Lena Lemke, Andrew Blauvelt, Ines Brückmann, Hillel P Cohen, Jamie Fan, Davide Guerrieri, Matej Horvat, Johann Poetzl, Claudia Torella, Qingfeng Wang, Oliver von Richter
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引用次数: 0
摘要
背景：为支持山德士阿达木单抗生物类似药（GP2017）的互换性认定，在GP2017 ADACCESS试验中评估了抗药抗体（ADA）信噪比（S/N），以直接评估免疫原性的潜在变化：ADACCESS是一项在中度至重度斑块状银屑病患者中进行的为期51周的试验，其中包括连续使用阿达木单抗参考药物（cH）治疗的患者，以及在阿达木单抗参考药物和GP2017（H2H）之间进行四次转换的患者。在切换阶段，使用电化学发光测定法每6周测量一次ADA。我们进行了非参数分析，以估计第41周时cH治疗组和H2H治疗组之间ADA信噪比差异中位数的90%置信区间（CI）。如果 90% CI 在-0.16 到 0.16 的范围内（代表检测噪音），则认为免疫原性差异无临床意义：两个治疗组在第41周和所有其他时间点的ADA信噪比差异中位数的90% CI均在-0.16至0.16的定义范围内。治疗组之间的疗效和安全性数据也相似：ADA信噪比分析表明，在阿达木单抗和GP2017之间进行最多四次切换后，免疫原性没有增加：试验注册：NCT02016105。
Comparing anti-drug antibody signal-to-noise ratios to assess immunogenicity and interchangeability in adalimumab biosimilar studies.
Background: To support an interchangeability designation for Sandoz adalimumab biosimilar (GP2017), antidrug antibody (ADA) signal-to-noise (S/N) ratios were assessed in the GP2017 ADACCESS trial to directly assess potential changes in immunogenicity.
Research design and methods: ADACCESS was a 51-week trial in patients with moderate-to-severe plaque psoriasis that included patients treated continuously with reference adalimumab (cH), and patients who experienced four switches between reference adalimumab and GP2017 (H2H). ADAs were measured every 6 weeks during the switching phase using an electrochemiluminescence assay. A non-parametric analysis was performed to estimate the 90% confidence interval (CI) of the median of difference in ADA S/N ratios between the cH and H2H treatment groups at week 41. If the 90% CI was within the margin of -0.16 to 0.16 (representing assay noise), this was considered a non-clinically meaningful difference in immunogenicity.
Results: The 90% CIs of the median of difference in ADA S/N ratios between the two treatment groups were within the defined margin of -0.16 to 0.16 at week 41, and at all other time points. Efficacy and safety data were also similar between the treatment groups.
Conclusion: Analysis of ADA S/N ratios showed no increase in immunogenicity following up to four switches between reference adalimumab and GP2017.
期刊介绍：
Expert Opinion on Biological Therapy (1471-2598; 1744-7682) is a MEDLINE-indexed, international journal publishing peer-reviewed research across all aspects of biological therapy.
Each article is structured to incorporate the author’s own expert opinion on the impact of the topic on research and clinical practice and the scope for future development.
The audience consists of scientists and managers in the healthcare and biopharmaceutical industries and others closely involved in the development and application of biological therapies for the treatment of human disease.
The journal welcomes:
Reviews covering therapeutic antibodies and vaccines, peptides and proteins, gene therapies and gene transfer technologies, cell-based therapies and regenerative medicine
Drug evaluations reviewing the clinical data on a particular biological agent
Original research papers reporting the results of clinical investigations on biological agents and biotherapeutic-based studies with a strong link to clinical practice
Comprehensive coverage in each review is complemented by the unique Expert Collection format and includes the following sections:
Expert Opinion – a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results;
Article Highlights – an executive summary of the author’s most critical points.
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