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Comparison of the efficacy and safety of the adalimumab biosimilar TQ-Z2301 and adalimumab for the treatment of Chinese patients with active ankylosing spondylitis: a multi-center, randomized, double-blind, phase III clinical trial

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Abstract

Objective

To assess the clinical equivalence of TQ-Z2301, a biosimilar of adalimumab, to the reference adalimumab in the treatment of Chinese patients with active ankylosing spondylitis.

Methods

This multicenter, randomized, double-blind, positive-controlled phase III clinical trial was conducted in 19 centers across China. Chinese adults with active ankylosing spondylitis despite being treated with non-steroidal anti-inflammatory drugs for ≥ 4 weeks were randomized in a 1:1 ratio to subcutaneously receive 40 mg of TQ-Z2301 or adalimumab every other week for 24 weeks. The primary endpoint was the percentage of patients who achieved at least 20% improvement according to the Assessment of Spondyloarthritis International Society criteria (ASAS20) at week 24. The equivalence was established if the 90% CI for RR of ASAS20 between two groups at week 24 fell within (0.80, 1.25). Secondary endpoints included efficacy measures of disease activity, spinal mobility, physical function and quality of life, immunogenicity, and pharmacokinetic parameters. Safety analysis was done for all patients who received at least one study drug.

Results

A total of 380 patients were enrolled in the study between September 2018 and October 2019, including 188 in the TQ-Z2301 group and 192 in the adalimumab group. In the full analysis population, the ASAS20 response rate at week 24 was 86.70% in the TQ-Z2301 group, and 80.73% in the adalimumab group, the RR of ASAS20 for TQ-Z2301 versus adalimumab was 1.074, 90% CI (0.997, 1.157), fell within the predefined equivalence boundary (0.80, 1.25). Except for the SF-36 at week 12, there was no statistical difference between the two groups for all the secondary endpoints (P>0.05). The incidence of adverse events group was 82.45% in the TQ-Z2301, and 83.85% in the adalimumab group, the safety profile of the two groups was similar. The profiles of immunogenicity and pharmacokinetics were also similar between the two groups.

Conclusion

TQ-Z2301 is equivalent to adalimumab for the treatment of Chinese patients with active ankylosing spondylitis. The safety, immunogenicity, and pharmacokinetic characteristics of both drugs are similar.

Trial registration

The study (CTR20181863) was registered in the Chinese Clinical Trial Registry on 19 October 2018.

Key Points

• TQ-Z2301 showed the equivalence of efficacy compared with the reference adalimumab for the treatment of Chinese patients with active ankylosing spondylitis.

• The safety, immunogenicity, and pharmacokinetics profiles of TQZ-2301 were similar to those of the reference adalimumab.

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Data Availability

The datasets analyzed for this study regarding the efficacy and safety of treatment are available from Dr. Chunde Bao (baochunde_1678@126.com) upon reasonable request.

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Acknowledgements

This study was supported by Chia Tai Tianqing Pharmaceutical Group Co., Ltd, China who provided the study drugs and funding.

Funding

This study was supported by Chia Tai Tianqing Pharmaceutical Group Co., Ltd, China.

Author information

Author notes

  1. Jia Li and Zhixin Xue contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jia Li, Zhixin Xue, Xiaoxiang Chen & Chunde Bao

  2. Department of Rheumatology and Immunology, Tangdu Hospital of the Fourth Military Medical University (Air Force Medical University), Xi’an, China

    Zhenbiao Wu & Yan Zhang

  3. Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, Changchun, China

    Liqi Bi

  4. Department of Rheumatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China

    Huaxiang Liu

  5. Department of Rheumatology and Immunology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

    Lijun Wu

  6. Department of Rheumatology and Immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Shengyun Liu

  7. Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, China

    Xiangyang Huang

  8. Department of Traditional Chinese Medicine, Southwest Hospital, Army Medical University, Chongqing, China

    Yong Wang

  9. Department of Rheumatology, the First Central Hospital, Tianjin, China

    Wufang Qi

  10. Department of Rheumatology and Immunology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Lan He

  11. Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

    Lie Dai

  12. Department of Rheumatology and Immunology, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

    Lingyun Sun

  13. Department of Rheumatology, Anhui Provincial Hospital, Hefei, China

    Xiaomei Li

  14. Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

    Zongwen Shuai

  15. Department of Rheumatology and Allergy, Xuanwu Hospital Capital Medical University, Beijing, China

    Yi Zhao

  16. Department of Rheumatology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

    Yanyan Wang

  17. Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, China

    Jian Xu

  18. Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China

    Hao Zhang

  19. Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China

    Hao Yu

Authors
  1. Jia Li
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  2. Zhixin Xue
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  3. Zhenbiao Wu
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  4. Liqi Bi
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  20. Hao Zhang
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  21. Hao Yu
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  22. Xiaoxiang Chen
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  23. Chunde Bao
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Contributions

All authors contributed to the study design and data acquisition, The data analysis was performed by HY. JL and ZX drafted the manuscript. XC and CB revised the manuscript. The manuscript was critically reviewed by all authors for intelligent input. All authors have read the final version, approve it, and take full responsibility for the integrity of the study.

Corresponding authors

Correspondence to Xiaoxiang Chen or Chunde Bao.

Ethics declarations

Ethical standards

This study was conducted in accordance with Good Clinical Practice and Declaration of Helsinki. The study protocol was approved by the ethics committee of Renji Hospital, Shanghai Jiao Tong University School of medicine (RJLS2018-089) on Sep.7th,2018. All patients provided written Informed consent. The registration number of this study in the Chinese Clinical Trial Registry is CTR20181863.

Conflict of interest

All authors declare no competing interests.

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Li, J., Xue, Z., Wu, Z. et al. Comparison of the efficacy and safety of the adalimumab biosimilar TQ-Z2301 and adalimumab for the treatment of Chinese patients with active ankylosing spondylitis: a multi-center, randomized, double-blind, phase III clinical trial. Clin Rheumatol 41, 3005–3016 (2022). https://doi.org/10.1007/s10067-022-06199-8

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