Liu Qian, Wang Yang, Hu Panwei, He Peizhi
Department of Obstetrics and Gynecology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Reproductive Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Drug Discov Ther. 2025 Jul 4;19(3):160-173. doi: 10.5582/ddt.2025.01043. Epub 2025 Jun 29.
Biologics are essential for managing immune-related inflammatory diseases during pregnancy to prevent disease progression and adverse pregnancy outcomes. However, data on the safety of biologics in a broader population are limited. This study aims to evaluate abortion-related adverse events (AEs) associated with adalimumab, etanercept, ustekinumab, and dupilumab, using data from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed using the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) to identify signals of abortion-related AEs. The time-to-onset profiles were assessed by analyzing the description and Weibull shape parameters (WSPs) for these events. Sensitivity analyses were also conducted, including drug-drug interaction studies, logistic regression, and a similar retrospective analysis using data from the Japanese Adverse Drug Event Report (JADER) database. Disproportionality analysis revealed specific signals for abortion-related AEs associated with adalimumab, etanercept, and ustekinumab. The drug-drug interaction analysis indicated that these biologics, particularly without methotrexate or prednisolone, increase the risk of abortion-related AEs. Logistic regression identified several factors influencing outcomes. The time-to-onset analysis revealed that dupilumab had an earlier onset of 62.5 days, while etanercept had a later onset at 184 days. WSPs analysis revealed that signals for adalimumab, ustekinumab, and dupilumab exhibited early failure-type features, indicating a decreasing risk of abortion-related AEs over time. In conclusion, adalimumab, etanercept, and ustekinumab are associated with an increased risk of abortion-related adverse pregnancy outcomes, though the signals remain relatively weak. Further large-scale studies are needed to provide more definitive evidence.
生物制剂对于孕期管理免疫相关炎症性疾病以预防疾病进展和不良妊娠结局至关重要。然而，关于生物制剂在更广泛人群中的安全性数据有限。本研究旨在使用美国食品药品监督管理局不良事件报告系统（FAERS）数据库中的数据，评估与阿达木单抗、依那西普、乌司奴单抗和度普利尤单抗相关的流产相关不良事件（AE）。使用报告比值比（ROR）和贝叶斯置信传播神经网络（BCPNN）进行不成比例分析，以识别流产相关AE的信号。通过分析这些事件的描述和威布尔形状参数（WSP）来评估发病时间概况。还进行了敏感性分析，包括药物相互作用研究、逻辑回归以及使用日本药品不良事件报告（JADER）数据库数据进行的类似回顾性分析。不成比例分析揭示了与阿达木单抗、依那西普和乌司奴单抗相关的流产相关AE的特定信号。药物相互作用分析表明，这些生物制剂，尤其是在没有甲氨蝶呤或泼尼松龙的情况下，会增加流产相关AE的风险。逻辑回归确定了几个影响结局的因素。发病时间分析显示，度普利尤单抗的发病时间较早，为62.5天，而依那西普的发病时间较晚，为184天。WSPs分析显示，阿达木单抗、乌司奴单抗和度普利尤单抗的信号呈现早期失效型特征，表明随着时间推移，流产相关AE的风险降低。总之，阿达木单抗、依那西普和乌司奴单抗与流产相关不良妊娠结局的风险增加有关，尽管这些信号仍然相对较弱。需要进一步的大规模研究来提供更确凿的证据。
