AB0197 EFFICACY AND SAFETY OF HLX01 COMBINED WITH METHOTREXATE IN CHINESE PATIENTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAD INADEQUATE RESPONSES TO METHOTREXATE: RESULTS OF A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 3 STUDY
Authors: X. Zeng, J. Liu, X. Liu, L. Wu, Y. Liu, X. Liao, H. Liu, J. Hu, X. Lu, L. Chen, J. Xu, Z. Jiang, F. Lu, H. Wu, L. Sun, M. Wang, X. Yu, Q. Wang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rituximab is an effective therapy for rheumatoid arthritis (RA) patients with inadequate responses to methotrexate (MTX) 1, 2 . However, it has not been registered or approved in China for the treatment of RA by far. HLX01, an approved rituximab biosimilar (demonstrated in Chinese patients with diffuse large B-cell lymphoma) 3 , is thus evaluated in this study for the benefits of Chinese RA patients. Objectives: This study aimed to evaluate the efficacy and safety of HLX01 plus MTX versus placebo plus MTX in Chinese patients with active RA who had inadequate responses to MTX. Methods: This was a randomised, double-blind, placebo-controlled phase 3 study conducted in China ( NCT03522415 ). Eligible patients were randomised 2:1 to receive intravenous infusion of 2×1000 mg HLX01 or placebo on day 1 and day 15. Patients with inadequate responses at week 16 and 20 were allowed to receive rescue treatments. Patients were retreated with or switched to receive (if initially assigned to placebo) 2×1000 mg rituximab at the first day of week 24 and 26. The primary endpoint of this study was the American College of Rheumatology criteria (ACR) 20 response at week 24. Secondary efficacy endpoints were evaluated at week 12, 24, 36 and 48. The safety, pharmacokinetics, pharmacodynamics and immunogenicity of HLX01 were observed and analyzed throughout the study. Results: Between May 28, 2018 and Sep 11, 2020, a total of 275 patients (ITT set) were randomised and 263 patients without major protocol deviations were included in per-protocol set (PPS). At week 24, HLX01 showed statistically superior efficacy (p &lt;0.001) to placebo (ACR20: 60.7% vs 35.9% in ITT set, 60.3% vs 37.1% in PPS). Secondary efficacy endpoints were also significantly improved in HLX01 group compared with placebo (Table 1). The overall incidence of serious treatment emergent adverse events (TEAEs), adverse drug reactions (ADRs), and TEAEs leading to drug discontinuation were similar among treatment groups, with the most common TEAE been upper respiratory tract infection before (18.1% vs 18.5%) or after (13.0% vs 12.3%) week 24. Serum concentrations, immunogenicity and pharmacodynamics were similar between HLX01 and placebo groups. Table 1. Results of secondary efficacy endpoints at week 12, 24, 36 and 48 in ITT set. Duration Secondary efficacy endpoints ACR20 (% ) ACR50 (% ) ACR70 (% ) DAS28-CRP (mean ) HAQ-DI (mean ) HLX01 Placebo HLX01 Placebo HLX01 Placebo HLX01 Placebo HLX01 Placebo Baseline 5.49 5.43 1.40 1.45 Week 12 48.1 32.6 21.9 10.9 4.4 5.4 3.89 4.47 1.02 1.22 Week 24 60.7 35.9 36.6 18.5 15.3 12.0 3.39 4.37 0.87 1.22 Week 36 60.1 48.9 46.4 31.5 32.2 17.4 2.88 3.51 0.71 0.97 Week 48 73.8 62.0 55.2 40.2 39.9 27.2 2.82 3.51 0.72 1.03 Conclusion: Comparing with placebo plus MTX, HLX01 plus MTX showed significantly improved clinical outcomes and comparable safety profiles in Chinese patients with moderately to severely active RA who had inadequate responses to MTX, demonstrating HLX01 in combination with MTX as a well-tolerated, safe and efficient treatment option. References: [1]Emery P, Deodhar A, Rigby WF, et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab’s Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis . Sep 2010;69(9):1629-35. doi:10.1136/ard.2009.119933. [2]Rubbert-Roth A, Tak PP, Zerbini C, et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR). Rheumatology (Oxford ). Sep 2010;49(9):1683-93. doi:10.1093/rheumatology/keq116. [3]Shi Y, Song Y, Qin Y, et al. A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. J Hematol Oncol . Apr 16 2020;13(1):38. doi:10.1186/s13045-020-00871-9. Acknowledgements: The authors would like to thank participants in this study and their families. They would also like to acknowledge other investigators and staff at all clinical sites and the members of the Independent Data Monitoring Committee. Disclosure of Interests: None declared