Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden.
Drugs Today (Barc). 2020 Nov;56(11):723-732. doi: 10.1358/dot.2020.56.11.3191007.
In rheumatoid arthritis (RA) there is an unmet therapeutic need, as a substantial proportion of patients does not achieve low disease activity or remission despite the use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or biological DMARDs (bDMARDs). The Janus kinase (JAK) inhibitors are the most recently added drug category in the therapeutic armamentarium in RA. Upadacitinib tartrate (Rinvoq), a selective and reversible JAK1 inhibitor, inhibited interleukin (IL)-6 and IL-7 and ameliorated adjuvant-induced arthritis in preclinical studies. In phase III randomized controlled trials (RCTs), upadacitinib, as monotherapy or in combination with csDMARDs, showed efficacy in RA patients with inadequate response to csDMARDs or bDMARDs. In a head-to-head RCT, upadacitinib 15 mg once daily was superior to adalimumab in achieving remission and in patient-reported outcomes. Upadacitinib has a good safety profile but it may increase the risk for herpes zoster, and as a substrate of cytochrome P450 (CYP) enzyme CYP3A4 it should not be coadministered with strong CYP3A4 inducers. Upadacitinib is contraindicated in patients with active tuberculosis, serious infections, active malignancy and in patients with severe liver impairment. Upadacitinib has been approved for the treatment of moderate to severe RA.
在类风湿关节炎（RA）中，存在着未满足的治疗需求，因为尽管使用了传统的合成疾病修饰抗风湿药物（csDMARDs）和/或生物 DMARDs（bDMARDs），仍有相当一部分患者无法达到低疾病活动度或缓解。Janus 激酶（JAK）抑制剂是 RA 治疗武器库中最近添加的药物类别。盐形式的托法替布（Rinvoq），一种选择性和可逆的 JAK1 抑制剂，在临床前研究中抑制白细胞介素（IL）-6 和 IL-7，并改善佐剂诱导的关节炎。在 III 期随机对照试验（RCT）中，托法替布单药或与 csDMARDs 联合治疗，在 csDMARDs 或 bDMARDs 应答不足的 RA 患者中显示出疗效。在一项头对头 RCT 中，每日一次 15mg 托法替布在达到缓解和患者报告的结局方面优于阿达木单抗。托法替布具有良好的安全性，但它可能会增加带状疱疹的风险，并且作为细胞色素 P450（CYP）酶 CYP3A4 的底物，不应与强 CYP3A4 诱导剂同时使用。托法替布禁用于活动性结核病、严重感染、活动性恶性肿瘤和严重肝损伤患者。托法替布已被批准用于治疗中度至重度 RA。
