Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases.

Cover -- Table of Contents -- List of Contributors -- About the Editors -- Foreword -- References -- Preface -- 1 Disease Interception in Autoimmune Diseases: From a Conceptual Framework to Practical Implementation -- 1.1 Introduction to Disease Interception -- 1.2 Disease Interception in Autoimmune Diseases -- 1.3 Progress in Modulation of the Adaptive Immune Response in Autoimmune Inflammatory Diseases -- 1.4 The Complex Interplay between the Specificity of the Pathogenic Immune Repertoire and Its Sculpting by the Environment - Implications for Disease Interception -- 1.5 Clinical Application and Concluding Remarks -- Acknowledgments -- References -- 2 The Role of Biomarkers in Treatment Algorithms for Ulcerative Colitis (UC) -- 2.1 Background -- 2.2 Histology -- 2.3 Treatment Algorithms -- 2.4 Assessing Response to Therapy -- 2.5 Predicting Relapse -- 2.6 Summary -- References -- 3 Mechanism and Physiologically Based PK/PD Model in Assisting Translation from Preclinical to Clinical: Understanding PK/PD of Therapeutic Proteins at Site‐of‐Action -- 3.1 Introduction -- 3.2 Biologic Distribution to Tissue Site of Action -- 3.3 Target Engagement of Biologics at Site of Action -- 3.4 Translational Application of Mechanistic PBPK Modeling -- 3.5 Conclusion -- References -- 4 Application of Minimal Anticipated Biological Effect Level (MABEL) in Human Starting Dose Selection for Immunomodulatory Protein Therapeutics - Principles and Case Studies -- 4.1 Introduction -- 4.2 Safety and Immune‐Related Toxicities of Immunomodulatory Protein Therapeutics -- 4.3 Uncertainties of Toxicology Approach in FIH Safe Starting Dose Selection for Immunomodulatory Protein Therapeutics -- 4.4 Incorporating Mabel Approach in FIH Starting Dose Selection for High‐Risk Immunomodulatory Protein Therapeutics -- 4.5 Case Studies of Mabel Calculation.

4.6 Discussion and Conclusion -- References -- 5 5Model‐Based Meta‐Analysis Use in the Development of Therapeutic Proteins -- 5.1 Introduction -- 5.2 Types of MBMA and Database Considerations -- 5.3 Data Analytic Models Useful for MBMA -- 5.4 Example 1: MBMA in Inflammatory Bowel Disease -- 5.5 MBMA Literature Search -- 5.6 Kinetic‐Pharmacodynamic Models -- 5.7 MBMA Implications for Inflammatory Bowel Disease -- 5.8 Example 2: MBMA in Rheumatoid Arthritis -- 5.9 Conclusion -- References -- 6 Utility of Joint Population Exposure-Response Modeling Approach to Assess Multiple Continuous and Categorical Endpoints in Immunology Drug Development -- 6.1 Introduction -- 6.2 Latent Variable Indirect Response Models -- 6.3 Residual Correlation Modeling Between a Continuous and a Categorical Endpoint -- 6.4 Structural Correlation Modeling Between a Continuous Endpoint and a Categorical Endpoint -- 6.5 Conclusion -- References -- 7 Modeling Approaches to Characterize Target‐Mediated Pharmacokinetics and Pharmacodynamics for Therapeutic Proteins -- 7.1 Introduction -- 7.2 Target‐Mediated Drug Disposition Model -- 7.3 Data and Practical Considerations -- 7.4 What to Expect from the Concentration-Time Course -- 7.5 Approximations of the TMDD Model -- 7.6 Identifiability of Model Parameters -- 7.7 Summary -- References -- 8 Tutorial: Numerical (NONMEM) Implementation of the Target‐Mediated Drug Disposition Model -- 8.1 Introduction -- 8.2 Notations and Data -- 8.3 NONMEM Code for TMDD Model and Approximations -- 8.4 How to Select Correct Approximation -- 8.5 Numerical Implementation -- 8.6 Summary -- References -- Appendix Diagnostic Plots -- 9 Translational Considerations in Developing Bispecific Antibodies: What Can We Learn from Quantitative Pharmacology? -- 9.1 Introduction -- 9.2 Quantitative Pharmacokinetic Considerations of BsAbs.

