Scholarlink

Abstract <p>Ulcerative colitis (UC) and Crohn's disease (CD), pose a substantial burden, necessitating effective therapies. Etrolizumab, a unique monoclonal antibody targeting integrins, initially showed promise but was terminated due to lack of efficacy in PhIII studies. The immune responses elicited by patients towards etrolizumab make it a compelling subject for further in-depth investigation. This study delves into immunogenic responses to etrolizumab, examining factors contributing to such responses, including anti-drug antibody (ADA) assay format, patient baseline characteristics, immunosuppressive (IS) medication use, human leukocyte antigen (HLA) allelic expression, and the clinical impact of ADA responses on safety and efficacy endpoints. Logistic regression was used to test for association between the presence of ADA &amp; (neutralizing antibody) NAb and HLA alleles with carrier frequencies of at least 2%, alongside age, sex, and IS use. We identified two class-II HLA alleles, HLA-DQB1*06:03 and HLADQA1* 03:03, associated with the development of ADA and NAb. However, there was minimal impact of ADA on clinical parameters, such as pharmacokinetics (PK), safety, and efficacy. The findings enhance our understanding of etrolizumab immunogenicity, in the context of clinical impact, providing insights that may inform future biologic development strategies and patient selection criteria in IBD clinical trials.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Factors Impacting the Immunogenicity of Etrolizumab & Clinical Consequences

  • 期刊论文

  • 发表日期：

    2025年6月6日

查看全文
  • Gizette Sperinde,
  • Yenny Webb-Vargas,
  • Zicheng Hu,
  • Ashis Saha,
  • Christian Hammer,
  • Richard Erickson,
  • Chris Eden,
  • Deanna Galloway,
  • Rhian Jacob-Moffatt,
  • Ketevan Siradze,
  • Van Nguyen,
  • Saloumeh K. Fischer

摘要

Abstract

Ulcerative colitis (UC) and Crohn's disease (CD), pose a substantial burden, necessitating effective therapies. Etrolizumab, a unique monoclonal antibody targeting integrins, initially showed promise but was terminated due to lack of efficacy in PhIII studies. The immune responses elicited by patients towards etrolizumab make it a compelling subject for further in-depth investigation. This study delves into immunogenic responses to etrolizumab, examining factors contributing to such responses, including anti-drug antibody (ADA) assay format, patient baseline characteristics, immunosuppressive (IS) medication use, human leukocyte antigen (HLA) allelic expression, and the clinical impact of ADA responses on safety and efficacy endpoints. Logistic regression was used to test for association between the presence of ADA & (neutralizing antibody) NAb and HLA alleles with carrier frequencies of at least 2%, alongside age, sex, and IS use. We identified two class-II HLA alleles, HLA-DQB1*06:03 and HLADQA1* 03:03, associated with the development of ADA and NAb. However, there was minimal impact of ADA on clinical parameters, such as pharmacokinetics (PK), safety, and efficacy. The findings enhance our understanding of etrolizumab immunogenicity, in the context of clinical impact, providing insights that may inform future biologic development strategies and patient selection criteria in IBD clinical trials.

Graphical Abstract