{"title":"奈莫单抗治疗结节性痒疹的药代动力学和疗效定量评价：群体药代动力学和基于模型的meta分析方法。","authors":"Tomoki Takechi, Junya Shimizu, Kenji Kabashima, Ichiro Ieiri","doi":"10.1007/s13555-025-01554-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Nemolizumab is a humanized monoclonal antibody targeting interleukin-31 receptor A. It has shown efficacy in treating patients with prurigo nodularis (PN). In this study, we characterized the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of nemolizumab in patients with PN and compared its efficacy with that of another approved treatment, dupilumab, using a model-based meta-analysis (MBMA).</p><p><strong>Methods: </strong>We updated an existing population PK (PopPK) model developed for patients with atopic dermatitis (AD) by incorporating data from four clinical studies. The updated model validated the PK of nemolizumab in patients with PN, confirming its relevance and precision. Furthermore, we developed a population PD (PopPD) model to characterize treatment response and assessed changes in the weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) over time. To conduct an MBMA, we performed a systematic literature search of public databases to identify studies for modeling the success rate of achieving a ≥ 4-point improvement in the PP-NRS and a ≥ 2-point decrease in the Investigator's Global Assessment (IGA).</p><p><strong>Results: </strong>The updated PopPK model adequately described the serum concentration profile of nemolizumab in patients with PN, suggesting a similarity in the PK characteristics between AD and PN. The PopPD model successfully described the effects of the placebo and nemolizumab on PP-NRS. Six individual randomized controlled trials were eligible for the MBMA. Model simulations indicated that the success rates for PP-NRS and IGA were consistently higher for nemolizumab compared with dupilumab, up to 24 weeks.</p><p><strong>Conclusion: </strong>The PopPK and PopPD models well described the PK and PD profiles of nemolizumab in patients with PN. MBMA demonstrated that nemolizumab was superior to dupilumab in improving response rates in patients with PN. These findings, derived from pharmacometrics modeling and indirect comparison, may help inform future clinical studies and support the ongoing evaluation of nemolizumab in PN.</p>","PeriodicalId":11186,"journal":{"name":"Dermatology and Therapy","volume":" ","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Quantitative Evaluation of Nemolizumab Pharmacokinetics and Efficacy in Prurigo Nodularis: A Population Pharmacokinetics and Model-Based Meta-analysis Approach.\",\"authors\":\"Tomoki Takechi, Junya Shimizu, Kenji Kabashima, Ichiro Ieiri\",\"doi\":\"10.1007/s13555-025-01554-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Nemolizumab is a humanized monoclonal antibody targeting interleukin-31 receptor A. It has shown efficacy in treating patients with prurigo nodularis (PN). In this study, we characterized the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of nemolizumab in patients with PN and compared its efficacy with that of another approved treatment, dupilumab, using a model-based meta-analysis (MBMA).</p><p><strong>Methods: </strong>We updated an existing population PK (PopPK) model developed for patients with atopic dermatitis (AD) by incorporating data from four clinical studies. The updated model validated the PK of nemolizumab in patients with PN, confirming its relevance and precision. Furthermore, we developed a population PD (PopPD) model to characterize treatment response and assessed changes in the weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) over time. To conduct an MBMA, we performed a systematic literature search of public databases to identify studies for modeling the success rate of achieving a ≥ 4-point improvement in the PP-NRS and a ≥ 2-point decrease in the Investigator's Global Assessment (IGA).</p><p><strong>Results: </strong>The updated PopPK model adequately described the serum concentration profile of nemolizumab in patients with PN, suggesting a similarity in the PK characteristics between AD and PN. The PopPD model successfully described the effects of the placebo and nemolizumab on PP-NRS. Six individual randomized controlled trials were eligible for the MBMA. Model simulations indicated that the success rates for PP-NRS and IGA were consistently higher for nemolizumab compared with dupilumab, up to 24 weeks.</p><p><strong>Conclusion: </strong>The PopPK and PopPD models well described the PK and PD profiles of nemolizumab in patients with PN. MBMA demonstrated that nemolizumab was superior to dupilumab in improving response rates in patients with PN. These findings, derived from pharmacometrics modeling and indirect comparison, may help inform future clinical studies and support the ongoing evaluation of nemolizumab in PN.</p>\",\"PeriodicalId\":11186,\"journal\":{\"name\":\"Dermatology and Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Dermatology and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13555-025-01554-4\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dermatology and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13555-025-01554-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Quantitative Evaluation of Nemolizumab Pharmacokinetics and Efficacy in Prurigo Nodularis: A Population Pharmacokinetics and Model-Based Meta-analysis Approach.
Introduction: Nemolizumab is a humanized monoclonal antibody targeting interleukin-31 receptor A. It has shown efficacy in treating patients with prurigo nodularis (PN). In this study, we characterized the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of nemolizumab in patients with PN and compared its efficacy with that of another approved treatment, dupilumab, using a model-based meta-analysis (MBMA).
Methods: We updated an existing population PK (PopPK) model developed for patients with atopic dermatitis (AD) by incorporating data from four clinical studies. The updated model validated the PK of nemolizumab in patients with PN, confirming its relevance and precision. Furthermore, we developed a population PD (PopPD) model to characterize treatment response and assessed changes in the weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) over time. To conduct an MBMA, we performed a systematic literature search of public databases to identify studies for modeling the success rate of achieving a ≥ 4-point improvement in the PP-NRS and a ≥ 2-point decrease in the Investigator's Global Assessment (IGA).
Results: The updated PopPK model adequately described the serum concentration profile of nemolizumab in patients with PN, suggesting a similarity in the PK characteristics between AD and PN. The PopPD model successfully described the effects of the placebo and nemolizumab on PP-NRS. Six individual randomized controlled trials were eligible for the MBMA. Model simulations indicated that the success rates for PP-NRS and IGA were consistently higher for nemolizumab compared with dupilumab, up to 24 weeks.
Conclusion: The PopPK and PopPD models well described the PK and PD profiles of nemolizumab in patients with PN. MBMA demonstrated that nemolizumab was superior to dupilumab in improving response rates in patients with PN. These findings, derived from pharmacometrics modeling and indirect comparison, may help inform future clinical studies and support the ongoing evaluation of nemolizumab in PN.
期刊介绍：
Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers.
The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.
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