9.3 Preclinical Considerations -- 9.4 Translational Considerations -- 9.5 Immunogenicity -- 9.6 Clinical Development of BsAbs -- 9.7 Conclusion -- References -- 10 Application of Pharmacometrics and Systems Pharmacology to Current and Emerging Biologics in Inflammatory Bowel Diseases -- 10.1 Introduction -- 10.2 Pharmacological Approaches for the Treatment of IBD -- 10.3 Mathematical Models in IBD -- 10.4 Role of FDA in the Drug Development of Biologics in the Treatment of IBD -- 10.5 Summary -- References -- 11 Pharmacokinetics‐Based Dosing for Therapeutic Monoclonal Antibodies in Inflammatory Bowel Disease -- 11.1 Inflammatory Bowel Disease -- 11.2 Population Pharmacokinetics -- 11.3 Exposure-Response -- 11.4 Exposure‐Based Dosing Strategies -- 11.5 Discussion -- References -- 12 Pharmacokinetics‐Based Dosing Strategies for Therapeutic Proteins in Inflammatory Bowel Disease -- 12.1 Introduction -- 12.2 The Need for Understanding and Controlling Variability in Exposure -- 12.3 History of Dose Individualization -- 12.4 Bayesian Methods for Dose Individualization -- 12.5 Clinical Need for Improved Dosing with mAbs -- 12.6 Expectations for Bayesian Adaptive Dosing -- 12.7 Summary and Conclusions -- References -- 13 Quantitative Pharmacology Approach to Select Optimal Dose and Study the Important Factors in Determining Disposition of Therapeutic Monoclonal Antibody in Pediatric Subjects - Some Considerations -- 13.1 Introduction -- 13.2 Pharmacokinetics of Therapeutic Monoclonal Antibody in Pediatric Population -- 13.3 Quantitative Pharmacology Considerations to Select Optimal Pediatric Dose of mAbs Based on Adult PK Studies -- 13.4 Using mPBPK Model to Study the Effects of FcRn Developmental Pharmacology on the PK of mAbs in Pediatric Subjects -- References.

14 Quantitative Pharmacology Assessment Strategy Therapeutic Proteins in Pediatric Subjects - Challenges and Opportunities -- 14.1 Introduction -- 14.2 Extrapolation of Efficacy -- 14.3 Initiation of Pediatric Trials -- 14.4 Trial Design Considerations -- 14.5 Challenges in Pediatric Trials for First‐in‐Class vs. Follow‐on Drug‐in‐Class -- References -- 15 Case Examples of Using Quantitative Pharmacology in Developing Therapeutic Proteins for Plaque Psoriasis - Guselkumab -- 15.1 Introduction -- 15.2 Understanding of Exposure-Response (ER) Relationship of Guselkumab in Psoriasis -- 15.3 Dose Selection for Guselkumab in Psoriasis -- 15.4 Quantitative Pharmacology in Post‐submission Support -- 15.5 Conclusion -- References -- 16 Vedolizumab-A Case Example of Using Quantitative Pharmacology in Developing Therapeutic Biologics in Inflammatory Bowel Disease -- Abbreviations -- 16.1 Introduction -- 16.2 Dose Selection for Adult Patients in Phase 3 Trials -- 16.3 Pharmacokinetic Profile of Vedolizumab -- 16.4 Population Pharmacokinetics in Phase 1 and 2 Trials -- 16.5 Comparison of Simulated vs. Measured Vedolizumab Trough Concentrations -- 16.6 Population Pharmacokinetics in Phase 3 Trials -- 16.7 Dose Selection for Pediatric Populations -- 16.8 Exposure-Response Analysis -- 16.9 Logistic Regression Analyses -- 16.10 Exposure-Response: Causal Inferences -- 16.11 Conclusion -- Disclosure -- References -- 17 Case Examples of Using Quantitative Pharmacology in Developing Therapeutic Proteins in Systemic Lupus Erythematosus - Belimumab -- 17.1 Introduction -- 17.2 Overview of Supporting Data and Methods -- 17.3 Body Size Characterizations and Impact on Switching from Weight Proportional to Fixed Dosing -- 17.4 The Yin and Yang of FcRn - Opposing Effect of Albumin and IgG on mAb Clearance -- 17.5 Lost in Filtration - Renal Contributions to mAb Clearance.

17.6 Conclusion -- References -- 18 Case Examples of Using Quantitative Pharmacology in Developing Therapeutic Proteins in Multiple Sclerosis - Peginterferon Beta‐1a, Daclizumab Beta, Natalizumab -- 18.1 Introduction -- 18.2 Application of Quantitative Clinical Pharmacology for Dosing Regimen Recommendation of Peginterferon Beta‐ 1a -- 18.3 Population PK/PD Analyses of Daclizumab Beta and Phase 3 Dose Selection -- 18.4 Model‐Based Approach for the Clinical Development of Subcutaneous Natalizumab -- 18.5 Summary -- References -- Index -- End User License Agreement.

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Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2024. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.