Abstract
Drug development is a lengthy, costly process with low probability of success. Biopharmaceuticals are highly specific molecules, with efficacy and safety closely tied to target biology and pharmacology. The "learning-predicting-confirming" continuum by translational and clinical modeling and simulation (M&S) was implemented at every decision point for mavrilimumab, a human monoclonal antibody in development for rheumatoid arthritis (RA). This tutorial uses mavrilimumab as an example to demonstrate rational discovery, preclinical development, clinical study design, and dose selection of biotherapeutics by M&S.
© 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.
MeSH terms
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / pharmacokinetics
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal, Humanized
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Antirheumatic Agents / adverse effects
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Antirheumatic Agents / pharmacokinetics
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Antirheumatic Agents / pharmacology
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Arthritis, Rheumatoid / drug therapy
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Arthritis, Rheumatoid / metabolism
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Biological Products / adverse effects
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Biological Products / pharmacokinetics
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Biological Products / pharmacology*
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Drug Development / methods*
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Drug Discovery / methods*
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Humans
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Models, Biological*
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Predictive Value of Tests
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Proof of Concept Study
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
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Signal Transduction / drug effects
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antirheumatic Agents
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Biological Products
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GM-CSF receptor-alpha subunit, human
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
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mavrilimumab
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Granulocyte-Macrophage Colony-Stimulating Factor