磷酸二酯酶-5抑制剂相关黑色素瘤不良反应2161例

2161 Cases of Adverse Reactions of Melanoma Associated with Phosphodiesterase-5 Inhibitors

目的:探索磷酸二酯酶-5(PDE-5)抑制剂与黑色素瘤的关系。方法:检索2004年1月至2021年3月美国食品药品监督管理局的不良事件报告系统(FAERS),使用比值失衡测量法和贝叶斯法对PDE-5抑制剂使用后黑色素瘤可疑不良事件进行数据挖掘。对不同PDE-5抑制剂相关黑色素瘤发病时间及致死率进行分析比较。结果:PDE-5抑制剂相关黑色素瘤不良反应个案总共2 161例。在6种PDE-5抑制剂中,根据最高的报告优势比(ROR=43.57,95%双侧可信区间=40.61~46.75)、比例报告优势比(PRR=41.92,χ^(2)=32 138.14)和经验贝叶斯几何平均值(EBGM=39.24,95%单侧可信区间=37.00),他达那非与黑色素瘤的相关性最高。与西地那非相比较,服用他达那非出现黑色素瘤的时间更早[1 318(IQR 629~2 352)d vs 1 732(IQR 867~3 121)d,P<0.01]。但他达那非相关黑色素瘤病死率更低(7.31% vs 8.1%,P<0.01)。结论:PDE-5抑制剂会增加罹患黑色素瘤的风险;与西地那非相比较,服用他达那非与黑色素瘤的相关性高。

Objectives:To explore the relationship between phosphodiesterase-5(PDE-5)inhibitors use and melanoma.Methods:Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected adverse events of melanoma after PDE-5 inhibitors use based on the Food and Drug Administration's Adverse Event Reporting System(FAERS)from January 2004 to March 2021.The times to onset and fatality rate of melanom following different PDE-5 inhibitors were also compared.Results:A total of 2161 cases of melanoma adverse events were reported with PDE-5 inhibitors.Among 6 PDE-5 inhibitors,tadalafil had the highest association with melanoma based on the highest reporting odds ratio(ROR=43.57,95%two-sided CI=40.61–46.75),proportional reporting ratio(PRR=41.92,χ^(2)=32138.14)and empirical bayes geometric mean(EBGM=39.24,95%one-sided CI=37.00).Melanoma associated with tadalafil treatment appeared to have earlier onset[1318(IQR 620-2353)vs 1732(IQR 867-3121),P<0.01],but lower fatality rate(7.31%vs 8.18%,P<0.01)than that associated with sildenafil.Conclusions:PDE-5 inhibitors increase the risk of melanoma;tardenafil administration have the higer association with melanoma when compared to sildenafil.