ma Yumei, Zhou Yongning, Liu Min
The First Clinical Medical College, Lanzhou University, Lanzhou, China.
Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.
Front Pharmacol. 2025 Jan 8;15:1507196. doi: 10.3389/fphar.2024.1507196. eCollection 2024.
This study aimed to evaluate the risk of tumor formation with infliximab or azathioprine monotherapy versus their combination, using the FDA Adverse Event Reporting System (FAERS) database.
Data were extracted from the FAERS database for patients treated with infliximab, azathioprine, and combination therapy from Q1 2004 to Q2 2024. Signal mining employed methods such as Reported Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multiple Gamma-Poisson Scaling Assessment (MGPSA) and Bayesian Confidence Interval Progressive Neural Network (BCPNN).
Our analysis of the FAERS database revealed that the highest number of reported cases involved skin-related tumors, both individually and in combination. In terms of sex, the risk of cancer was higher in men compared to women in the infliximab-only and combination groups; however, no sex difference was observed in the azathioprine-only group. Regarding age, we noted an increasing incidence of adverse tumor events in middle-aged and elderly individuals compared to minors, except in the azathioprine group, where age was not identified as an independent risk factor. Additionally, body weight was not found to be an independent risk factor in any of the three medication groups. After controlling for age, sex, and body weight, combination therapy did not increase the risk of tumor development compared to the azathioprine group alone. In contrast, for patients using infliximab alone, combination therapy not only did not elevate the risk of tumor development but also appeared to reduce it. The results of the Weber distribution suggest a random failure-type profile for the infliximab and azathioprine-only group, while an early failure-type profile was observed for the combination therapy. Furthermore, we analyzed the median time to onset and cumulative incidence rates, revealing no significant differences in median time to tumor onset or cumulative incidence rates between the combination therapy and the single agent.
After adjusting for age, sex, and body weight, combination therapy did not significantly increase tumor development risk compared to the azathioprine-only group. Additionally, in patients on infliximab monotherapy, combination therapy appeared to reduce the risk of tumor development.
本研究旨在利用美国食品药品监督管理局不良事件报告系统（FAERS）数据库，评估英夫利昔单抗或硫唑嘌呤单药治疗与联合治疗的肿瘤形成风险。
从FAERS数据库中提取2004年第一季度至2024年第二季度接受英夫利昔单抗、硫唑嘌呤及联合治疗患者的数据。信号挖掘采用报告比值比（ROR）、比例报告比（PRR）、多重伽马-泊松标度评估（MGPSA）和贝叶斯置信区间渐进神经网络（BCPNN）等方法。
我们对FAERS数据库的分析显示，报告病例数最多的是与皮肤相关的肿瘤，无论是单药治疗还是联合治疗。在性别方面，仅使用英夫利昔单抗组和联合治疗组中男性患癌风险高于女性；然而，仅使用硫唑嘌呤组未观察到性别差异。在年龄方面，我们注意到与未成年人相比，中年和老年个体不良肿瘤事件的发生率有所增加，但硫唑嘌呤组除外，在该组中年龄未被确定为独立风险因素。此外，在三个用药组中，体重均未被发现是独立风险因素。在控制年龄、性别和体重后，与单独使用硫唑嘌呤组相比，联合治疗并未增加肿瘤发生风险。相比之下，对于仅使用英夫利昔单抗的患者，联合治疗不仅没有增加肿瘤发生风险，反而似乎降低了风险。韦伯分布结果表明，仅使用英夫利昔单抗和硫唑嘌呤组呈随机失效型分布，而联合治疗观察到早期失效型分布。此外，我们分析了发病中位时间和累积发病率，结果显示联合治疗与单药治疗在肿瘤发病中位时间或累积发病率方面无显著差异。
在调整年龄、性别和体重后，与仅使用硫唑嘌呤组相比，联合治疗并未显著增加肿瘤发生风险。此外，对于接受英夫利昔单抗单药治疗的患者，联合治疗似乎降低了肿瘤发生风险。
