Carrillo Infante Cynthia, Mujeebuddin Arshad
Global Patient Safety, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, United States of America.
PLoS One. 2025 Sep 12;20(9):e0332073. doi: 10.1371/journal.pone.0332073. eCollection 2025.
Complement component 5 inhibitor therapies (C5ITs) for rare hematological, renal, and neurological diseases are associated with increased meningococcal infection risk. Robust risk mitigation measures include vaccination, drug safety programs, patient safety cards, and antibiotic prophylaxis initiation when starting C5ITs. Here we describe the exposure-adjusted meningococcal infection and mortality rates in eculizumab- or ravulizumab-treated patients based on clinical trial and real-world pharmacovigilance data.
Global clinical trial and real-world safety data regarding eculizumab and ravulizumab use across indications were recorded in the Alexion pharmacovigilance database. Data for eculizumab (March 2007-October 2024) and ravulizumab (December 2018-December 2024) were searched based on the Medical Dictionary for Regulatory Activities (versions 26.1, 27.0, and 27.1) High-Level Term of Neisseria infection. Only cases associated with Neisseria meningitidis were included. Reporting rates were calculated cumulatively per 100 patient-years (PY).
At the time of analysis, cumulative exposure across clinical trial and real-world settings were 2457 and 91,052 PY, respectively, for eculizumab and 3287 and 34,582 PY, respectively, for ravulizumab. The cumulative meningococcal infection rate in clinical trials was 0.28 and 0.18 per 100 PY for eculizumab and ravulizumab, respectively. Real-world cumulative meningococcal infection rates in patients treated with eculizumab have decreased since 2007 (0.25 per 100 PY in 2024). In patients treated with ravulizumab, the real-world cumulative rate of meningococcal infection remains low (0.10 per 100 PY in 2024). The rates of meningococcal-associated mortality were ≤0.03 per 100 PY in both eculizumab- and ravulizumab-treated patients in clinical trials and real-world settings.
Meningococcal infection and mortality reporting rates have remained stable despite increasing cumulative eculizumab and ravulizumab exposure over time across indications, including rare neurological indications. Infection awareness, existing risk mitigation strategies, and availability of vaccines have effectively reduced the risk of meningococcal infections in C5IT-treated patients, underlining the importance of adhering to those measures.
用于治疗罕见血液、肾脏和神经系统疾病的补体成分5抑制剂疗法（C5ITs）会增加脑膜炎球菌感染风险。强有力的风险缓解措施包括接种疫苗、药物安全计划、患者安全卡以及在开始使用C5ITs时启动抗生素预防。在此，我们根据临床试验和真实世界药物警戒数据，描述接受依库珠单抗或ravulizumab治疗患者的暴露调整后脑膜炎球菌感染率和死亡率。
关于依库珠单抗和ravulizumab在各适应症中的使用情况的全球临床试验和真实世界安全数据记录在Alexion药物警戒数据库中。根据《监管活动医学词典》（第26.1版、第27.0版和第27.1版）中奈瑟菌感染的高级术语，搜索依库珠单抗（2007年3月至2024年10月）和ravulizumab（2018年12月至2024年12月）的数据。仅纳入与脑膜炎奈瑟菌相关的病例。报告率按每100患者年（PY）累计计算。
在分析时，依库珠单抗在临床试验和真实世界环境中的累计暴露量分别为2457 PY和91,052 PY，ravulizumab分别为3287 PY和34,582 PY。依库珠单抗和ravulizumab在临床试验中的累计脑膜炎球菌感染率分别为每100 PY 0.28例和0.18例。自2007年以来，接受依库珠单抗治疗患者的真实世界累计脑膜炎球菌感染率有所下降（2024年为每100 PY 0.25例）。在接受ravulizumab治疗的患者中，真实世界的脑膜炎球菌感染累计率仍然较低（2024年为每100 PY 0.10例）。在临床试验和真实世界环境中，接受依库珠单抗和ravulizumab治疗的患者中，脑膜炎球菌相关死亡率均≤每100 PY 0.03例。
尽管随着时间推移，依库珠单抗和ravulizumab在各适应症（包括罕见神经系统适应症）中的累计暴露量不断增加，但脑膜炎球菌感染和死亡率报告率保持稳定。感染意识、现有的风险缓解策略以及疫苗的可及性有效降低了接受C5ITs治疗患者的脑膜炎球菌感染风险，凸显了坚持这些措施的重要性。
