Division of Pharmacometrics, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Division of Clinical Pharmacology II, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Clin Pharmacol Ther. 2019 Sep;106(3):557-567. doi: 10.1002/cpt.1302. Epub 2019 Jan 28.
Periodic fever syndromes are a group of rare diseases with a highly variable onset, yet limited treatment options are available for children at an early age. Canakinumab has been approved to treat patients with cryopyrin-associated periodic syndrome, a periodic fever syndrome, and systemic juvenile systemic arthritis, with age cutoffs of 4 years and 2 years, respectively. In 2016, the US Food and Drug Administration (FDA) approved canakinumab, without an age restriction, for the treatment of three conditions of periodic fever syndromes, including familial Mediterranean fever, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and tumor necrosis factor receptor-associated periodic syndrome. This review discusses the pharmacokinetic (PK), efficacy, safety, and exposure-response relationship of canakinumab and provides the rationale for dosage recommendation in children younger than 2 years of age with the three conditions of periodic fever syndromes. The approval of canakinumab for these pediatric patients addresses a critical unmet medical need.
周期性发热综合征是一组罕见疾病,其发病具有高度可变性,但针对儿童的早期治疗选择有限。Canakinumab 已被批准用于治疗 cryopyrin 相关周期性综合征、周期性发热综合征和全身幼年特发性关节炎,其年龄限制分别为 4 岁和 2 岁。2016 年,美国食品和药物管理局 (FDA) 批准了 canakinumab,无年龄限制,用于治疗周期性发热综合征的三种疾病,包括家族性地中海热、高免疫球蛋白 D 综合征/甲羟戊酸激酶缺乏症和肿瘤坏死因子受体相关周期性综合征。本文讨论了 canakinumab 的药代动力学(PK)、疗效、安全性和暴露-反应关系,并为三种周期性发热综合征的 2 岁以下儿童提供了剂量建议的依据。Canakinumab 对这些儿科患者的批准满足了一个关键的未满足的医疗需求。