Okusa Shohei, Takizawa Tsubasa, Imai Shungo, Oyama Munenori, Ishizuchi Kei, Nakahara Jin, Hori Satoko, Suzuki Shigeaki
Department of Neurology, Keio University School of Medicine, Japan.
Division of Drug Informatics, Keio University Faculty of Pharmacy, Japan.
Intern Med. 2024 Apr 15;63(8):1061-1066. doi: 10.2169/internalmedicine.1893-23. Epub 2023 Sep 8.
Objective Molecular-targeted agents, including eculizumab and rituximab, are considered treatment options for refractory myasthenia gravis (MG), but bacterial infections can occur as serious adverse events when using these agents. The present study elucidated the relative risks of bacterial infections associated with eculizumab and rituximab using a pharmacovigilance database. Methods We analyzed eculizumab- and rituximab-associated adverse events reported between 2007 and 2021 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) and herein report a refractory MG patient who developed streptococcal toxic shock syndrome during eculizumab treatment. Patients We evaluated a 74-year-old Japanese woman with refractory MG who developed severe bacteremia after receiving eculizumab. Results A total of 44,215 and 108,485 adverse events were reported with eculizumab and rituximab, respectively, from among 13,742,321 individual case safety reports in the FAERS database after data cleaning. We found a strong association between eculizumab and Neisseria infections. In contrast, we found only one case of meningococcal meningitis treated with rituximab. Both eculizumab and rituximab were weakly associated with streptococcal infections. Two cases of streptococcal toxic shock syndrome were associated with rituximab. Conclusion Careful monitoring of serious bacterial infections associated with eculizumab treatment is warranted.
目的 包括依库珠单抗和利妥昔单抗在内的分子靶向药物被认为是难治性重症肌无力（MG）的治疗选择，但使用这些药物时可能会发生细菌感染这一严重不良事件。本研究使用药物警戒数据库阐明了与依库珠单抗和利妥昔单抗相关的细菌感染的相对风险。方法 我们分析了2007年至2021年期间在美国食品药品监督管理局不良事件报告系统（FAERS）中报告的与依库珠单抗和利妥昔单抗相关的不良事件，并在此报告1例在依库珠单抗治疗期间发生链球菌中毒性休克综合征的难治性MG患者。患者 我们评估了1例74岁的日本难治性MG女性患者，其在接受依库珠单抗治疗后发生了严重菌血症。结果 在对FAERS数据库中的13,742,321份个体病例安全报告进行数据清理后，分别报告了44,215例和108,485例与依库珠单抗和利妥昔单抗相关的不良事件。我们发现依库珠单抗与奈瑟菌感染之间存在强关联。相比之下，我们仅发现1例接受利妥昔单抗治疗的脑膜炎球菌性脑膜炎病例。依库珠单抗和利妥昔单抗与链球菌感染均存在弱关联。2例链球菌中毒性休克综合征与利妥昔单抗有关。结论 有必要对与依库珠单抗治疗相关的严重细菌感染进行仔细监测。
