生物类似药CT-P47与对照药托珠单抗的疗效和安全性：类风湿关节炎患者随机、活性药物对照、双盲、III期研究的1年结果
Efficacy and Safety of Biosimilar CT-P47 Versus Reference Tocilizumab: 1-Year Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study in Patients with Rheumatoid Arthritis.
作者信息
Burmester Gerd, Trefler Jakub, Racewicz Artur, Jaworski Janusz, Zielińska Agnieszka, Krogulec Marek, Jeka Sławomir, Wojciechowski Rafał, Kolossa Katarzyna, Dudek Anna, Krajewska-Włodarczyk Magdalena, Hrycaj Paweł, Klimiuk Piotr Adrian, Kim SungHyun, Suh JeeHye, Yang GoEun, Kim YunAh, Jung YooBin, Park GaHee, Smolen Josef S
机构信息
Charité - Universitätsmedizin Berlin, Berlin, Germany.
REUMA RESEARCH, Warsaw, Poland.
出版信息
Clin Drug Investig. 2025 Aug;45(8):551-563. doi: 10.1007/s40261-025-01453-8. Epub 2025 Jul 12.
BACKGROUND AND OBJECTIVE
This phase III study conducted in 22 centres in Poland assessed the efficacy equivalence of candidate tocilizumab biosimilar, CT-P47, and European Union-approved reference tocilizumab (r-TCZ) in rheumatoid arthritis. We report 1-year data, including switching from r-TCZ to CT-P47.
METHODS
This active-controlled, double-blind, multicentre trial randomised (1:1) adults (aged 18-75 years) with moderate-to-severe rheumatoid arthritis diagnosed for ≥ 24 weeks and treated with methotrextate for ≥ 12 weeks before the first study drug administration, to receive CT-P47 or r-TCZ every 4 weeks (8 mg/kg, intravenous) up to week 20. At week 24, those on CT-P47 continued maintenance treatment; those on r-TCZ were re-randomised (1:1) to continue r-TCZ (r-TCZ maintenance) or to switch to CT-P47 (CT-P47 switched) until week 48 (Treatment Period 2). After week 48, patients were followed up until week 52 (end of study). Efficacy, pharmacokinetics, safety and immunogenicity were evaluated.
RESULTS
In Treatment Period 2, 225 patients continued CT-P47 maintenance, 109 continued r‑TCZ maintenance and 110 switched to CT-P47. During Treatment Period 2, efficacy findings were comparable between groups. At week 52, the mean change from baseline in Disease Activity Score in 28 joints-erythrocyte sedimentation rate was - 4.279, - 4.231 and - 4.376 in the CT-P47 maintenance, r-TCZ maintenance and CT-P47 switched groups, respectively. Joint damage progression over 1 year was minimal in all groups. Drug serum concentrations were relatively consistent throughout Treatment Period 2. The safety profile and antidrug antibody-positive conversion rate (< 5% in each group) were similar between groups.
CONCLUSIONS
Week 52 results show maintained efficacy after switching from r-TCZ to CT-P47, and comparable efficacy, pharmacokinetics, safety and immunogenicity of CT-P47 versus r-TCZ over 1 year of treatment.
CLINICAL TRIAL REGISTRATION
NCT05489224, 24 July 2022.
背景与目的
这项在波兰22个中心开展的III期研究评估了候选托珠单抗生物类似药CT-P47与欧盟批准的对照托珠单抗（r-TCZ）在类风湿关节炎中的疗效等效性。我们报告了1年的数据，包括从r-TCZ转换为CT-P47的情况。
方法
这项活性药物对照、双盲、多中心试验将年龄在18至75岁、中度至重度类风湿关节炎诊断时间≥24周且在首次给予研究药物前接受甲氨蝶呤治疗≥12周的成年人按1:1随机分组，每4周接受一次CT-P47或r-TCZ（8mg/kg，静脉注射），直至第20周。在第24周时，接受CT-P47治疗的患者继续维持治疗；接受r-TCZ治疗的患者重新随机分组（1:1），继续接受r-TCZ治疗（r-TCZ维持组）或转换为CT-P47治疗（CT-P47转换组），直至第48周（治疗期2）。第48周后，对患者进行随访直至第52周（研究结束）。评估疗效、药代动力学、安全性和免疫原性。
结果
在治疗期2，225例患者继续CT-P47维持治疗，109例继续r-TCZ维持治疗，110例转换为CT-P47治疗。在治疗期2，各治疗组间疗效结果具有可比性。在第52周时，CT-P47维持组、r-TCZ维持组和CT-P47转换组28个关节疾病活动评分-红细胞沉降率自基线的平均变化分别为-4.279、-4.231和-4.376。所有组在1年内的关节损伤进展均最小。在整个治疗期2，药物血清浓度相对一致。各治疗组间安全性概况和抗药抗体阳性转化率（每组<5%）相似。
结论
第52周的结果显示，从r-TCZ转换为CT-P47后疗效得以维持，且在1年的治疗中，CT-P47与r-TCZ在疗效、药代动力学、安全性和免疫原性方面具有可比性。
临床试验注册号
NCT05489224，2022年7月24日。
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