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<p>This study aimed to establish an exposure-response model for IL-17&#xa0;A inhibitors to predict the clinical efficacy of novel agents based on in vitro potency and pharmacokinetic parameters, guiding the development of new IL-17&#xa0;A-targeting therapies.&#xa0;A systematic literature search was conducted in PubMed, Cochrane Library, and Embase to identify randomized controlled trials of three FDA-approved IL-17&#xa0;A inhibitors: secukinumab, ixekizumab, and bimekizumab. Primary endpoints included PASI 75 and PASI 90. Pharmacokinetic parameters were extracted from FDA and EMA review documents, while the half-maximal inhibitory concentration (IC<sub>50</sub>) values came from published studies. An exposure-response model was developed to characterize treatment effects in moderate-to-severe plaque psoriasis and externally validated using clinical data of xeligekimab.&#xa0;A total of 30 clinical trials involving 12,491 subjects were included. The model accurately described the time-effect characteristics of the PASI 75/90 response rates of the three IL-17&#xa0;A inhibitors. Average drug concentration (C<sub>av</sub>) was the most relevant exposure metric. The IC<sub>50</sub> value significantly influenced exposure-response outcomes, and lower IC<sub>50</sub> values required lower C<sub>av</sub> for comparable efficacy. External validation showed high predictive accuracy for xeligekimab. A reference table was also constructed to estimate required doses based on IC<sub>50</sub> and desired therapeutic targets, facilitating rational dose selection.&#xa0;Based on existing pharmacokinetic and clinical efficacy data of IL-17&#xa0;A inhibitors, this study successfully developed a streamlined and accurate exposure-response model, offers a practical tool for efficacy prediction and dose optimization in the development of novel agents targeting IL-17&#xa0;A.</p>

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Model-Based Meta-Analysis of IL-17 A Inhibitors for Moderate-to-Severe Plaque Psoriasis: Establishing Exposure-Response Relationships to Inform Targeted Drug Development

  • 期刊论文

  • 发表日期：

    2026年1月16日

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  • Yixiao Liu,
  • Xiaoya Chen,
  • Ling Xu,
  • Qingshan Zheng,
  • Lujin Li

摘要

This study aimed to establish an exposure-response model for IL-17 A inhibitors to predict the clinical efficacy of novel agents based on in vitro potency and pharmacokinetic parameters, guiding the development of new IL-17 A-targeting therapies. A systematic literature search was conducted in PubMed, Cochrane Library, and Embase to identify randomized controlled trials of three FDA-approved IL-17 A inhibitors: secukinumab, ixekizumab, and bimekizumab. Primary endpoints included PASI 75 and PASI 90. Pharmacokinetic parameters were extracted from FDA and EMA review documents, while the half-maximal inhibitory concentration (IC50) values came from published studies. An exposure-response model was developed to characterize treatment effects in moderate-to-severe plaque psoriasis and externally validated using clinical data of xeligekimab. A total of 30 clinical trials involving 12,491 subjects were included. The model accurately described the time-effect characteristics of the PASI 75/90 response rates of the three IL-17 A inhibitors. Average drug concentration (Cav) was the most relevant exposure metric. The IC50 value significantly influenced exposure-response outcomes, and lower IC50 values required lower Cav for comparable efficacy. External validation showed high predictive accuracy for xeligekimab. A reference table was also constructed to estimate required doses based on IC50 and desired therapeutic targets, facilitating rational dose selection. Based on existing pharmacokinetic and clinical efficacy data of IL-17 A inhibitors, this study successfully developed a streamlined and accurate exposure-response model, offers a practical tool for efficacy prediction and dose optimization in the development of novel agents targeting IL-17 A.