主要用于过敏性鼻炎和哮喘的白三烯受体拮抗剂药品不良反应报告的比较分析：一项WHO VigiAccess研究

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中文摘要

背景： 白三烯受体拮抗剂（LTRAs），包括孟鲁司特、普仑司特和扎鲁司特，通常耐受性良好，广泛用于哮喘和过敏性鼻炎，但可能引起药品不良反应（ADRs）。我们比较了它们的真实世界报告特征，以识别潜在的药物特异性安全性差异。
方法： 我们对2025年8月1日检索的世界卫生组织（WHO）VigiAccess数据进行了描述性和不成比例分析。纳入报告的时间范围为每种药物在VigiAccess中可获取的首年（扎鲁司特，1997年；孟鲁司特，1998年；普仑司特，2002年）至2025年8月1日。报告层面的 demographics 使用个例安全性报告（ICSRs）数量进行总结，而系统器官分类（SOC）和首选术语（PT）层面的百分比则以相应药物的ADR条目总数为分母。报告比值比（RORs）、比例报告比（PRRs）和95%置信区间（CIs）将每种目标LTRA与另外两种LTRA合并进行比较。
结果： 我们识别出37,621份ICSRs：孟鲁司特33,615份（89.4%）；普仑司特2,109份（5.6%）；扎鲁司特1,897份（5.0%）。在96,624条孟鲁司特ADR条目中，SOC精神疾病类占n = 29,498（30.5%）。PT层面的阳性信号包括噩梦（n = 1,688，1.75%；ROR = 45.89，95% CI：14.78-142.45；PRR = 45.10，95% CI：14.53-139.95）、攻击性（n = 1,758，1.82%；ROR = 28.69，95% CI：11.92-69.03；PRR = 28.18，95% CI：11.72-67.78）和自杀意念（n = 1,901，1.97%；ROR = 19.41，95% CI：9.69-38.88；PRR = 19.05，95% CI：9.52-38.13）。在2,724条普仑司特ADR条目中，胃肠道疾病类占n = 809（29.7%）。扎鲁司特显示出不成比例的肝胆系统报告（ROR = 5.87，95% CI：4.88-7.06；PRR = 5.72，95% CI：4.78-6.85）。七种神经精神类PT在三种药物中均有报告；其计数、ADR条目比例和ROR范围分别为：孟鲁司特569至2,313、0.59%-2.39%、1.22-19.41；普仑司特2-99、0.07%-3.63%、0.03-1.82；扎鲁司特4-35、0.08%-0.70%、0.06-0.32。
结论： 来自自发报告数据库的真实世界证据提示孟鲁司特、普仑司特和扎鲁司特的安全性报告特征存在差异。然而，低报告率和临床信息不完整妨碍了发生率估计或因果推断；这些发现应被解释为安全性信号。

英文摘要

BACKGROUND: Leukotriene receptor antagonists (LTRAs), including montelukast, pranlukast, and zafirlukast, are generally well tolerated and widely used for asthma and allergic rhinitis, but they may cause adverse drug reactions (ADRs). We compared their real-world reporting profiles to identify potential agent-specific safety differences.
METHODS: We conducted a descriptive and disproportionality analysis of World Health Organization (WHO) VigiAccess data retrieved on August 1, 2025. Reports were included from each drug's first year available in VigiAccess (zafirlukast, 1997; montelukast, 1998; pranlukast, 2002) through August 1, 2025. Report-level demographics were summarized using the number of individual case safety reports (ICSRs), whereas System Organ Class (SOC)- and Preferred Term (PT)-level percentages used the total number of ADR entries for the corresponding drug as the denominator. Reporting odds ratios (RORs), proportional reporting ratios (PRRs), and 95% confidence intervals (CIs) compared each target LTRA with the other two LTRAs combined.
RESULTS: We identified 37,621 ICSRs: montelukast, 33,615 (89.4%); pranlukast, 2,109 (5.6%); and zafirlukast, 1,897 (5.0%). Among 96,624 montelukast ADR entries, the SOC Psychiatric disorders accounted for n = 29,498 (30.5%). Positive PT-level signals included nightmares (n = 1,688, 1.75%; ROR = 45.89, 95% CI: 14.78-142.45; PRR = 45.10, 95% CI: 14.53-139.95), aggression (n = 1,758, 1.82%; ROR = 28.69, 95% CI: 11.92-69.03; PRR = 28.18, 95% CI: 11.72-67.78), and suicidal ideation (n = 1,901, 1.97%; ROR = 19.41, 95% CI: 9.69-38.88; PRR = 19.05, 95% CI: 9.52-38.13). Among 2,724 pranlukast ADR entries, Gastrointestinal disorders accounted for n = 809 (29.7%). Zafirlukast showed disproportionate hepatobiliary reporting (ROR = 5.87, 95% CI: 4.88-7.06; PRR = 5.72, 95% CI: 4.78-6.85). Seven neuropsychiatric PTs were shared across all three agents; their counts, ADR-entry proportions, and RORs ranged from 569 to 2,313, 0.59%-2.39%, and 1.22-19.41 for montelukast; 2-99, 0.07%-3.63%, and 0.03-1.82 for pranlukast; and 4-35, 0.08%-0.70%, and 0.06-0.32 for zafirlukast.
CONCLUSIONS: Real-world evidence from spontaneous-report databases suggests differences in the safety-reporting profiles of montelukast, pranlukast, and zafirlukast. However, under-reporting and incomplete clinical information preclude estimation of incidence or causal inference; these findings should be interpreted as safety signals.