1 Binghamton University School of Pharmacy and Pharmaceutical Sciences, Binghamton, NY, USA.
2 Rhode Island Hospital, Providence, RI, USA.
Ann Pharmacother. 2019 Sep;53(9):947-953. doi: 10.1177/1060028019839650. Epub 2019 Mar 24.
To review the pharmacology, pharmacokinetics, safety, and efficacy of baricitinib, a recently approved selective Janus Kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA), and explore its potential role in therapy. Articles were identified using a PubMed search from inception through January 2019 using the terms , and , its molecular name. Articles relating to randomized clinical trials, pharmacology, pharmacokinetics, efficacy, and safety of baricitinib were evaluated. Baricitinib exerts its effects by inhibiting JAK1 and JAK2 enzymes, targeting cytokine and growth factor receptor stimulation, thus reducing downstream immune cell function. Four trials have demonstrated the efficacy of baricitinib with or without methotrexate in patients naïve to disease-modifying antirheumatic drugs (DMARDs) and those who had an inadequate response to or intolerance to both conventional and biological DMARDs. Furthermore, baricitinib was associated with delayed radiographic progression. Despite baricitinib 4 mg often demonstrating greater efficacy compared with the 2 mg dose, only the 2 mg dose is Food and Drug Administration approved because of safety concerns with the 4 mg dose, primarily thromboembolism. Baricitinib provides an oral treatment option for patients failing tumor necrosis factor inhibitors (TNFis). Safety, cost, and comparative effectiveness to tofacitinib should be considered prior to prescribing baricitinib. Baricitinib is the second medication in its class and has been proven efficacious for the treatment of RA. Given concerns for adverse effects associated with baricitinib, it should be reserved for patients who have failed one or more TNFis.
回顾巴瑞替尼的药理学、药代动力学、安全性和疗效,巴瑞替尼是一种最近批准的选择性 Janus 激酶(JAK)抑制剂,用于治疗类风湿关节炎(RA),并探讨其在治疗中的潜在作用。使用 PubMed 从开始到 2019 年 1 月的术语和其分子名称进行了文献检索。评估了与随机临床试验、药理学、药代动力学、疗效和巴瑞替尼安全性相关的文章。巴瑞替尼通过抑制 JAK1 和 JAK2 酶发挥作用,靶向细胞因子和生长因子受体刺激,从而降低下游免疫细胞功能。四项试验表明,巴瑞替尼联合或不联合甲氨蝶呤在初治疾病修饰抗风湿药物(DMARDs)和对常规和生物 DMARDs 反应不足或不耐受的患者中有效。此外,巴瑞替尼与放射学进展延迟有关。尽管巴瑞替尼 4mg 与 2mg 剂量相比通常具有更大的疗效,但仅批准 2mg 剂量,因为 4mg 剂量存在安全问题,主要是血栓栓塞。巴瑞替尼为肿瘤坏死因子抑制剂(TNFis)治疗失败的患者提供了一种口服治疗选择。在开处方巴瑞替尼之前,应考虑安全性、成本和与托法替尼的比较效果。巴瑞替尼是其同类药物中的第二种药物,已被证明对治疗 RA 有效。鉴于与巴瑞替尼相关的不良反应的担忧,它应保留给已使用一种或多种 TNFis 治疗失败的患者。