一项比较英夫利昔单抗生物类似药 PF-06438179/GP1111 与参比英夫利昔单抗的随机、双盲、III 期研究：第 30 周到第 54 周的疗效、安全性和免疫原性。
Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54.
机构信息
University Medicine, Schlosspark Klinik, Berlin, Germany.
J Dietl Specialist Hospital, Krakow, Poland.
出版信息
RMD Open. 2019 Mar 28;5(1):e000876. doi: 10.1136/rmdopen-2018-000876. eCollection 2019.
OBJECTIVE
To investigate the efficacy, safety and immunogenicity of PF-06438179/GP1111 (PF-SZ-IFX) compared with European reference infliximab (Remicade; ref-IFX) in patients with moderate-to-severe, active rheumatoid arthritis after continued long-term use of PF-SZ-IFX, and in patients who were switched from ref-IFX to PF-SZ-IFX.
METHODS
REFLECTIONS B537-02 was a double-blind, active-controlled, multinational study in which patients (N=650) were initially randomised to PF-SZ-IFX or ref-IFX for 30 weeks (treatment period [TP] 1). During weeks 30-54 (TP2), the PF-SZ-IFX group (n=280) continued treatment with PF-SZ-IFX (PF-SZ-IFX/PF-SZ-IFX) and patients in the ref-IFX group (n=286) were rerandomised (1:1) to continue ref-IFX (ref-IFX/ref-IFX) (n=143) or switch to PF-SZ-IFX (ref-IFX/PF-SZ-IFX) (n=143) for a further 24 weeks. Efficacy, safety, immunogenicity and pharmacokinetics were evaluated.
RESULTS
During TP2, patients in all three treatment groups continued to maintain comparable treatment response. At week 54, the American College of Rheumatology (ACR20) response rates were 71.1% (PF-SZ-IFX/PF-SZ-IFX), 64.3% (ref-IFX/ref-IFX) and 70.6% (ref-IFX/PF-SZ-IFX). Observations for other endpoints, including ACR50/70, Disease Activity Score in 28 Joints Based on High-Sensitivity C Reactive Protein(DAS28-CRP) remission, and mean change in DAS28-CRP and Health Assessment Questionnaire-Disability Index, were also comparable. Treatment-emergent adverse events were reported in 36.8% (PF-SZ-IFX/PF-SZ-IFX), 33.6% (ref-IFX/ref-IFX) and 37.8% (ref-IFX/PF-SZ-IFX) of patients; there were no clinically meaningful differences in the safety profiles between groups. The percentage of patients who were antidrug antibody-positive was generally stable through the treatment period and comparable overall between the PF-SZ-IFX/PF-SZ-IFX (52.1%; neutralising: 80.8%), ref-IFX/ref-IFX (60.1%; neutralising: 84.9%) and ref-IFX/PF-SZ-IFX (58.0%; neutralising 78.3%) groups.
CONCLUSIONS
The similar efficacy, safety and immunogenicity of PF-SZ-IFX compared with ref-IFX were maintained for up to 54 weeks and were not affected by blinded treatment switch from ref-IFX to PF-SZ-IFX at week 30.
TRIAL REGISTRATION NUMBER
NCT02222493.
目的
评估 PF-06438179/GP1111（PF-SZ-IFX）与欧洲参考药物英夫利昔单抗（Remicade；ref-IFX）在持续长期使用 PF-SZ-IFX 后中重度、活动期类风湿关节炎患者中的疗效、安全性和免疫原性，以及在从 ref-IFX 转换为 PF-SZ-IFX 的患者中的疗效、安全性和免疫原性。
方法
REFLECTIONS B537-02 是一项双盲、活性对照、多国研究，其中患者（N=650）最初随机分为 PF-SZ-IFX 或 ref-IFX 组进行 30 周治疗（治疗期 [TP] 1）。在第 30-54 周（TP2）期间，PF-SZ-IFX 组（n=280）继续接受 PF-SZ-IFX 治疗（PF-SZ-IFX/PF-SZ-IFX），而 ref-IFX 组（n=286）患者被重新随机分配（1:1）继续接受 ref-IFX（ref-IFX/ref-IFX）（n=143）或转换为 PF-SZ-IFX（ref-IFX/PF-SZ-IFX）（n=143）再接受 24 周治疗。评估疗效、安全性、免疫原性和药代动力学。
结果
在 TP2 期间，所有三组治疗患者继续保持相似的治疗反应。第 54 周时，美国风湿病学会（ACR20）的反应率分别为 71.1%（PF-SZ-IFX/PF-SZ-IFX）、64.3%（ref-IFX/ref-IFX）和 70.6%（ref-IFX/PF-SZ-IFX）。其他终点的观察结果，包括 ACR50/70、基于高敏 C 反应蛋白的 28 个关节疾病活动度（DAS28-CRP）缓解、DAS28-CRP 和健康评估问卷残疾指数的平均变化，也具有可比性。治疗中出现的不良事件在 36.8%（PF-SZ-IFX/PF-SZ-IFX）、33.6%（ref-IFX/ref-IFX）和 37.8%（ref-IFX/PF-SZ-IFX）的患者中报告；各组之间的安全性概况无临床意义差异。在治疗期间，抗药物抗体阳性患者的百分比总体上保持稳定，且与 PF-SZ-IFX/PF-SZ-IFX（52.1%；中和：80.8%）、ref-IFX/ref-IFX（60.1%；中和：84.9%）和 ref-IFX/PF-SZ-IFX（58.0%；中和：78.3%）组之间无显著差异。
结论
PF-SZ-IFX 与 ref-IFX 的疗效、安全性和免疫原性相似，在 54 周内保持稳定，并且在第 30 周从 ref-IFX 转换为 PF-SZ-IFX 时不受影响。
试验注册
NCT02222493。
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