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

doi:10.1136/ard-2024-226385

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

Ann Rheum Dis. 2024 Nov 27:ard-2024-226385. doi: 10.1136/ard-2024-226385. Online ahead of print.

Authors

Jinjing Liu¹, Ying Jiang¹, Shangzhu Zhang¹, Shengyun Liu², Jingbo Su², Changsong Lin³, Xiaohong He⁴, Rui Wu⁵, Lei Yang⁶, Huaxiang Liu⁷, Xinwang Duan⁸, Shengqian Xu⁹, Hui Luo¹⁰, Jing Liu¹¹, Qibing Xie¹², Cundong Mi¹³, Lin Chen¹⁴, Ning Zhang¹⁵, Huiping Gong¹⁶, Jing Zhu¹⁷, Yasong Li¹⁸, Hua Wei¹⁹, Long Qian²⁰, Jian Wang²¹, Xiaofei Shi²², Hongtao Jin²³, Zhenyu Jiang²⁴, Xi Xie²⁵, Feng Zhan²⁶, Xiuqin Geng²⁷, Zhaohui Zheng²⁸, Zhengfu Du²⁹, Guangchao Dong³⁰, Yuqi Sun³¹, Xiaofeng Zeng³²

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China.
² Department of Rheumatology & Immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁴ Department of Rheumatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
⁵ Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
⁶ Department of Rheumatology and Immunology, Zhengzhou Central Hospital, Zhengzhou, China.
⁷ Rheumatology Department, Qilu Hospital of Shandong University, Jinan, China.
⁸ Rheumatology and Immunology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
⁹ Rheumatology and Immunology Department, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
¹⁰ Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China.
¹¹ Department of Rheumatology and Immunology Research Institute, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
¹² Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu, China.
¹³ Department of Rheumatology and Clinical Immunology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China.
¹⁴ Department of Rheumatic Immunity, Jilin Province People's Hospital, Changchun, China.
¹⁵ Rheumatology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.
¹⁶ Department of Rheumatology and Clinical Immunology, Peace Hospital Affiliated to Changzhi Medical College, Changzhi, China.
¹⁷ Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, Chengdu, China.
¹⁸ Department of Rheumatology and Clinical Immunology, Zhejiang Provincial People's Hospital, Hangzhou, China.
¹⁹ Rheumatology and Immunology Department, Northern Jiangsu People's Hospital, Yangzhou, China.
²⁰ Department of Rheumatology and Clinical Immunology, The Second Hospital of Anhui Medical University, Anhui, China.
²¹ Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Bengbu Medical College, Anhui, China.
²² Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Henan University of Science & Technology, Luoyang, China.
²³ Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
²⁴ Department of Rheumatic Immunity, The First Hospital of Jilin University, Changchun, China.
²⁵ Department of Clinical Immunology, The Second Xiangya Hospital of Central South University, Changsha, China.
²⁶ Department of Rheumatology and Immunology, Hainan General Hospital, Haikou, China.
²⁷ Department of Rheumatology and Immunology, Xinxiang Central Hospital, Xinxiang, China.
²⁸ Department of Clinical Immunology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.
²⁹ Department of Rheumatology and Immunology, Yuncheng Central Hospital, Yuncheng, China.
³⁰ Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals, Shanghai, China.
³¹ Biometric Department, Jiangsu Hengrui Pharmaceuticals, Shanghai, China.
³² Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China [email protected] [email protected].

PMID: 39603709
DOI: 10.1136/ard-2024-226385

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.

Trial registration number: NCT04333771.

Keywords: Antirheumatic Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Health-Related Quality Of Life.

Associated data

ClinicalTrials.gov/NCT04333771