Matsumura Yumi
Department of Patient Safety, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.
Drug Healthc Patient Saf. 2020 Nov 10;12:207-215. doi: 10.2147/DHPS.S257009. eCollection 2020.
Eculizumab, a drug that blocks activation of the terminal complement pathway, is useful in the treatment of several rare diseases. However, eculizumab-related meningococcal disease is a serious problem. Because of the difficulty diagnosing meningococcal disease, deaths from meningococcal disease may have been overlooked. The purpose of this study was to clarify the trend of meningococcal infection in patients on eculizumab and to evaluate the effectiveness of risk communication.
Pharmacovigilance analysis was conducted using the Japanese Adverse Drug Event Report database between the first quarter of 2010 and the second quarter of 2019. Of the reports of deaths, those with adverse event terms of fever, shock, altered state of consciousness, loss of consciousness, sepsis, organ failure, and disseminated intravascular coagulation were analyzed as deaths with suspected meningococcal infection.
Of the 3559.2 person-years of eculizumab-exposed patients, 17 patients died with symptoms of meningococcal disease (including two confirmed cases). The mortality rate of meningococcal disease in patients exposed to eculizumab in Japan was estimated to be 0.56 (confirmed cases) to 4.8 (suspected cases) per 1000 person-years. Based on data from the National Epidemiological Surveillance of Infectious Disease, the mortality rate of meningococcal disease in the general population in Japan is 0.0042 per 100,000 person-years. Thus, the mortality rate from meningococcal disease in eculizumab-exposed patients is estimated to be 13,000 to 114,000 times the mortality rate from meningococcal disease in the general population of Japan. Academic societies warned of deaths from meningococcal disease in the first quarter of 2018, calling for appropriate action. Thereafter, only one death with symptoms of meningococcal disease has been reported.
The analysis of the database showed that death from meningococcal disease in eculizumab-exposed individuals may occur more often than expected. This study also showed that appropriate risk communication reduced the fatality rate of meningococcal disease.
依库珠单抗是一种可阻断末端补体途径激活的药物，对多种罕见病的治疗有效。然而，依库珠单抗相关的脑膜炎球菌病是一个严重问题。由于脑膜炎球菌病诊断困难，可能有因脑膜炎球菌病导致的死亡被漏诊。本研究的目的是阐明接受依库珠单抗治疗患者的脑膜炎球菌感染趋势，并评估风险沟通的有效性。
利用日本药品不良反应报告数据库对2010年第一季度至2019年第二季度的数据进行药物警戒分析。在死亡报告中，将不良事件术语包含发热、休克、意识改变、意识丧失、败血症、器官衰竭和弥散性血管内凝血的报告分析为疑似脑膜炎球菌感染导致的死亡。
在3559.2人年的依库珠单抗暴露患者中，17例患者死于脑膜炎球菌病症状（包括2例确诊病例）。日本接受依库珠单抗治疗患者的脑膜炎球菌病死亡率估计为每1000人年0.56（确诊病例）至4.8（疑似病例）。根据日本全国传染病流行病学监测数据，日本普通人群中脑膜炎球菌病的死亡率为每10万人年0.0042。因此，接受依库珠单抗治疗患者的脑膜炎球菌病死亡率估计是日本普通人群脑膜炎球菌病死亡率的13000至114000倍。学术团体在2018年第一季度就脑膜炎球菌病导致的死亡发出警告，呼吁采取适当行动。此后，仅报告了1例有脑膜炎球菌病症状的死亡病例。
数据库分析表明，接受依库珠单抗治疗的个体因脑膜炎球菌病死亡的情况可能比预期更常见。本研究还表明，适当的风险沟通降低了脑膜炎球菌病的死亡率。
