Zhong Jinman, Chen Chang, Xu Yunman, He Yueping, Tan Jiewen, Xiong Dan
Department of Hematology, The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan), Foshan, China.
Front Pharmacol. 2025 Aug 11;16:1639685. doi: 10.3389/fphar.2025.1639685. eCollection 2025.
Complement inhibitors are increasingly utilized across various clinical indications, including the treatment of paroxysmal nocturnal hemoglobinuria (PNH). A thorough understanding of their adverse events (AEs) profiles, particularly regarding infections, is essential to ensure safe and effective treatment strategies.
To characterize the real-world AEs profile of complement inhibitors in PNH, with a focus on viral infections characteristics and distinct fatality risk, of while exploring potential implications for viral prophylaxis and identifying risk factors associated with fatal infection-related adverse events.
Complement inhibitor-associated AE cases reported in FAERS between 2004 and 2024 were included. Pharmacovigilance analyses (including Reporting Odds Ratio [ROR] and multiple other metrics) were employed to detect signals for adverse events, including viral infection. Time-to-onset analysis and logistic regression were used to assess temporal patterns and identify factors associated with viral infections and fatal outcomes.
Among 58,613 AE reports, 11,957 (20.4%) were infection-related, and 8.91% were fatal. Infection-related AEs constituted 11,957 cases, predominantly linked to C5 inhibitors. Pharmacovigilance analysis revealed significant disproportionality signals for viral infections (e.g., influenza, herpes zoster, gastroenteritis viral, viral infection). C5 inhibitors had higher cases numbers, but C3 inhibitors demonstrated a stronger signal intensity (ROR = 3.52, 95%CI: 2.54-4.89). Fatal viral AEs had a median time-to-event of 12 days, while non-fatal viral infections occurred later, with a median time-to-event of 187 days. Older age, higher body weight, and treatment initiation in later quarters were associated with reduced viral infection risk, while female was linked to slightly elevated risk. While viral infections were common concomitant AEs, the fatality rate specifically for viral infections was lower compared to other complement inhibitor-associated AEs. Advanced age (≥75 years), treatment initiation in the third quarter and C5 inhibitor use were identified as significant risk factors for fatal infectious outcomes, whereas female sex and higher body weight appeared protective.
Complement inhibitors, particularly C3 agents, are associated with significant reporting of infectious AEs in FAERS, including specific viral infections like influenza and herpes. Early onset of viral AEs highlights the need for vigilance early in treatment. While advanced age and C5 use heighten mortality risk, the attenuated lethality of viral AEs suggests a distinct pathophysiological interplay warranting mechanistic study. The divergent risk profiles between C3 and C5 inhibitors underscore the need for personalized risk-benefit assessments in complement inhibition strategies.
补体抑制剂在包括阵发性夜间血红蛋白尿（PNH）治疗在内的各种临床适应症中使用越来越广泛。全面了解其不良事件（AE）特征，尤其是关于感染方面的特征，对于确保安全有效的治疗策略至关重要。
描述PNH中补体抑制剂的真实世界AE特征，重点关注病毒感染特征和不同的死亡风险，同时探索对病毒预防的潜在影响，并确定与致命感染相关不良事件相关的风险因素。
纳入2004年至2024年期间在FAERS中报告的补体抑制剂相关AE病例。采用药物警戒分析（包括报告比值比[ROR]和其他多种指标）来检测不良事件信号，包括病毒感染。使用发病时间分析和逻辑回归来评估时间模式，并确定与病毒感染和致命结局相关的因素。
在58,613份AE报告中，11,957例（20.4%）与感染相关，8.91%为致命事件。感染相关AE构成11,957例，主要与C5抑制剂有关。药物警戒分析揭示了病毒感染（如流感、带状疱疹、病毒性肠胃炎、病毒感染）的显著不成比例信号。C5抑制剂的病例数较多，但C3抑制剂显示出更强的信号强度（ROR = 3.52，95%CI：2.54 - 4.89）。致命性病毒AE的中位发病时间为12天，而非致命性病毒感染发生较晚，中位发病时间为187天。年龄较大、体重较高以及在后期季度开始治疗与病毒感染风险降低相关，而女性则与风险略有升高相关。虽然病毒感染是常见的伴随AE，但与其他补体抑制剂相关AE相比，病毒感染的死亡率较低。高龄（≥75岁）、第三季度开始治疗和使用C5抑制剂被确定为致命感染结局的重要风险因素，而女性和较高体重似乎具有保护作用。
补体抑制剂，尤其是C3制剂，在FAERS中与感染性AE的显著报告相关，包括流感和疱疹等特定病毒感染。病毒AE的早期发生凸显了治疗早期保持警惕的必要性。虽然高龄和使用C5会增加死亡风险，但病毒AE的致死率降低表明存在独特的病理生理相互作用，值得进行机制研究。C3和C5抑制剂之间不同的风险特征强调了在补体抑制策略中进行个性化风险效益评估的必要性。
