{"title":"丝裂霉素的真实安全概况:来自FDA不良事件报告系统和VigiAccess数据库的信号检测和发病时间分析","authors":"Zhenghua Hao, Linglu Yu","doi":"10.1007/s11096-025-01994-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Mitomycin, a cytotoxic antitumor antibiotic, has been approved for the treatment of low-grade upper tract urothelial carcinoma (UTUC) and non-muscle invasive bladder cancer (NMIBC). It is also used off-label in ophthalmic procedures and gastrointestinal malignancies. Although the efficacy of mitomycin is well recognized, its safety profile, particularly regarding rare or serious adverse events (AEs), remains insufficiently characterized in large real-world populations.</p><p><strong>Aim: </strong>This study aimed to evaluate mitomycin-associated AEs through comprehensive analysis of two major global pharmacovigilance databases, with the goal of identifying high-risk organ systems and specific AE signals requiring increased clinical awareness.</p><p><strong>Method: </strong>AE data were retrieved from the FDA Adverse Event Reporting System (FAERS) covering Q1 2004 to Q3 2024. Data were deduplicated and standardized according to MedDRA terminology. Complementary data were collected from the World Health Organization VigiAccess database. Disproportionality analysis was performed using four signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The time-to-onset of adverse events was analyzed using non-parametric statistical methods.</p><p><strong>Results: </strong>A total of 1461 mitomycin-related reports, comprising 3652 AEs, were identified in the FAERS database. Notably, strong safety signals have emerged at the system organ class (SOC) level for eye, renal and urinary, blood and lymphatic system, and skin and subcutaneous tissue disorders. At the preferred term (PT) level, high disproportionality values were observed for serious events, such as scleral thinning (OR = 7129.60, 95% CI 4576.64-11,106.7) and bladder perforation (OR = 1585.69, 95% CI 1111.91-2261.33). Over two-thirds of AEs occurred within 30 days of drug administration, although 68.93% of the reports lacked valid onset-time data. The VigiAccess findings corroborated the SOC trends observed in FAERS.</p><p><strong>Conclusion: </strong>Mitomycin is associated with a broad range of organ-specific toxicities, many of which occur early in the treatment course and may have serious clinical consequences. This study highlights the need for early risk identification, individualized monitoring strategies, and greater pharmacovigilance in populations treated with mitomycin. These findings provide an important foundation for optimizing the safe and effective use of mitomycin in oncology and in other therapeutic settings.</p>","PeriodicalId":13828,"journal":{"name":"International Journal of Clinical Pharmacy","volume":" ","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Real-world safety profile of mitomycin: signal detection and time-to-onset analysis from FDA adverse event reporting system and VigiAccess databases.\",\"authors\":\"Zhenghua Hao, Linglu Yu\",\"doi\":\"10.1007/s11096-025-01994-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Mitomycin, a cytotoxic antitumor antibiotic, has been approved for the treatment of low-grade upper tract urothelial carcinoma (UTUC) and non-muscle invasive bladder cancer (NMIBC). It is also used off-label in ophthalmic procedures and gastrointestinal malignancies. Although the efficacy of mitomycin is well recognized, its safety profile, particularly regarding rare or serious adverse events (AEs), remains insufficiently characterized in large real-world populations.</p><p><strong>Aim: </strong>This study aimed to evaluate mitomycin-associated AEs through comprehensive analysis of two major global pharmacovigilance databases, with the goal of identifying high-risk organ systems and specific AE signals requiring increased clinical awareness.</p><p><strong>Method: </strong>AE data were retrieved from the FDA Adverse Event Reporting System (FAERS) covering Q1 2004 to Q3 2024. Data were deduplicated and standardized according to MedDRA terminology. Complementary data were collected from the World Health Organization VigiAccess database. Disproportionality analysis was performed using four signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The time-to-onset of adverse events was analyzed using non-parametric statistical methods.</p><p><strong>Results: </strong>A total of 1461 mitomycin-related reports, comprising 3652 AEs, were identified in the FAERS database. Notably, strong safety signals have emerged at the system organ class (SOC) level for eye, renal and urinary, blood and lymphatic system, and skin and subcutaneous tissue disorders. At the preferred term (PT) level, high disproportionality values were observed for serious events, such as scleral thinning (OR = 7129.60, 95% CI 4576.64-11,106.7) and bladder perforation (OR = 1585.69, 95% CI 1111.91-2261.33). Over two-thirds of AEs occurred within 30 days of drug administration, although 68.93% of the reports lacked valid onset-time data. The VigiAccess findings corroborated the SOC trends observed in FAERS.</p><p><strong>Conclusion: </strong>Mitomycin is associated with a broad range of organ-specific toxicities, many of which occur early in the treatment course and may have serious clinical consequences. This study highlights the need for early risk identification, individualized monitoring strategies, and greater pharmacovigilance in populations treated with mitomycin. 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引用次数: 0
