Abstract：
BACKGROUND: The incidence of clozapine-associated myocarditis varies by country. These variations were explored in VigiBase, the World Health Organization\'s global database which has >25 million spontaneously reported adverse drug reaction (ADR) reports from 145 national drug agencies.
METHODS: On January 15, 2021, a search of VigiBase since inception focused on myocarditis in clozapine patients. The 3572 individual reports were studied using the standard VigiBase logarithmic measure of disproportionality called information component (IC). The IC measures the disproportionality between the expected and the reported rates. After duplicates were eliminated there were 3274 different patients with myocarditis studied in logistic regression models.
RESULTS: The first case was published in 1980 but since 1993 the VigiBase clozapine-myocarditis IC has been significant; moreover, currently it is very strong (IC=6.0, IC005-IC995=5.9-6.1) and statistically significantly different from other antipsychotics. Of the 3274 different patients with myocarditis, 43.4% were non-serious cases, 51.8% were serious but non-fatal, and 4.8% were fatal. More than half (1621/3274) of the reports came from Australia, of which 69.2% were non-serious, 27.7% serious but non-fatal, and 3.1% fatal. Asian countries contributed only 41 cases.
CONCLUSIONS: In pharmacovigilance studies, confounding factors may explain statistical associations, but the strength and robustness of these results are compatible with the hypothesis that myocarditis is definitively associated with early clozapine treatment (84% [1309/1560] and 5% [82/1560] in the first and second months). Myocarditis reports from Australia are over-represented to a major degree. Asian countries may be underreporting myocarditis to their drug agencies.
METHODS: On January 15, 2021, a search of VigiBase since inception focused on myocarditis in clozapine patients. The 3572 individual reports were studied using the standard VigiBase logarithmic measure of disproportionality called information component (IC). The IC measures the disproportionality between the expected and the reported rates. After duplicates were eliminated there were 3274 different patients with myocarditis studied in logistic regression models.
RESULTS: The first case was published in 1980 but since 1993 the VigiBase clozapine-myocarditis IC has been significant; moreover, currently it is very strong (IC=6.0, IC005-IC995=5.9-6.1) and statistically significantly different from other antipsychotics. Of the 3274 different patients with myocarditis, 43.4% were non-serious cases, 51.8% were serious but non-fatal, and 4.8% were fatal. More than half (1621/3274) of the reports came from Australia, of which 69.2% were non-serious, 27.7% serious but non-fatal, and 3.1% fatal. Asian countries contributed only 41 cases.
CONCLUSIONS: In pharmacovigilance studies, confounding factors may explain statistical associations, but the strength and robustness of these results are compatible with the hypothesis that myocarditis is definitively associated with early clozapine treatment (84% [1309/1560] and 5% [82/1560] in the first and second months). Myocarditis reports from Australia are over-represented to a major degree. Asian countries may be underreporting myocarditis to their drug agencies.
摘要：
背景：氯氮平相关性心肌炎的发病率因国家而异。这些变化在VigiBase中进行了探索，世界卫生组织的全球数据库有超过2500万份自发报告的药物不良反应（ADR）来自145个国家药品机构。
方法：2021年1月15日，自成立以来，对VigiBase的搜索集中在氯氮平患者的心肌炎。使用称为信息分量（IC）的标准VigiBase对数不相称性度量对3572份单独报告进行了研究。IC衡量的是预期利率和报告利率之间的不相称性。消除重复项后，在逻辑回归模型中研究了3274名不同的心肌炎患者。
结果：第一例发表于1980年，但自1993年以来，VigiBase氯氮平-心肌炎IC已成为重要的病例；此外，目前它非常强(IC=6.0,IC005-IC995=5.9-6.1),与其他抗精神病药物有统计学差异.在3274名不同的心肌炎患者中，43.4％为非严重病例，51.8%为严重但非致命性,4.8%是致命的。超过一半（1621/3274）的报告来自澳大利亚，其中69.2%为非严重，27.7％严重但非致命，3.1%致命。亚洲国家仅提供了41例病例。
结论：在药物警戒研究中，混杂因素可以解释统计关联，但这些结果的强度和稳健性与心肌炎与早期氯氮平治疗明确相关的假设一致(第1个月和第2个月分别为84%[1309/1560]和5%[82/1560]).来自澳大利亚的心肌炎报告在很大程度上代表过多。亚洲国家可能向其药物机构漏报心肌炎。
方法：2021年1月15日，自成立以来，对VigiBase的搜索集中在氯氮平患者的心肌炎。使用称为信息分量（IC）的标准VigiBase对数不相称性度量对3572份单独报告进行了研究。IC衡量的是预期利率和报告利率之间的不相称性。消除重复项后，在逻辑回归模型中研究了3274名不同的心肌炎患者。
结果：第一例发表于1980年，但自1993年以来，VigiBase氯氮平-心肌炎IC已成为重要的病例；此外，目前它非常强(IC=6.0,IC005-IC995=5.9-6.1),与其他抗精神病药物有统计学差异.在3274名不同的心肌炎患者中，43.4％为非严重病例，51.8%为严重但非致命性,4.8%是致命的。超过一半（1621/3274）的报告来自澳大利亚，其中69.2%为非严重，27.7％严重但非致命，3.1%致命。亚洲国家仅提供了41例病例。
结论：在药物警戒研究中，混杂因素可以解释统计关联，但这些结果的强度和稳健性与心肌炎与早期氯氮平治疗明确相关的假设一致(第1个月和第2个月分别为84%[1309/1560]和5%[82/1560]).来自澳大利亚的心肌炎报告在很大程度上代表过多。亚洲国家可能向其药物机构漏报心肌炎。
