Zhang Weidong, Chen Yunzhou, Yao Zeyu, Ouyang Mengling, Sun Minghui, Zou Shupeng
Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, China.
Pharmaceuticals (Basel). 2025 Jan 16;18(1):114. doi: 10.3390/ph18010114.
Canakinumab, a humanized anti-IL-1β monoclonal antibody, is known for its ability to suppress IL-1β-mediated inflammation. However, continuous monitoring of its safety remains essential. Thus, we comprehensively evaluated the safety signals of canakinumab by data mining from FAERS. We used a disproportionate analysis to quantify canakinumab-related adverse events (AEs) using four algorithms. Clinical prioritization of the detected signals was assessed with a semiquantitative score method. Serious and non-serious outcomes were compared by statistical methods. Additionally, a stratification analysis of serious infections was conducted at the system organ class (SOC) level. A total of 28,496 canakinumab-related AEs were collected, and 71 suspicious signals detected. Among these, 19 preferred terms (PTs) were identified as unexpected signals, including deafness, appendicitis, brain oedema, cushingoid, cellulitis, and papilledema. Of the AEs, 16 were more likely reported as serious outcomes, such as pneumonia, abdominal pain, deafness, and infection. Based on clinical priority score, 44 PTs were classified as weak, 27 as moderate, and none as strong. Furthermore, 30 PTs demonstrated a high level of evidence, primarily derived from FDA prescribing information, randomized controlled trials, and systematic reviews. Stratification analysis of infections and infestations (serious outcomes) revealed a stronger association of severe infections with canakinumab in older or heavier individuals. All positive signals followed an early failure pattern, with the incidence of canakinumab-associated AEs decreasing over time. We found that most of the suspicious signals were associated with infections. More attention should be paid to serious infections, particularly in males, individuals aged ≥60 years, or those weighing >100 kg, who demonstrated the highest risk of serious infections.
卡那单抗是一种人源化抗白细胞介素-1β单克隆抗体，以其抑制白细胞介素-1β介导的炎症的能力而闻名。然而，持续监测其安全性仍然至关重要。因此，我们通过从FDA不良事件报告系统（FAERS）中挖掘数据，全面评估了卡那单抗的安全信号。我们使用不成比例分析，通过四种算法对卡那单抗相关不良事件（AE）进行量化。使用半定量评分方法评估检测到的信号的临床优先级。通过统计方法比较严重和非严重结局。此外，在系统器官分类（SOC）水平上对严重感染进行了分层分析。共收集到28496例卡那单抗相关AE，检测到71个可疑信号。其中，19个首选术语（PT）被确定为意外信号，包括耳聋、阑尾炎、脑水肿、库欣样、蜂窝织炎和视乳头水肿。在这些AE中，16个更有可能被报告为严重结局，如肺炎、腹痛、耳聋和感染。根据临床优先级评分，44个PT被分类为弱，27个为中度，没有一个为强。此外，30个PT显示出高水平的证据，主要来自FDA处方信息、随机对照试验和系统评价。感染和侵染（严重结局）的分层分析显示，在年龄较大或体重较重的个体中，严重感染与卡那单抗的关联更强。所有阳性信号均遵循早期失败模式，卡那单抗相关AE的发生率随时间下降。我们发现大多数可疑信号与感染有关。应更多关注严重感染，特别是男性、≥60岁的个体或体重>100 kg的个体，他们显示出严重感染的最高风险。
