Jia Li1, Zhixin Xue1, Zhenbiao Wu2, Liqi Bi3, Huaxiang Liu4, Lijun Wu5, Shengyun Liu6, Xiangyang Huang7, Yong Wang8, Yan Zhang2, Wufang Qi9, Lan He10, Lie Dai11, Lingyun Sun12, Xiaomei Li13, Zongwen Shuai14, Yi Zhao15, Yanyan Wang16, Jian Xu17, Hao Zhang18, Hao Yu19, Xiaoxiang Chen20, Chunde Bao21. 1. Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2. Department of Rheumatology and Immunology, Tangdu Hospital of the Fourth Military Medical University (Air Force Medical University), Xi'an, China. 3. Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, Changchun, China. 4. Department of Rheumatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. 5. Department of Rheumatology and Immunology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China. 6. Department of Rheumatology and Immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 7. Department of Rheumatology and Immunology, The Second Xiangya Hospital, Central South University, Changsha, China. 8. Department of Traditional Chinese Medicine, Southwest Hospital, Army Medical University, Chongqing, China. 9. Department of Rheumatology, the First Central Hospital, Tianjin, China. 10. Department of Rheumatology and Immunology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 11. Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 12. Department of Rheumatology and Immunology, Institute of Translational Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. 13. Department of Rheumatology, Anhui Provincial Hospital, Hefei, China. 14. Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 15. Department of Rheumatology and Allergy, Xuanwu Hospital Capital Medical University, Beijing, China. 16. Department of Rheumatology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China. 17. Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, China. 18. Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China. 19. Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China. 20. Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Xiaoxiang0721@126.com. 21. Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. baochunde_1678@126.com.
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.
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.
Authors: Désirée van der Heijde; Alan Kivitz; Michael H Schiff; Joachim Sieper; Ben A C Dijkmans; Jürgen Braun; Maxime Dougados; John D Reveille; Robert L Wong; Hartmut Kupper; John C Davis Journal: Arthritis Rheum Date: 2006-07