UMR CNRS 5558, Laboratoire de Biométrie et Biologie Humaine, Équipe Évaluation et Modélisation des Effets Thérapeutiques, rue Guillaume-Paradin, BP8071, 69376 Lyon cedex 08, France; Inserm U1111, National Referral Centre for rare Juvenile Rheumatological and Auto-immune Diseases (RAISE), Department of Paediatric Rheumatology, Lyon University Hospital, University of Lyon, 69677 Bron cedex, France.
UMR CNRS 5558, Laboratoire de Biométrie et Biologie Humaine, Équipe Évaluation et Modélisation des Effets Thérapeutiques, rue Guillaume-Paradin, BP8071, 69376 Lyon cedex 08, France; National Referral Centre for rare Juvenile Rheumatological and Auto-immune Diseases (RAISE), Department of Internal and Vascular Medicine, Hôpital Lyon Sud, Lyon University Hospital, University of Lyon, 69495 Pierre-Bénite, France.
Joint Bone Spine. 2019 May;86(3):343-350. doi: 10.1016/j.jbspin.2018.08.003. Epub 2018 Sep 7.
To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort.
In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan-Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events.
Overall 813 patients totalling 3439 patients-year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events.
This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.
通过真实世界的随访队列，分析并报告炎症性疾病儿科患者使用生物制剂的不良反应发生率。
在这项针对儿童使用生物制剂治疗并在青少年炎症性风湿病（JIR）队列（JIRcohorte）网络中进行随访的国际、观察性、回顾性、多中心研究中，采用 Kaplan-Meier 方法估计不良事件的发生。构建 Cox 模型以确定不良事件的独立预测因素。
共纳入 813 例患者，总计 3439 例患者-年（PY）的生物制剂治疗。主要诊断为幼年特发性关节炎（84%）。共有 222 例（27.3%）患者发生 419 次不良事件，发病率为每 100 PY 12.2（95%CI [11.0; 13.4]）。严重不良事件的总发生率为每 100 PY 3.9（95%CI [3.2; 4.6]）。托珠单抗和英夫利昔单抗与不良事件显著相关，而卡那单抗与严重不良事件相关。不良事件和严重不良事件的单因素和多因素分析表明，同时使用免疫抑制剂（不包括甲氨蝶呤）的生物制剂治疗患者发生这些事件的风险更高。
本研究表明，在接受生物制剂治疗的炎症性风湿病儿童中，生物制剂总体上具有可接受的安全性。然而，生物制剂与免疫抑制剂同时处方代表了发生不良事件的实质性风险。
