分析已公开的接受 Janus 激酶抑制剂治疗的儿科患者不良事件报告。
Analysis of publicly available adverse events reported for pediatric patients treated with Janus kinase inhibitors.
机构信息
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Saint Louis University and SSM Cardinal Glennon Children's Hospital, St. Louis, Missouri, USA.
出版信息
Pediatr Dermatol. 2024 Nov-Dec;41(6):1040-1046. doi: 10.1111/pde.15721. Epub 2024 Sep 5.
Janus kinase inhibitors (JAKi) are drugs that block tyrosine kinases responsible for transducing cytokine signals. The first JAKi was approved by the US Food and Drug Administration (FDA) in 2011 to treat rheumatoid arthritis in adults. A pediatric indication was not approved until 8 years later, for acute graft-versus-host disease. Since then, topical and oral formulations have gained FDA approval for pediatric patients with dermatologic diseases. While increasing evidence supports the safety of these medications in adults, data are limited in children. We sought to determine whether JAKi adverse events (AEs) as reported in clinical trials and via postapproval pharmacovigilance services are comparable in adult and pediatric patients. Pharmacovigilance data were extracted from the FDA's Adverse Event Reporting System and the Canada Vigilance Adverse Reaction Online Database for baricitinib, upadacitinib, abrocitinib, ruxolitinib, and tofacitinib. The pooled data were analyzed to detect the most common AEs for specific JAKi and for the drug class. We assessed 399,649 AEs from 133,216 adults and 2883 AEs from 955 patients under 18 years old and identified slightly different AE profiles for the two age groups. Both populations had increased risk for infections and gastrointestinal AEs. However, pediatric patients reported a higher proportion of blood and lymphatic disorders, while reports of nervous system and musculoskeletal/connective tissue disorders were more common in adults. The spectrum of AEs extracted from pharmacovigilance reports was similar to clinical trials. The JAKi AE profiles we observed may prove helpful in counseling patients and their parents before starting therapy and for monitoring once patients are on therapy.
Janus 激酶抑制剂(JAKi)是一类阻断负责转导细胞因子信号的酪氨酸激酶的药物。首个 JAKi 于 2011 年获得美国食品药品监督管理局(FDA)批准,用于治疗成人类风湿关节炎。8 年后才批准其用于儿科患者,适应证为急性移植物抗宿主病。此后,皮肤科疾病的儿童患者又获得了局部用和口服用 JAKi 制剂的 FDA 批准。虽然越来越多的证据支持这些药物在成人中的安全性,但儿童患者的数据有限。我们旨在确定临床试验和上市后药物警戒服务报告的 JAKi 不良事件(AE)在成年和儿科患者中是否具有可比性。从 FDA 的不良事件报告系统和加拿大警戒不良反应在线数据库中提取了巴瑞替尼、乌帕替尼、阿布昔替尼、鲁索利替尼和托法替布的药物警戒数据。对汇总数据进行分析,以检测特定 JAKi 和药物类别最常见的 AE。我们评估了 133216 名成年患者的 399649 例 AE 和 955 名 18 岁以下患者的 2883 例 AE,发现这两个年龄组的 AE 谱略有不同。两个年龄段的患者均存在感染和胃肠道 AE 风险增加的情况。然而,儿科患者报告了更高比例的血液和淋巴系统疾病,而神经系统和肌肉骨骼/结缔组织疾病的报告在成年患者中更为常见。从药物警戒报告中提取的 AE 谱与临床试验相似。我们观察到的 JAKi AE 谱可能有助于在开始治疗前为患者及其家长提供咨询,并在患者开始治疗后进行监测。