Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial.
Jinjing Liu, Ying Jiang, Shangzhu Zhang, Shengyun Liu, Jingbo Su, Changsong Lin, Xiaohong He, Rui Wu, Lei Yang, Huaxiang Liu, Xinwang Duan, Shengqian Xu, Hui Luo, Jing Liu, Qibing Xie, Cundong Mi, Lin Chen, Ning Zhang, Huiping Gong, Jing Zhu, Yasong Li, Hua Wei, Long Qian, Jian Wang, Xiaofei Shi, Hongtao Jin, Zhenyu Jiang, Xi Xie, Feng Zhan, Xiuqin Geng, Zhaohui Zheng, Zhengfu Du, Guangchao Dong, Yuqi Sun, Xiaofeng Zeng
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引用次数: 0
Abstract
Objective: To assess the efficacy/safety of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).
Methods: Patients were randomised (1:1:1) to receive either placebo (n=188), ivarmacitinib 4 mg (n=189) or ivarmacitinib 8 mg (n=189) once daily, with background csDMARDs allowed. After 24 weeks, patients on placebo switched to ivarmacitinib 4 mg for an additional 28 weeks, while those on ivarmacitinib continued their initial dosage. The primary endpoint was the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24.
Results: At week 24, ACR20 response rates were significantly higher in the ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) groups compared with the placebo group (40.4%; both p<0.0001). Both ivarmacitinib doses achieved numerically higher Disease Activity Score 28-joint count C reactive protein of <2.6/≤3.2 response rates compared with placebo. Improvements in efficacy and patient-reported outcomes were sustained through 52 weeks and were noted in patients who switched from placebo after week 24. During the placebo-controlled period, treatment-emergent adverse events (TEAEs) occurred in 81.5% and 90.5% of patients in the ivarmacitinib 4 mg and 8 mg groups, versus 79.3% in the placebo group. Infection-related TEAEs were slightly higher in the ivarmacitinib groups.
Conclusions: Ivarmacitinib may offer a potential therapeutic option for patients with RA who have an inadequate response to csDMARDs, with a safety profile that was generally manageable over 1 year of treatment and similar to other JAK inhibitors.
期刊介绍：
Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.
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