背景:最近,由于光化性角化病(AK)患者的鳞状细胞癌(SCC)的风险可能增加,因此在欧盟(EU)和加拿大停止了丁烯二酚的生产和销售。
目的:在FDA不良事件报告系统(FAERS)中,探讨SCC与局部AK药物(包括甲辛酯)之间的关系。
方法:使用2012年至2020年的数据在FAERS中进行了病例/非病例分析,以检查在多种情况下,辛伐他汀醇和所有类别的局部AK药物的SCC的报告优势比(ROR)信号:i.与FAER中的所有其他药物进行比较,Iftheparticularstandardsoftheparticularly,theparticularlytotheparticularlyofthebetweenthepurpose.与其他局部AK药物相比,与所有其他仅涉及单一药物的局部AK药物相比,Ifthepurchasesofthepurposaloftheparticular.丁烯酚与甲磺酸酯的比较咪喹莫特.
结果:在所有条件下,辛烷醇都发现SCC的ROR具有统计学意义(i。31.57(25.45,39.16),Iftheparticularstandardsoftheparticularly,theparticularlytotheparticularlyofthebetweenthepurpose.50.35(32.21,78.82),iii61.09(35.36,105.56),Ifthepurchasesofthepurposaloftheparticular.2.53(1.27,5.05)。对于咪喹莫特(i。12.38(6.42,32.84),Iftheparticularstandardsoftheparticularly,theparticularlytotheparticularlyofthebetweenthepurpose.5.18(2.61,10.26),三5.42(2.49,11.78),但不是氟尿嘧啶或双氯芬酸。当直接与咪喹莫特相比时,辛烷醇对SCC的ROR具有统计学意义(2.53(1.27,5.05)。
结论:我们的研究结果支持SCC与甲骨酚之间的关联。这种关联在控制下保持,以限制偏倚和错误升高的信号,包括控制疾病状态和多种药物暴露的病例,以及与甲磺酸酯IV期研究中的咪喹莫特相比。
BACKGROUND: Recently the production and marketing of ingenol mebutate in the European Union (EU) and Canada was halted due to a possible increased risk of squamous cell carcinoma (SCC) in patients with actinic keratosis (AK).
OBJECTIVE: To investigate the relationship between SCC and topical AK medications including ingenol mebutate in the FDA Adverse Event Reporting System (FAERS).
METHODS: Case/non-case analyses were performed in FAERS using data from 2012 to 2020 to examine the reporting odds ratio (ROR) signal for SCC for ingenol mebutate and all classes of topical AK medications under multiple conditions: i. comparison to all other drugs in FAERs, ii. comparison to other topical AK medications, iii. comparison to all other topical AK medications where only a single agent was implicated, iv. comparison of ingenol mebutate vs. imiquimod.
RESULTS: A statistically significant ROR for SCC was found for ingenol mebutate under all conditions (i. 31.57 (25.45, 39.16), ii. 50.35 (32.21, 78.82), iii 61.09 (35.36, 105.56), iv. 2.53 (1.27, 5.05). A significant but substantially smaller signal was observed for imiquimod (i. 12.38 (6.42, 32.84), ii. 5.18 (2.61, 10.26), iii 5.42 (2.49, 11.78), but not for fluorouracil or diclofenac. When compared to imiquimod directly, ingenol mebutate had a statistically significant ROR for SCC (2.53 (1.27, 5.05).
CONCLUSIONS: Our findings support an association between SCC and ingenol mebutate. This association is maintained under controls to limit bias and falsely elevated signal including controlling for disease state and cases with multiple drug exposures and when compared to imiquimod as in Phase IV studies of ingenol mebutate.