摘要
丝裂霉素是一种细胞毒性抗肿瘤抗生素,已被批准用于治疗低级别上尿路上皮癌(UTUC)和非肌肉浸润性膀胱癌(NMIBC)。它也用于标签外眼科手术和胃肠道恶性肿瘤。尽管丝裂霉素的疗效得到了广泛的认可,但其安全性,特别是罕见或严重不良事件(ae),在现实世界的大量人群中仍未得到充分的表征。目的:本研究旨在通过对全球两个主要药物警戒数据库的综合分析,评估丝裂霉素相关AE,以识别高危器官系统和需要提高临床意识的特定AE信号。方法:从FDA不良事件报告系统(FAERS)检索2004年第一季度至2024年第三季度的AE数据。根据MedDRA术语对数据进行重复数据删除和标准化。补充数据从世界卫生组织VigiAccess数据库收集。歧化分析采用四种信号检测算法:报告比值比(ROR)、比例报告比(PRR)、贝叶斯置信传播神经网络(BCPNN)和多项目伽玛泊松收缩器(MGPS)。不良事件发生时间采用非参数统计方法进行分析。结果:FAERS数据库中共鉴定出1461例丝裂霉素相关报告,包括3652例ae。值得注意的是,在眼睛、肾脏和泌尿系统、血液和淋巴系统以及皮肤和皮下组织疾病的系统器官分类(SOC)水平上出现了强烈的安全信号。在首选项(PT)水平,高歧化值在严重事件中被观察到,如巩膜变薄(OR = 7129.60, 95% CI 4576.64-11,106.7)和膀胱穿孔(OR = 1585.69, 95% CI 1111.91-2261.33)。超过三分之二的ae发生在给药30天内,尽管68.93%的报告缺乏有效的发病时间数据。VigiAccess的研究结果证实了FAERS中观察到的SOC趋势。结论:丝裂霉素与广泛的器官特异性毒性相关,其中许多发生在治疗过程的早期,并可能产生严重的临床后果。这项研究强调了在接受丝裂霉素治疗的人群中需要进行早期风险识别、个性化监测策略和更大的药物警戒。这些发现为优化丝裂霉素在肿瘤和其他治疗环境中的安全有效使用提供了重要的基础。
Real-world safety profile of mitomycin: signal detection and time-to-onset analysis from FDA adverse event reporting system and VigiAccess databases.
Introduction: Mitomycin, a cytotoxic antitumor antibiotic, has been approved for the treatment of low-grade upper tract urothelial carcinoma (UTUC) and non-muscle invasive bladder cancer (NMIBC). It is also used off-label in ophthalmic procedures and gastrointestinal malignancies. Although the efficacy of mitomycin is well recognized, its safety profile, particularly regarding rare or serious adverse events (AEs), remains insufficiently characterized in large real-world populations.
Aim: This study aimed to evaluate mitomycin-associated AEs through comprehensive analysis of two major global pharmacovigilance databases, with the goal of identifying high-risk organ systems and specific AE signals requiring increased clinical awareness.
Method: AE data were retrieved from the FDA Adverse Event Reporting System (FAERS) covering Q1 2004 to Q3 2024. Data were deduplicated and standardized according to MedDRA terminology. Complementary data were collected from the World Health Organization VigiAccess database. Disproportionality analysis was performed using four signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The time-to-onset of adverse events was analyzed using non-parametric statistical methods.
Results: A total of 1461 mitomycin-related reports, comprising 3652 AEs, were identified in the FAERS database. Notably, strong safety signals have emerged at the system organ class (SOC) level for eye, renal and urinary, blood and lymphatic system, and skin and subcutaneous tissue disorders. At the preferred term (PT) level, high disproportionality values were observed for serious events, such as scleral thinning (OR = 7129.60, 95% CI 4576.64-11,106.7) and bladder perforation (OR = 1585.69, 95% CI 1111.91-2261.33). Over two-thirds of AEs occurred within 30 days of drug administration, although 68.93% of the reports lacked valid onset-time data. The VigiAccess findings corroborated the SOC trends observed in FAERS.
Conclusion: Mitomycin is associated with a broad range of organ-specific toxicities, many of which occur early in the treatment course and may have serious clinical consequences. This study highlights the need for early risk identification, individualized monitoring strategies, and greater pharmacovigilance in populations treated with mitomycin. These findings provide an important foundation for optimizing the safe and effective use of mitomycin in oncology and in other therapeutic settings.
期刊介绍:
The International Journal of Clinical Pharmacy (IJCP) offers a platform for articles on research in Clinical Pharmacy, Pharmaceutical Care and related practice-oriented subjects in the pharmaceutical sciences.
IJCP is a bi-monthly, international, peer-reviewed journal that publishes original research data, new ideas and discussions on pharmacotherapy and outcome research, clinical pharmacy, pharmacoepidemiology, pharmacoeconomics, the clinical use of medicines, medical devices and laboratory tests, information on medicines and medical devices information, pharmacy services research, medication management, other clinical aspects of pharmacy.
IJCP publishes original Research articles, Review articles , Short research reports, Commentaries, book reviews, and Letters to the Editor.
International Journal of Clinical Pharmacy is affiliated with the European Society of Clinical Pharmacy (ESCP). ESCP promotes practice and research in Clinical Pharmacy, especially in Europe. The general aim of the society is to advance education, practice and research in Clinical Pharmacy .
Until 2010 the journal was called Pharmacy World & Science.