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Rheumatoid arthritis
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
  1. Jinjing Liu1,
  2. Ying Jiang1,
  3. Shangzhu Zhang1,
  4. Shengyun Liu2,
  5. Jingbo Su2,
  6. Changsong Lin3,
  7. Xiaohong He4,
  8. Rui Wu5,
  9. Lei Yang6,
  10. Huaxiang Liu7,
  11. Xinwang Duan8,
  12. Shengqian Xu9,
  13. Hui Luo10,
  14. Jing Liu11,
  15. Qibing Xie12,
  16. Cundong Mi13,
  17. Lin Chen14,
  18. Ning Zhang15,
  19. Huiping Gong16,
  20. Jing Zhu17,
  21. Yasong Li18,
  22. Hua Wei19,
  23. Long Qian20,
  24. Jian Wang21,
  25. Xiaofei Shi22,
  26. Hongtao Jin23,
  27. Zhenyu Jiang24,
  28. Xi Xie25,
  29. Feng Zhan26,
  30. Xiuqin Geng27,
  31. Zhaohui Zheng28,
  32. Zhengfu Du29,
  33. Guangchao Dong30,
  34. Yuqi Sun31,
  35. Xiaofeng Zeng1
  1. 1Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China
  2. 2Department of Rheumatology & Immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
  3. 3Department of Rheumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
  4. 4Department of Rheumatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
  5. 5Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
  6. 6Department of Rheumatology and Immunology, Zhengzhou Central Hospital, Zhengzhou, China
  7. 7Rheumatology Department, Qilu Hospital of Shandong University, Jinan, China
  8. 8Rheumatology and Immunology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
  9. 9Rheumatology and Immunology Department, The First Affiliated Hospital of Anhui Medical University, Hefei, China
  10. 10Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, China
  11. 11Department of Rheumatology and Immunology Research Institute, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
  12. 12Department of Rheumatology and Immunology, West China Hospital of Sichuan University, Chengdu, China
  13. 13Department of Rheumatology and Clinical Immunology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, China
  14. 14Department of Rheumatic Immunity, Jilin Province People's Hospital, Changchun, China
  15. 15Rheumatology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China
  16. 16Department of Rheumatology and Clinical Immunology, Peace Hospital Affiliated to Changzhi Medical College, Changzhi, China
  17. 17Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital, Chengdu, China
  18. 18Department of Rheumatology and Clinical Immunology, Zhejiang Provincial People's Hospital, Hangzhou, China
  19. 19Rheumatology and Immunology Department, Northern Jiangsu People's Hospital, Yangzhou, China
  20. 20Department of Rheumatology and Clinical Immunology, The Second Hospital of Anhui Medical University, Anhui, China
  21. 21Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Bengbu Medical College, Anhui, China
  22. 22Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Henan University of Science & Technology, Luoyang, China
  23. 23Department of Rheumatology and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
  24. 24Department of Rheumatic Immunity, The First Hospital of Jilin University, Changchun, China
  25. 25Department of Clinical Immunology, The Second Xiangya Hospital of Central South University, Changsha, China
  26. 26Department of Rheumatology and Immunology, Hainan General Hospital, Haikou, China
  27. 27Department of Rheumatology and Immunology, Xinxiang Central Hospital, Xinxiang, China
  28. 28Department of Clinical Immunology, Xijing Hospital, the Fourth Military Medical University, Xi'an, China
  29. 29Department of Rheumatology and Immunology, Yuncheng Central Hospital, Yuncheng, China
  30. 30Clinical Research & Development, Jiangsu Hengrui Pharmaceuticals, Shanghai, China
  31. 31Biometric Department, Jiangsu Hengrui Pharmaceuticals, Shanghai, China
  1. Correspondence to Dr Xiaofeng Zeng; zengxfpumc@163.com; xiaofeng.zeng@cstar.org.cn

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.

  • Arthritis, Rheumatoid
  • Antirheumatic Agents
  • Health-Related Quality Of Life
  • Autoimmune Diseases

Data availability statement

Data are available upon reasonable request. Data are available upon reasonable request. The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request after the product and indication has been approved by major health authorities. Data may be requested 24 months after study completion. Qualified researchers should submit a proposal to the corresponding author outlining the reasons for requiring the data. The leading clinical site and sponsor will check whether the request is subject to any intellectual property restriction. Use of data must also comply with the requirements of Human Genetics Resources Administration of China and other country or region-specific regulations. A signed data access agreement with the sponsor is required before accessing shared data.

https://doi.org/10.1136/ard-2024-226385

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    Data availability statement

    Data are available upon reasonable request. Data are available upon reasonable request. The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request after the product and indication has been approved by major health authorities. Data may be requested 24 months after study completion. Qualified researchers should submit a proposal to the corresponding author outlining the reasons for requiring the data. The leading clinical site and sponsor will check whether the request is subject to any intellectual property restriction. Use of data must also comply with the requirements of Human Genetics Resources Administration of China and other country or region-specific regulations. A signed data access agreement with the sponsor is required before accessing shared data.

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    Footnotes

    • Handling editor Josef S Smolen

    • Contributors XZ is the guarantor, responsible for the overall content and accepts full responsibility for the work and/or conduct of the study, with access to the data and control over the decision to publish. XZ and GD contributed to design. JinjL (Peking Union Medical College Hospital), YJ, SZ, SL, JS, CL, XH, RW, LY, HLi, XD, SX, HLu, JingL, QX, CM, LC, NZ, HG, JZ, YL, HW, LQ, JW, XS, HJ, ZJ, XX, FZ, XG, ZZ, ZD and XZ contributed to conduct/data collection. YS contributed to statistical analysis. All authors

      contributed to interpretation of data. JinjL and XZ contributed to drafting of the manuscript. All authors were responsible for all content and editorial decisions. Medical writing assistance, under the direction of the authors, and editorial support was provided by Lin Dong, PhD (Jiangsu Hengrui Pharmaceuticals Co, Ltd) according to CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials (https://www.bmj.com/content/340/bmj.c332) and Good Publication Practice guidelines (http://annals.org/aim/article/2424869).

    • Funding NCT04333771 RCT was funded by Jiangsu Hengrui Pharmaceuticals Co, Ltd.

    • Competing interests YS and GD are employees of Jiangsu Hengrui Pharmaceuticals Co, Ltd. All other co-authors declare no competing interest.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.