一项 3 期、随机、双盲、阳性对照临床试验，旨在比较 BAT1806/BIIB800（一种托珠单抗生物类似药）与托珠单抗参比制剂在对甲氨蝶呤应答不足的中重度类风湿关节炎患者中的疗效：治疗期 2 分析（第 24 周至第 48 周）。
A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48).
机构信息
Department of Rheumatology and Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College Hospital, Beijing, China.
Department of Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.
出版信息
Arthritis Res Ther. 2024 Sep 7;26(1):157. doi: 10.1186/s13075-024-03375-w.
BACKGROUND
Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24-48).
METHODS
In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated.
RESULTS
Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported.
CONCLUSION
In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups.
TRIAL REGISTRATION
NCT03830203 and EudraCT 2018-002202-31.
背景
在中度至重度类风湿关节炎（RA）患者中，生物类似药 BAT1806/BIIB800 与参照药物托珠单抗（TCZ）在疗效、药代动力学、免疫原性和安全性方面具有等效性，这一结果已在第 3 阶段研究的第 24 周（治疗期[TP]1）得到报告。在此，我们报告第 2 治疗期（第 24-48 周）的结果。
方法
在这项 3 期、多中心、多区域、双盲、活性对照、等效性研究中，尽管接受了甲氨蝶呤治疗但仍处于活动期的 RA 患者按 1:1:2 的比例随机分组，分别接受静脉注射 8mg/kg TCZ 每 4 周一次至第 48 周（TCZ 组），或 TCZ 治疗至第 24 周后改用 BAT1806/BIIB800 至第 48 周（TCZ 转用 BAT1806/BIIB800 组），或全程接受 BAT1806/BIIB800 治疗至第 48 周（BAT1806/BIIB800 组）。第 2 治疗期的疗效通过美国风湿病学会（ACR）缓解标准（ACR20/50/70）和疾病活动度 28 个关节评分（DAS28）自基线的变化来评估。药代动力学（谷浓度）、安全性和免疫原性也进行了评估。
结果
在 621 名随机分组的患者中，577 名（92.9%）完成了第 1 治疗期并进入第 2 治疗期（TCZ：N=145[93.5%]；TCZ 转用 BAT1806/BIIB800：N=142[92.2%]；BAT1806/BIIB800：N=290[92.9%]）。整个第 2 治疗期内，各治疗组的 ACR20 应答者比例相似（分别为第 48 周时的 87.8%、90.3%和 90.4%），ACR50 和 ACR70 应答者比例以及 DAS28 的降低也相似。各治疗组的药物谷浓度和抗药物抗体发生率相当。各治疗组的不良事件分布均衡，且无死亡事件报告。
结论
在第 2 治疗期，TCZ、TCZ 转用 BAT1806/BIIB800 和 BAT1806/BIIB800 组的疗效、安全性、免疫原性和药代动力学特征相当。
临床试验注册
NCT03830203 和 EudraCT 2018-002202-31。
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